ATTACHMENT A
DESIGNER SELECTION– MAIN CAMPUS ELECTRIC INFRASTRUCTURE ADDITIONS
This project provides new underground, medium voltage electrical (15kV) and telecommunications ductbanks at three separate locations on main campus: • South Columbia Street Crossing Ductbank • South Road and Stadium Drive Ductbank • Ductbank Reconfiguration at UNC Women & Children’s Hospital
The total project budget is $1.6M with funding by Energy Services receipts.
This project was advertised on October 19, 2011. Nine (9) proposals were received.
Four (4) firms were interviewed on December 7, 2011. Members of the Board of Trustees did not participate in the interviews.
The committee recommended the selection of three firms in the following priority order: 1. RMF Engineering, Inc., Raleigh, NC 2. Affiliated Engineers, Inc., Chapel Hill, NC 3. United Engineering Group, Inc., Raleigh, NC
The firm in the number one position, RMF Engineering, Inc., was recommended because of the strength of its team and its recent and relevant experience.
RECOMMENDED ACTION
A motion to approve the three firms in the above priority order.
FACILITIES PLANNING DEPARTMENT THE UNIVERSITY John D. Masson, Project Manager of NORTH CAROLINA 103 AIRPORT DRIVE £It CHAPEL HILL TEL: 919-962-7019 CAMPUS BOX 1090 FAX: 919-962-9103 CHAPEL HILL, NC 27599-1090 www.fpc.unc.edu
MEMORANDUM
TO: File FROM: John Masson DATE: December 2] , 201 1 RE: Main Campus Ductbank Improvements Consultant Selection
The University's Energy Services Department recently identified the need for a project to design and construct new medium voltage electrical and telecommunications infrastructure at three separate locations on the UNC-Chapel Hill main campus to correct basic system deficiencies. The scope of the project includes the installation of approximately 1,345 I ineal feet of new underground ductbank constructed in various conduit configurations, the installation of at least three underground vaults, and the installation of at least one switch pad.
A budget of $1,590,000 has been established for the project and Energy Services has committed funds from the Utilities Trust Fund to cover the cost of the study. Planning for the project has been authorized and the need for engineering consulting services was advertised on the UNC-General Administration site (under the Designer Solicitations link) on Wednesday, October 19, 2011.
Nine (9) letters of interest and designer qualification packages were received on or before the submission deadline ofNovember 8, 2011.
A pre-selection/short-listing committee was made up of the following UNC-CH personnel:
Ray DuBose, Energy Services Director Gaylan Bishop, Electric Distribution Systems Manager Wayne Sink, Electric Distribution Systems Engineer Phil Mazarick, Electric Distribution Design Technician John Masson, Facilities Planning Department Project Manager
The pre-selection committee reviewed the designer supplied information, both individually and collectively, and on November 16, 2011, the group met to develop the interview short-I ist. The following four (4) consulting engineering firms were selected for interviews:
• Affiliated Engineers, Inc., Chapel Hill, NC • Jacobs Engineering Group, Inc., Cary, NC • RMF Engineering, Inc., Raleigh, NC • United Engineering Group, Inc., Raleigh, NC MEMO TO: File December 21, 201 1 Page 2 of2
The pre-selection committee chose the short-listed firms based upon recent and related project experience as documented by their submitted qualification and credentials information (i.e. SF-254 fonns). The committee was especially interested in interviewing firms that had a strong combination of demonstrated expertise and recent, pertinent experience with medium voltage, electrical infrastructure and distribution projects.
On Wednesday, December 7,20 II, interviews were held in the C-Red Conference Room at the Energy Services Administration Building, beginning at 10:00AM and ending at 3:20PM. The interview committee was comprised of the following University personnel: Gaylan Bishop, Wayne Sink, Phil Mazarick and John Masson. Representatives from the University's Construction Management Office and Historically Underutilized Business office were invited to participate but did not.
After hearing all of the designer presentations and considering the infonnation provided regarding qualifications, credentials, design expertise and relevant experience, the committee recommends the following finns in priority order:
1. RMF Engineering, Inc., Raleigh, NC 2. Affiliated Engineers, Inc., Chapel Hill, NC 3. United Engineering Group, Inc., Raleigh, NC
For this project, the selection committee found the number one recommended firm to have:
(1) Current, very successful ductbank project work experience at UNC-Chapel Hill (2) Excellent recent experience with underground electrical distribution systems of various voltages (3) Demonstrated a practical design approach using AutoCAD Civil 3D design software (4) Emphasized the importance of using cable pulling software in the ductbank design process (5) Recent experience on numerous State ofNorth Carolina projects (6) Recent and extensive work experience at other local university sites (7) Enthusiastically cited the challenges associated with this project and a strong desire to work on them (8) The best overall team to meet project requirements (9) Local presence
It is recommended that the committee's recommendation be carried forward to the University's Board of Trustees at their next regularly scheduled meetings for final consideration and designer selection. All procedures set forth in the State Construction Manual relating to designer selections were followed in making these recommendations.
The letter of interest and the proposed design team infonnation from the number one recommended firm is attached. All other infonnation pertinent to this selection will be kept by the Facilities Planning project manager. Should there be any questions about this matter, John Masson (the writer of this memo), can be contacted at 962-7019.
Attachments ~ . ~ r L " . , 1'"_,,
November 8, 2011
The University ofNorth Carolina at Chapel Hill Facilities Planning Department Giles F. Homey Building Campus Box 1090 103 Airport Drive (27516) Chapel Hill, NC 27599
Attention: Mr. John Masson
Reference: Main Campus Ductbank Improvements
Dear Mr. Masson:
We are very excited about the opportunity to continue working with you personally and the UNC Chapel Hill team on the Main Campus Ductbank Improvements project.
Our team has very much enjoyed overcoming the challenges associated with the Carolina North Campus Ductbank project and, if selected, will bring the same level of energy, passion, and expertise on this project as well. We recognize the importance of the role strong infrastructure systems play in allowing the university to fulfill its mission and appreciate working with an owner's team which values proactive thinking and getting all ofthe details right.
The most enticing part of the RFP was the statement that "This project is going to be a challenge. Innovative installation methods/techniques are weLcomed!" Our team lives for challenging campus utility installations. We pioneered the use of 3D civil designs for just this very case. In addition, we have utilized just about every type of installation technique available. We can bring multiple options to solving complex utility installation challenges and communicate them in a way that the university's team can quickly identify the best option ofthe particular situation.
John, if you need any additional information, please do not hesitate to contact me at (919) 941-9876. Sincerely,
RMF ENGINEERING, INC.
J. Tim Griffin, PE, CBCxP, CEM, LEED AP Principal
RMF ENGINEERING, INC. 8081 AReo C ORPORATE D RIVE SUITE 300 RALEIGH, N OR TH CAROLINA 27617 PHONE : 919-941-9876 FAX: 919-941-9957 RMF Engineering, Inc.
I. PROPOSED DESIGN TEAM FOR THE PROJECT
For this particular project, we are proposing a design team that has a tremendous familiarity with UNC-Chapel Hill. We believe that our group, led by Greg Carnathan, PE, will give you the best options moving forward. As you know, our design team members are well-qualified and experienced personnel in the evaluation, design and operations of various facilities. RMF's personnel will be committed to the contract, ensuring a high level of technical insight and quality. It is guaranteed and can be included in the engineering contract that all proposed core design team members will be continuously available during the entire duration of the project. This project will have a high priority with our firm. The loss of a key person due to unforeseen circumstances will be immediately filled with a person of equal or greater qualifications. Any team substitution not initially envisioned will be proposed for acceptance before assigning to the project management team.
The following team members have been established for the Ductbank Improvements project. Resumes for key tea~ members are on the following pages.
• Tim Griffin, PE, CBCxP, CEM - Principal In Charge • Greg Carnathan, PE, CEM - Project Manager/Mechanical Engineer • Cheryl Piner, PE - Civil/Structural Engineer • Vance Nail, PE - Quality Control/Civil Engineer • Mark Demana, PE - Electrical Engineer • Kyle Bowker, EI - Civil Designer
Lappas and Havener, PA, will provide landscape architecture as needed for our team. Their 254 is included at the end of this proposal.
Submittal Criteria ATTACHMENT B
CONSTRUCTION MANAGER AT RISK SELECTION– CAROLINA NORTH INFRASTRUCTURE AND RESEARCH BUILDING
This project is for the initial development on the Carolina North campus and includes a 225,000 SF building to house interdisciplinary research groups, campus infrastructure and a small central utility plant.
The combined project budget is $72.5M with funding by the University.
This project was advertised on November 23, 2011. Sixteen (16) proposals were received. Six (6) firms were interviewed on January 18, 2012. Members of the Board of Trustees did not participate in the interviews.
The committee recommended the selection of three firms in the following priority order: 1. Skanska USA Building, Inc./Horus Construction Services Durham. NC 2. Lend Lease with Parker Construction Group Durham, NC 3. DH Griffin /Balfour Beatty Raleigh, NC
The firm in the number one position, Skanska USA Building, Inc., was recommended because of the strength of its team and its recent and relevant experience.
RECOMMENDED ACTION
A motion to approve the three firms in the above priority order.
SKANSKA mqill£i RE r: E 1\' r: [)
~f " . '.. ' , December 14,2011 . ! L,. , l , '1 1: 10 4309 Emperor Blvd., Suite 200 Durham, North Carolina 27703 919.941.7900 phone 919.941.0159 fax Diane Gillis VWV\III.usa .skanska .com Facilities Planning Department University of North Carolina at Chapel Hill CB 1090, Giles F. Horney Building 103 Airport Drive Chapel Hill, North Carolina 27599-1090
On behalf of Skanska USA Building Inc. and Horus Construction Services, a 100 percent African-American owned firm and a 20 percent partner on this project, we are pleased to submit this proposal for construction management at risk services for the above referenced project. As you review our executive summary and proposal, you will see that we have worked diligently to understand the objectives and importance the Research Building and Infrastructure project and how it will impact the future development of Carolina North. As one of the leading providers of construction services here in the Triangle area and having served UNC-Chapel Hill for nearly 10 years, we are quite confident of our ability to provide the kind of innovative services needed for this landmark project. As you review our proposal, please keep the following key factors in mind:
1. Our proposed team has been working together on signature building, infrastructure, and utility projects for nearly seven consecutive years. The team has delivered projects for Duke University and NC State University during their time together that included major research and integrated science facilities, campus infrastructure and central utility plant construction. Their experience and passion for construction, collaboration and client service make them ideal for this project.
2. The Research Building project will require a construction manager who is experienced in building, infrastructure and utility plant construction. Locally and regionally, we have recently completed and are currently involved with major projects for UNC Hospitals, Rex Hospital, and NC State that included all of these components. The experience gained and lessons learned from these projects will assure UNC-Chapel Hill that we bring the broad expertise needed to properly provide preconstruction and construction service.
3. Carolina North is planned to be a model in sustainable development. As the first construction firm in the U.S. to achieve ISO 14001 status for our commitment to environmental responsibility, Skanska has completed over 20 projects locally that have achieved LEED® certification. Additionally, we are committed to moving our industry and practices toward "deep green" - a recognition that we can and must do more than just comply with minimum environmental standards. Our teams look for innovative ways to assist our clients in moving projects towards innovative technologies and strategies to minimize environmental impacts of the project.
( Oll'>tr Li etUJf1 I\rtd!klC)lil dlllhK [01 (.11 util i. I Nor til He',('tHdl 81lltdll H) LII Hili Ifr .J')llll( Hili' 4. Understanding that the Carolina North Campus development and this project will involve sensitive wetland areas, we have chosen to include SEPI Engineering, a 100 percent female owned engineering firm, as our environmental and wetlands consultant. Through their vast experience in dealing with wetland considerations, we believe they will bring significant added value to our preconstruction, planning and construction services.
5. Led by our staff diversity coordinator, our project teams have implemented one of the most effective, recognized and helpful HUB programs in the State. Our teams work tirelessly to identify existing and new minority resources, develop capacity and expertise within those firms, create opportunities for success and assist those firms in achieving their own business goals. While our numbers are outstanding, we are most proud of the trust, confidence, and relationships we have built within the HUB community. These relationships will lead to more success at UNC-Chapel Hill.
We hope you find our proposal convincing and look forward to having the opportunity to present our team, experience and project approach to your selection committee in the near future. In the meantime, should you have any questions or need additional information, please do not hesitate to contact me.
Sincerely, Skanska USA Building Inc. Horus Construction Services
\\~~~
Randy McNeely, LEED AP Jonathan Graham Senior Vice President President
(c)ll',IIII( 111111 M.lIl. II lei .11 IIll,k 101 ( ell I Jlilld [\JOII I I r Section 2. Project Experience A-G. List three projects of similar size, scope and complexity performed by the proposer and additional relevant project information. We Build More Than Buildings needed to assure that all components of your This project is unique in that it combines three project are planned and managed properly. distinctly different components - a research Our three most relevant projects are local building, infrastructure, and a central utility plant. and have been or are currently being built Having a construction manager who understands by our proposed project learn. Our team the unique aspects of each of these components is will bring direct knowledge and expertise important for success, and Skanska Horus has that from these projects which will benefit the broad background of experience. Carolina North Research Building and From a building standpoint, our local office is Infrastructure project. the leader in the delivery of academic research Our three most relevant projects are: facilities in the Triangle, having successfully put in place over one million square feet of similar North Carolina State University building construction on the UNC, Duke and Engineering Building III, CUP Upgrades, NC State campuses. Our proposed project team Infrastructure and Parking Garage has managed major infrastructure projects at NC State's Centennial Campus, and our office is North Carolina State University currently building UNC Hospitals' Hillsborough James B. Hunt Library, Infrastructure and Campus which includes major infrastructure for a Parking Garage brand new campus. In addition, we have access to resources from our national civil group should the Duke University need arise. Fitzpatrick Center for Interdisciplinary Engineering, Medicine, and Applied Sciences And, finally, we have recently completed central utility facilities at Duke University and NC State and are currently involved with similar facilities for UNC Hospitals' Hillsborough Campus and Rex Hospital. Our team brings the diverse knowledge ('ull"llll( 11!)[1 [\I].111.1W·' 111{IS~' for ( tliCllill,1 NOIlil I{l,.,t'l·,Jr.ll Blllltill Iq .II Id Ii If I d':>lIllt. 1I11(' l "{'(Iinl') 1'1 (lil , Il: Proposed Team Experience Project Relevance • Randy McNeely • Dave Johnson • Infrastructure and site work • Completion of student • Tom Hyzak • Terry Rowe • Seeking LEED ® Silver green space certification • Mark Collins • Melanie Moreschi • Multiple designers • Stream restoration • State construction • Cathy Howell • Don Davis • Innovative, flexible creativity • Construction management • Joan Hooks • Dick Cecich studios at risk • Fred Donaldson • Bioretention Designed by world-renowned architect Snohetta, the library beams, heat recovery, radiant cooling and heating ceiling Client Preconstruction will anchor the south side of the campus oval and provide the panels; and solar panels that will provide hot water for the NC State University Services building. The building is expected to achieve LEED@Silver Full Scope critical link between the campus and the future Town Center. Architect The 220,OOO-SF building will house both the Centennial certification. Snohetta, Pearce Brinkley Cease + Lee, Number of days Campus library and the Institute for Emerging Issues, a As part of this project, the nearby stream, which runs Affiliated Engineers allocated think tank that convenes leaders from business, nonprofit approximately 17S-LF, required extensive restoration. To and RMF Engineering 1097 organizations, government and higher education. make this area of campus more user-friendly and improve GMP Number of days appearance, the stream bed had to be elevated. During the $95,200,000 taken The facility will incorporate a two million volume automated On schedule for 1097 book retrieval system in lieu of typical library stacks. There elevation process, under-drain pipe and liners were added Size days 220,000-SF will also be spaces for student study and research, including to channel water and prevent erosion below the stream, As requested, please Creativity Studios which feature a "black-box" design with ensuring that the environment above the liner remains Delivery Method see owner references conducive for existing species. It was also essential to keep the Construction in Appendix A revolving walls, sliding screens, write-on surfaces, moveable management at risk projectors, surround sound, portable seating and curtain stream in the exact same horizontal alignment. Completion Date track and panels to encourage collaborative work and September 2012 The project also includes a $7 million, 600-space pre-cast brainstorming sessions. Teaching and Visualization Labs parking deck, infrastructure utilities that will serve future further encourage creative and innovative teaching methods buildings on campus, and the completion of the pedestrian with real-time capture and broadcast and simultaneous oval, the centerpiece of the Centennial Campus Master plan. multi-source display which will allow for command and control room simulation and large-scale ultra HD/3-D visualization. The project incorporates a green roof; a highly efficient heating, piping and air conditioning system using chilled (uII,>IIlI(lll.l!l M,llJ.lfjPI ':JL'(.IIUI12. Illujt.'r. l L:-q 1("1 IC,!I ICI ' Page 8 ATTACHMENT D 11. Finley Golf Course Club House Addition - $3,500,000 (Funding – Gifts) Construction began September 2011 and is 17% complete. Project completion is expected in October 2012. 12. Electrical Infrastructure Additions (Phase I) -$8,025,000 (Funding – University Non-Appropriated/Receipts) Construction began August 2011 and is 55% complete. Project completion is expected in August 2012. 13. Frank Porter Graham Student Union - Renovation - $7,500,000 (Funding – Gifts) Construction began August 2011 and is 25% complete. Project completion is expected in August 2012. 14. Brinkhous Bullitt Exterior Repairs - $300,000 (Funding – University Non-Appropriated/Receipts) Construction began November 2011 and is 17% complete. Project completion is expected in April 2012. 15. Morehead-Cain Foundation - $2,000,000 (Funding – Gifts) Construction began June 2011 and is 95% complete. Project completion is expected in January 2012. PROJECTS IN DESIGN: 1. Morehead Planetarium Addition and Renovation - $58,000,000 (Funding – State Appropriation/Gifts) Project has been approved to bid and has Site Development Permit from Town of Chapel Hill. Project is on hold pending construction funding. 2. Bingham Facility – $14,700,000 (Funding – University Non Appropriated) Construction documents for wastewater treatment facility are approved. Bid date will be scheduled after public hearing on the draft of the wastewater treatment permit conducted by N.C. Department of Environment and Natural Resources. 3. Electric Infrastructure Additions - $15,000,000 (Funding – University Non-Appropriated/Receipts) Bids for Phase 2 will be received in February, 2012. 4. Alternative/Renewable Energy Study – Phase I - $5,300,000 (Funding – University Non-Appropriated/Receipts) Construction contract for Landfill Gas Phase 2 pipeline is in process. Climate action plan update is underway for fuel sources. 5. School of Law at Carolina North - $5,500,000 (Funding – State Appropriation) Designer selected in November, 2008. Project is waiting design funding. 6. Carolina North Infrastructure – Phase I - $7,200,000 (Funding – University Non-Appropriated) Concept plan was submitted and the Energy/Water analysis is underway. CM at Risk selection scheduled for January, 2012 Board of Trustees meeting. 7. Old Sanitary Landfill Remediation at Carolina North - $500,000 (Funding – State Appropriation) Designer selected in November, 2008. Project is waiting design funding. 8. Railroad Sidings - $3,000,000 (Funding – University Non-Appropriated) The programming and site feasibility report is complete. Status of Capital Improvement Projects Page 2 January 1, 2012 ATTACHMENT D 9. South Columbia Road Improvements - $1,400,000 (Funding – University Non-Appropriated) The construction schedule for the Phase III improvements south of Health Sciences Library is being coordinated with the schedule of the NCDOT South Columbia Road improvement project. 10. Rizzo Center Phase III - $36,000,000 (Funding – Gifts) Design Development documents is underway. Special Use Permit application will be submitted in January, 2012. 11. Renovations to Mary Ellen Jones Building - $32,000,000 (Funding – University Non-Appropriated) Schematic design is complete and project is on hold waiting funding. 12. Medical Education Building - $1,000,000 (Funding – University Non-Appropriated) Designer has prepared options and cost estimates for School of Medicine. Project is waiting design funding. 13. Carrington Hall Renovation - $250,000 (Funding –Repair and Renovations) Programming study is complete and project is waiting design funding. 14. Student Recreation Center and Fetzer Gymnasium Roof Replacement - $2,900,000 (Funding – Repair and Renovations) Construction documents are complete and in review. Project is waiting construction funding. 15. Knapp – Sanders Hall Second and Third Floor HVAC Replacement Study - $600,000 (Funding – Repair and Renovations) Construction documents are complete and project is waiting construction funding. st nd 16. Davis Library – 1 and 2 Floor renovations -$450,000 (Funding – Repair and Renovations) Programming is complete and project is waiting construction funding. 17. Davis Library Elevator Renovation - $1,100,000 (Funding – Repair and Renovations) Combined Schematic Design/Design Development documents are complete. Project is on hold waiting construction funding. 18. Kenan Laboratories Renovations - $1,900,000 (Funding- University Non-Appropriated) Construction documents have been submitted for review. Estimated bid date is January, 2012. 19. Thurston Bowles Third Floor Renovation - $1,200,000 (Funding – University Non-Appropriated) Combined schematic design/design development package has been submitted for review. Estimated bid date is April, 2012. 20. Craige Deck Expansion - $24,000,000 (Funding – University Non-Appropriated) Combined schematic design/design development phase is underway. Estimated bid date is September, 2012. 21. Friday Center Chiller Replacement - $2,700,000 (Funding – University Non-Appropriated) Construction contracts are in process. 22. Brauer Hall Renovations - $4,800,000 (Funding – University Non-Appropriated) Combined Programming and Concept design has been submitted for review. Status of Capital Improvement Projects Page 3 January 1, 2012 ATTACHMENT D 23. Davis Library Renovations to House Odum Institute - $500,000 (Funding – University Non-Appropriated) Programming is in process to renovate second, third and fourth floors to relocate the Odum Institute from Manning Hall. 24. Manning Substation Addition - $3,000,000 (Funding – University Non-Appropriated) Combined Schematic Design/Design Development is in progress. 25. Carolina North Research Building - $67,000,000 (Funding – University Non-Appropriated) Programming is in process. CM at Risk selection scheduled for January, 2012 Board of Trustees Meeting. 26. Lighting Upgrades for Parking Decks - $1,500,000 (Funding – University Non-Appropriated) Designer fee proposal is pending. 27. Main Campus Electric Infrastructure Additions - $1,600,000 (Funding – University Non-Appropriated) Designer selection scheduled for January, 2012 Board of Trustees meeting. 28. Performance Contracting - $20,000,000 (Funding – University Non-Appropriated) Advertised for Energy Services Companies in November, 2011. Proposals are February 15, 2012. Status of Capital Improvement Projects Page 4 January 1, 2012 ATTACHMENT D SUMMARY OF MAJOR CAPITAL IMPROVEMENT ACTIVITY: No. of Projects Dollar Value Completed since 7/2011 10 $ 90,849,776 Under Construction 15 $ 742,125,823 In Design 28 $ 313,100,000 HISTORICAL RECORD OF ACTIVITY: UNDER CONSTRUCTION IN DESIGN Date No. of Projects Dollar Value No. of Projects Dollar Value Dec. 1983 10 $ 62,326,000 8 $ 18,645,000 Jun. 1984 10 $ 66,858,320 11 $ 14,956,950 Oct. 1984 13 $ 77,924,820 16 $ 28,455,450 Jun. 1985 15 $ 75,753,450 18 $ 57,302,500 Feb. 1986 13 $ 67,684,000 30 $190,990,620 Aug. 1986 11 $ 61,093,000 25 $191,213,620 Feb. 1987 14 $ 39,924,000 27 $183,061,220 Aug. 1987 13 $ 26,817,520 25 $210,316,100 Feb. 1988 12 $ 42,354,520 26 $222,477,900 Aug. 1988 14 $ 61,721,870 34 $254,328,430 Feb. 1989 15 $157,882,770 40 $168,321,630 Aug. 1989 20 $158,003,370 29 $170,550,730 Feb. 1990 18 $153,331,770 34 $174,785,500 Aug. 1990 14 $161,479,980 29 $165,398,600 Feb. 1991 10 $191,489,780 26 $147,486,500 Aug. 1991 11 $202,564,380 28 $132,000,800 Jan. 1992 9 $193,656,480 31 $123,015,800 Aug 1992 16 $196,850,380 25 $132,470,400 Jan 1993 15 $178,790,400 27 $137,062,000 July 1993 9 $ 91,072,000 21 $121,141,100 Jan 1994 6 $ 90,707,300 33 $154,615,300 July 1994 15 $101,999,300 28 $147,370,700 Jan 1995 13 $ 66,320,700 52 $175,385,600 July 1995 14 $101,192,800 46 $164,311,800 Jan 1996 11 $ 89,901,800 67 $246,980,600 July 1996 17 $ 92,701,100 61 $299,168,300 Jan. 1997 19 $131,072,400 63 $282,872,700 July 1997 37 $235,425,600 44 $223,235,350 Jan 1998 33 $158,837,100 50 $278,691,575 July 1998 36 $183,705,300 43 $285,946,375 Jan 1999 26 $153,298,200 42 $314,955,275 July 1999 20 $175,689,300 44 $374,499,175 Jan 2000 18 $173,787,000 38 $380,677,875 July 2000 20 $171,732,100 44 $402,994,475 Jan 2001 20 $265,311,575 56 $255,342,400 July 2001 30 $277,577,875 57 $509,245,260 Jan 2002 28 $282,315,475 51 $533,569,700 July 2002 25 $297,186,000 51 $533,569,700 Jan 2003 18 $246,220,200 52 $700,266,390 July 2003 15 $239,095,165 58 $677,135,478 Jan 2004 18 $345,073,797 59 $607,602,868 July 2004 24 $435,597,765 61 $837,011,823 Jan 2005 32 $540,484,649 77 $997,282,175 July 2005 42 $604,951,066 62 $848,018,466 Jan 2006 39 $606,059,278 50 $681,154,808 July 2006 36 $753,387,157 55 $697,916,808 Jan 2007 39 $493,513,761 60 $729,086,980 July 2007 38 $559,519,076 50 $586,321,980 Jan 2008 29 $510,723,322 46 $733,693,000 July 2008 27 $570,815,114 51 $715,328,000 Jan 2009 25 $429,973,546 47 $906,213,000 July 2009 24 $633,089,281 40 $577,740,422 Jan 2010 18 $600,252,605 22 $409,120,032 July 2010 18 $618,429,022 32 $539,620,032 Jan 2011 15 $605,745,206 30 $474,190,032 July 2011 19 $802,905,823 28 $292,000,000 Jan 2012 15 742,125,183 28 $313,100,000 During the same period we have completed 465 major capital improvement projects with a total in-place cost of $2,856,773,346. Status of Capital Improvement Projects Page 5 January 1, 2012 Review of the Types of Leases Held by The University of North Carolina at Chapel Hill I. Lease Acquisitions (Space Leased to the University by Others) A. Office Space Leases · 398,895 square feet of office space leased to the University with annual rent payments of $7,741,449.74 (representing 1.18% decrease in leased square feet and 0.50% decrease in annual rent payments since the last lease report in July, 2011) · 63,471 square feet of office space (included in the above-referenced 398,895 square feet) leased to the University in Endowment Owned Buildings with annual rent payments of $1,237,684.50 (representing no change in leased square feet or annual rent payments since last lease report in July, 2011) B. Miscellaneous Leases · Leases to the University with annual rent payments of $32,540.94 (representing 1.6% increase in annual rent payment since the last lease report in July, 2011) C. Storage Space Leases · 2,560 square feet of storage space leased to the University with annual rent payments of $13,952.00 (representing 62.06% decrease in leased square feet and 60.34% in annual rental payments since the last lease report in July, 2011) II. Lease Dispositions (Space Leased by the University to Others) A. Rental Houses · 21 houses (18 leases) with projected annual rent receipts of $242,702.00 (representing a 10.51% decrease in annual rent receipts since the last lease report in July, 2011) B. Rental Buildings · 2 buildings with annual rent receipts of $5,409,721.00 (representing no change in annual rent receipt since the last lease report in July, 2011) C. Land Leases · 81.41 acres of land leased with nominal rent receipts (representing no change in land leased or change in nominal annual rent receipt since the last lease report in July, 2011) Page 2 The University of North Carolina at Chapel Hill Office Space Leased to UNC-CH Chapel/Hill Carrboro As of January 1, 2012 Lessee Lease End Owner/Lessor Lessee Division Department Funding Source Location Sq Ft Annual Rent $ Per Sq Ft Renewal Options Classification Date 1 West Franklin Preservation LP Health Affairs Carolina Population Center Research Program Overhead Receipts 206 W Franklin St Mth to Mth 1,871 $ 34,052.20 $ 18.20 None 2 West Franklin St. Preservation Limited Health Affairs Carolina Population Center Research Program Overhead Receipts 206 W. Franklin St Mth to Mth 8,607 $ 156,647.40 $ 18.20 None 3 Franklin Street Plaza, Ltd. Health Affairs SPH, Epidemiology Research Program Overhead Receipts 136 E. Rosemary St Mth to Mth 11,987 $ 243,967.23 $ 20.35 None 4 Yaggy Corporation Health Affairs SPH/SOM Horizons Program University Support Trust Funds 400 Roberson Street Mth to Mth 17,864 $ 323,887.52 $ 18.13 None 5 Chapel Hill Foundation Real Estate Health Affairs Carolina Population Center Research Program Overhead Receipts 143 West Franklin St Mth to Mth 25,952 $ 518,780.48 $ 19.99 None 6 Franklin Street Plaza, LLC University Administration UNC-CH Research Compliance Program University Support Overhead Receipts 137 East Franklin Street Mth to Mth 640 $ 13,572.73 $ 21.21 None 7 Franklin Street Plaza, Ltd. Health Affairs UNC-CH Research Compliance Program Research Program Overhead Receipts 136 E Rosemary St Mth to Mth 196 $ 4,012.12 $ 20.47 None 8 Ambient Air, LLC Health Affairs SPH, Maternal & Child Health/ Epidemiology Research Program Contracts & Grants 116 S Merritt Mill Rd Mth to Mth 2,400 $ 43,800.00 $ 18.25 None 9 Madison Partners, LLC Health Affairs Carolina Population Center Research Program Overhead Receipts 211-B West Cameron St. Mth to Mth 5,730 $ 102,612.82 $ 17.91 None 10 Breadmans Health Affairs Institute for the Environment University Support Capital Improvement337 W Rosemary Mth to Mth 2,639 $ 47,497.50 $ 18.00 None 11 Carr Mill Mall Limited Partnership Health Affairs Morehead Planetarium & Science Ctr University Support Overhead Receipts 200 N. Greensboro St. 3/31/2012 627 $ 10,822.02 $ 17.26 One 1 yr no inc 12 Madison Partners, LLC Health Affairs Graduate Student Center University Support Overhead Receipts 211-A West Cameron Ave. 3/31/2012 2,797 $ 50,741.52 $ 18.14 One 1yr w/ 3% inc 13 Franklin Street Plaza, LLC Academic Affairs OVCRED University Support Overhead Receipts 136 E Rosemary St 4/30/2012 1,073 $ 22,535.14 $ 21.00 OneNone 6 mth w/ 3% 14 Franklin Street Plaza, LLC Citizens Soldier Support Program Overhead Receipts 136 E. Rosemary St 6/30/2012 996 $ 21,115.20 $ 21.20 inc 15 Cedar Plank, LLC Health Affairs SOM, UNC TEACCH Clinical Program Trust Funds 100 Renee Lynn Ctr. 6/30/2012 1,282 $ 22,576.02 $ 17.61 None 16 Cedar Plank, LLC Health Affairs SOM, UNC Autism Center Clinical Program Trust Funds 100 Renee Lynn Court 6/30/2012 12,697 $ 223,594.17 $ 17.61 None 17 * Carr Mill Mall Limited Partnership Health Affairs Lineberger Cancer Ctr Research Program Trust Funds 200 N. Greensboro St. 6/30/2012 1,355 $ 23,373.75 $ 17.25 One 1 year no inc 18 * Chapel Hill Foundation Real Estate Health Affairs Unified Business Center University Support Overhead Receipts 143 West Franklin St 6/30/2012 942 $ 7,300.50 $ 15.50 One 6 mth no inc 19 * Chapel Hill Foundation Real Estate Health Affairs SOM, Infectious Diseases Research Program Contracts & Grants 143 West Franklin St 6/30/2012 228 $ 2,109.00 $ 18.50 None 20 Madison Partners, LLC University Administration Center for Public Service University Support Overhead Receipts 205 Wilson Street 7/31/2012 1,955 $ 40,062.06 $ 20.49 Two 1-yr w/ 3% inc 21 Bell Family Properties, LLC Health Affairs World View Research Program Trust Fund 208 N. Columbia St. 7/31/2012 1,473 $ 24,999.00 $ 16.97 None 22 Riddle Commercial Properties, Inc. Academic Affairs Center for Developmental Science Research Program Overhead Receipts 100 E Franklin St 9/30/2012 11,003 $ 260,063.00 $ 23.64 None 23 Franklin Street Plaza, Ltd. University Administration Office of Research Information Systems Public Service Overhead Receipts 136 E Rosemary St 11/30/2012 3,150 $ 66,181.50 $ 21.01 None 24 Franklin Street Plaza, Ltd. Health Affairs SPH, Injury Prevention Research Center Research Program Overhead Receipts 136 E Rosemary St 12/31/2012 6,555 $ 145,324.35 $ 22.17 None 25 * Franklin Street Plaza, Ltd. Health Affairs SPH, Collaborative Studies Coordinating Ctr Research Program Overhead Receipts 136 E Rosemary St 1/31/2013 332 $ 7,149.74 $ 21.01 None 26 * Franklin Street Plaza, Ltd. Health Affairs SPH, Collaborative Studies Coordinating Ctr Research Program Overhead Receipts 136 E Rosemary St 1/31/2013 16,444 $ 354,167.78 $ 21.54 None Overhead Receipts/ 27 Carr Mill Mall Limited Partnership 101 E. Weaver Street 2/28/2013 10,185 $ 186,432.00 $ 18.30 Two 1-yr w/ 2% inc Academic Affairs School of Law (5,373 sq ft) University Support Trust Fund Health Affairs Scales (2,536 sq ft) Research Program Health Affairs Dr Lea (126 sq ft) Research Program Health Affairs Child Medical (2,150 sq ft) Research Program 28 Europa Ctr LLC Health Affairs RENCI Research Program Overhead Receipts 100 Europa Drive 3/31/2013 3,743 $ 85,517.66 $ 22.85 None 29 Franklin Street Plaza, Ltd. Health Affairs SOM, Health Behavior and Health Education Research Program Trust Funds 136 E Rosemary St 4/30/2013 4,700 $ 93,914.50 $ 19.98 None 30 Board of Trustees of Endowment FundSee Page 5 See Page 5 See Page 5 See Page 5 720, 725, 730 MLK Blvd 6/30/2013 63,471 $ 1,237,684.50 $ 19.50 Two 1yr w/ 3% inc 31 Franklin Street Plaza, Ltd. Health Affairs Institute for the Environment Academic Program Trust Funds 136 E Rosemary St 7/31/2013 4,919 $ 98,891.85 $ 20.10 None 32 Franklin Street Plaza, Ltd. Health Affairs Institute for the Environment University Support Various 136 E Rosemary St 7/31/2013 4,166 $ 83,736.60 $ 20.10 None 33 * Carr Mill Mall Limited Partnership Health Affairs Medical Allied Health Clinical Program Overhead Receipts 200 N. Greensboro St. 8/31/2013 1,803 $ 31,101.75 $ 17.25 None 34 James L. Hodgin Health Affairs FPG Child Development Institute Research Program Overhead Receipts 517 S. Greensboro St 8/31/2013 17,500 $ 351,400.00 $ 20.08 None 35 Sheryl-Mar, LLC Health Affairs FPG Child Development Institute Research Program Overhead Receipts 517 S. Greensboro St 8/31/2013 6,918 $ 133,665.60 $ 19.32 None 36 Sheryl-Mar Company, LLC Health Affairs FPG Child Development Institute Research Program Overhead Receipts 521 S. Greensboro St 12/31/2013 23,532 $ 484,759.20 $ 20.60 None 37 Phillip D. Pearsall Health Affairs SPH, Department of Nutrition Research Program Overhead Receipts 800 Eastowne Drive 12/31/2013 3,186 $ 42,660.54 $ 13.39 Three 1 yr w/3% inc 38 Carr Mill Mall Limited Partnership Health Affairs Medical Allied Health Clinical Program Contracts & Grants 200 N. Greensboro St. 1/31/2014 637 $ 10,192.00 $ 16.00 None 39 Carr Mill Mall Limited Partnership University Administration Advising for/Undergraduate Admissions Academic Program Trust Funds 200 N. Greensboro St. 5/31/2014 1,144 $ 19,448.00 $ 17.00 None 40 First State Investors Ackland Museum Store/ Equal Opportunity-ADAUniversity Support Overhead Receipts 100 E. Franklin Street 5/30/2015 5,788 $ 123,052.88 $ 21.26 None 40 Chapel Hill Foundation Real Estate Health Affairs Carolina Population Center Gates Foundation Research Program Overhead Receipts 143 West Franklin St 6/30/2015 1,841 $ 35,782.71 $ 19.44 One 3yr w/3% inc 41 * Carr Mill Mall Limited Partnership University Administration University Advancement University Support Overhead Receipts 200 N. Greensboro St. 5/16/2016 1,812 $ 31,257.00 $ 17.25 None 296,140 $ 5,820,441.54 $ 19.14 1. Leases executed or renewed since last report (7/11) are denoted by an asterisk (*). During this time, the amount of office space leased in Chapel Hill/Carrboro decreased by 3,409 sq ft. The average cost per square foot increased from $19.61 per square foot to $19.20 per square foot. 2. Amounts shown for Annual Rent and $ Per Square Foot are based on amounts currently being paid. Most leases include provisions for annual rent increases based on a fixed schedule or increases in building operating costs. 3. For lease #1 , #2, #3, #4 COS has approved and waiting on leases from AG's Office 4. For leases #6, #7, #8, #9 are in lease process. 4. Utilities and Janitorial are paid for by the Lessor for all leases shown except for lease #8, #9, #12, #28, #34 5. Janitorial services are provided at the Lessor's cost for all leases shown except #20, #22, #40 6. Utilities are paid for by the Lessor for all leases shown except for lease #4, #15, #16, #35, #36 7. Lease #11 is for a 6 month term (not annual rent) 8. Lease #19 is for a 6 month term (not annual rent) Page 3 The University of North Carolina at Chapel Hill Office Space Leased to UNC-CH Outside of Chapel Hill/Carrboro As of January 1, 2012 Lessee Source of Lease End Building Sq Renewal Owner/Lessor Lessee Division Department Lessee Classification Funding Location Date Ft Annual Rent $ Per Sq ft Options 1 FRIC Haywood Park, LLC Health Affairs SOM, Asheville TEACCH Program Clinical Program State Funds Asheville Mth to Mth 3,795 $21,868.70 $13.83 None 2 Self-Help Ventures Fund Health Affairs SOM, Greensboro TEACCH Program Clinical Program State Funds Greensboro Mth to Mth 2,905 $51,128.00 $17.60 None 3 Commercial Investors C/O James Little Real Estate Health Affairs SOM, Thurston Arthritis Center Clinical Program Contracts & Grants Smithfield Mth to Mth 2,776 $30,528.00 $11.00 None 4 Wainwright Property Mgmt LLC Health Affairs SOM, Greenville TEACCH Program Clinical Program State Funds Greenville Mth to Mth 2,800 $31,799.04 $11.36 None 5 Highwoods Realty Limited Partnership Health Affairs Dental School Research Program State Funds Durham 2/28/2012 62,899 $1,260,614.00 $20.04 None School of Journalism/Mass 6 * Edgemont Tenant LLC Academic Affairs Communication Academic Program State Funds Durham 6/30/2012 167 $1.00 $0.00 None 7 Highwoods Realty Limited Partnership Health Affairs Useful Speech Project Clinical Program Contracts & Grants Durham 7/31/2012 1,293 $16,958.52 $13.12 None 8 Abinto Corporation Health Affairs SOM, Wilmington TEACCH Program Clinical Program State Funds Wilmington 8/31/2012 689 $10,755.29 $15.61 None Contracts & Grants/ two-1yr 9 Fortune's Ridge Associates Limited Partnership Health Affairs SOM. CCDP/CASTLE Clinical Program Trust Durham 12/31/2012 5,149 $96,234.81 $18.69 w/2% inc three-5yr 10 Abinto Corporation Health Affairs SOM, Wilmington TEACCH Program Clinical Program State Funds Wilmington 1/31/2013 3,353 $52,356.81 $15.61 w/2.5%inc Contracts & Grants/ 11 Beacon Ventures Health Affairs Hunt Institute Research Program Trust Durham 3/31/2013 4,527 $112,314.87 $24.81 One 5 yr 12 Keystone 100, LLC Health Affairs Institute of Medicine/Sheps Research Program Trust Fund/COH Durham 4/30/2013 4,328 $103,944.17 $24.02 None Contracts & Grants/ 13 Fortune's Ridge Associates Limited Partnership Health Affairs SOM. CCDP/CASTLE Clinical Program Trust Durham 2/28/2014 1,180 $20,650.00 $17.50 None 14 Seamist Properties Fayetteville LLC Health Affairs SOM, Fayetteville TEACCH Program Clinical Program State Funds Fayetteville 2/28/2014 3,100 $49,135.00 $15.85 None 15 * The Kinston Enterprise Center Health Affairs HPDP-Healthy Heart Lenoir Project Research Program Contract & Grants Kinston 7/31/2014 824 $8,568.00 $10.40 None 16 East Park Associates, LLC Health Affairs SOM, Charlotte TEACCH Program Clinical Program State Funds Charlotte 4/30/2015 2,990 $48,150.49 $16.10 None 102,775 $1,915,006.70 $15.35 NOTES: 1. Leases executed or renewed since the last report (7/11) are denoted with an asterisk (*). Sq ft outside Chapel Hill/Carrboro represented no change in leased square feet since last lease report in January, 2011 sq ft). 2. Amounts shown for Annual Rent and $ Per Square Foot are based on amounts currently being paid. Most leases include a provision for annual rent increases based on a fixed schedule or increases in building operating costs. 3. Utilities and janitorial services are provided by the Lessor for all leases except #5, #8, #14, 4. Janitorial services not included in #9, #10, #13, #15 5. Lease #1 COS approved. Waiting on new lease from AG's office 6. Lease #6 $1.00 for six month lease term Page 4 The University of North Carolina at Chapel Hill Endowment Owned Buildings on MLK Jr. Blvd. Office Space Leased to UNC-CH As of January 1, 2012 $ Per Square Lessor Lessee Division Lessee Department (Program) Lessee Classification Lessee Source of Funds Square Feet Annual Rent Foot Endowment Fund Health Affairs School of Medicine (Dr. Drossman) Research Program Overhead Receipts 579 $11,290.50 $19.50 Endowment Fund Health Affairs School of Medicine (Division of Cardiology Heart Failure Prog.) Research Program Contracts & Grants 311 $6,064.50 $19.50 Overhead Receipts Trust Endowment Fund Health Affairs School of Public Health (Institute on Aging) Research Program 8,771 $171,034.50 $19.50 Funds Endowment Fund Health Affairs School of Public Health (Biostatistics Dept, Survey Res. Unit) Research Program Overhead Receipts 5,811 $113,314.50 $19.50 Endowment Fund Health Affairs Cecil G. Sheps Center For Health Services Research Research Program Overhead Receipts 34,777 $678,151.50 $19.50 Overhead Receipts Trust Endowment Fund Health Affairs Highway Safety Research Center Research Program 13,222 $257,829.00 $19.50 Funds Total 720, 725, 730 Martin Luther King Jr. Blvd 63,471 $1,237,684.50 $19.50 Page 5 The University of North Carolina at Chapel Hill Miscellaneous Leases to the University As of January 1, 2012 Owner/Lessor Lessee Division Department Type Location Lease End Date Sq Ft or Acres Annual Rent 1 Carolina Telephone and Telegraph Company University Admin WUNC Radio Tower & Roof Top Dare County (See Note 1) mth-to-mth 0 $0.00 2 Secretary of the Army University Admin University of North Carolina Land Kerr Lake (see Note 2) mth-to-mth 230 acres $0.00 3 * Chapel Hill Group Limited Partnership Health Affairs SOM, Dermatology Apartment Carrboro (See Note 3) 5/31/2012 759 sq ft $3,510.00 4 Loretta Malcolm Health Affairs SPH, Environmental Sciences & Engineering Land Chatham 6/30/2012 2 acres $3,025.00 5 GTP Acquisition Partner II, LLC University Admin WUNC Radio Tower & Roof Top Edgecombe County (See Note 1) 12/31/2017 100 sq ft $17,557.94 Frank Porter Graham Child Development 6 Chapel Hill City Board of Education Health Affairs Institute Land Chapel Hill 9/17/2019 10.81 acres $0.00 7 RDU International Health Affairs AHEC Facility Land RDU -Durham 12/1/2030 70,390 $8,448.00 $32,540.94 * Leases executed or renewed since the last report (7/11) are denoted with an asterisk (*). 1. Tower, rooftop and associated land space to locate FM broadcast antenna and transmitter. Item #1 Working with State Property Office to secure new lease. 2. Use of space for picnics, boating, camping, swimming and nature studies or current and retired University employees, University Hospital employees and General Administration employees. Working with Secretary of the Army and the State Property Office to secure a new lease. 3. Rental cost reflects 6 mth term U/J services are not included for Dermatology Lease. Page 6 The University of North Carolina at Chapel Hill Lease Summary Storage Space Leases As of January 1, 2012 Owner/Lessor Department Storage Type Lease End Date Building Sq Ft Annual Rent 1 Starpoint, Inc. Highway Safety Research Center Mini 4/30/2012 200 $ 1,680.00 2 Yarboro & Hessee Warehouses, LLC Ackland Art Bulk 7/31/2012 1,888 $ 8,496.00 3 * Charlotte EAST, LLC Charlotte TEACCH Center Mini 9/30/2012 472 $ 3,776.00 Notes: 2,560 $ 13,952.00 * Leases executed or renewed since the last report (7/11) are denoted with an asterisk (*). Page 7 The University of North Carolina at Chapel Hill Summary of Lease Dispositions As of January 1, 2012 Location Lessee's Name Sq ft Monthly Rent Annual Rent Lease End Date I. Rental Houses 1 1506B Mason Farm Road, Chapel Hill Andrew Pukal 900 $550.00 $6,600.00 Mth to Mth 2 2311 Homestead Road, Chapel Hill Michael & Denise Lopez 2,306 $1,450.00 $17,400.00 Mth to Mth 3 12276 US Highway 15-501 North, Pittsboro VACANT 1,300 4 1303 Mason Farm Road, Chapel Hill Lyneise Williams 2,314 $1,500.00 $18,000.00 Mth to Mth 5 109 Chase Ave, Chapel Hill VACANT 2,324 6 301 Chase Avenue, Chapel Hill Stephen Seiberling 1,940 $1,200.00 $14,400.00 5/31/2012 7 6627 Maynard Farm Road VACANT 1,846 8 218 Wilson Street, Chapel Hill Steven Dobbins 1,500 $1,275.00 $15,300.00 7/30/2012 9 University Lake (Lake Warden's House) Orange Water and Sewer Authority 1,080 $0.00 $1.00 2/14/2012 10 1307 Mason Farm Road, Chapel Hill Eric McAfee 3,010 $1,450.00 $17,400.00 2/28/2012 11 1404 Mason Farm Road, Chapel Hill VACANT 1,775 12 1309 Homestead Road, Chapel Hill Robert & Nadine Woods 1,649 $1,125.00 $13,500.00 4/30/2012 13 611 East Franklin Street (Horace Williams House) The Chapel Hill Preservation Society 2,600 $0.00 $1.00 6/30/2012 14 114B Chase Avenue, Chapel Hill Emily Given 780 $550.00 $6,600.00 6/30/2012 114A Chase Avenue, Chapel Hill Skyler Wason & Dana Falkenberg 1,100 $1,000.00 $12,000.00 7/31/2012 15 107 Chase Avenue, Chapel Hill Bryan Richardson 2,324 $1,400.00 $16,800.00 7/31/2012 16 620 Park Place, Chapel Hill Ronald A. Difelice 1,400 $1,375.00 $16,200.00 8/31/2012 17 1450 Mason Farm Place, Chapel Hill David and Susan Demers 3,196 $1,400.00 $16,800.00 1/31/2013 18 1500 Mason Farm Road, Chapel Hill Jeremy & Guenieve Moulton 2,429 $1,375.00 $16,500.00 5/31/2013 19 307 W Cameron Ave, Chapel Hill Deborah Miller 2,936 $2,050.00 $24,600.00 5/31/2013 20 1402 Mason Farm Road, Chapel Hill Tim Carless 3,200 $1,150.00 $13,800.00 6/30/2013 21 1301 Mason Farm Road, Chapel Hill Robert Marciano & Anna Lopez 2,609 $1,400.00 $16,800.00 6/30/2013 44,518 $20,250.00 $242,702.00 Location Lessee's Name Monthly Rent Annual Rent Lease End Date II. Rental Buildings 1 Carolina Inn, Chapel Hill NC BOT of the Endowment Fund 118,780 $0.00 $1.00 6/30/2041 2 Mason Farm Road Environmental Protection Agency 66,000 $450,810.00 $5,409,720.00 1/31/2015 184,780 $ 450,810.00 $5,409,721.00 Notes Page 8 The University of North Carolina at Chapel Hill Summary of Lease Dispositions As of January 1, 2012 Location Lessee's Name Land Acreage Annual Rent Lease End Date III. Land Leases 1 Chapel Hill-Carrboro Bikeway Town of Carrboro 0.70 $1.00 mth-mth 3 UNC-CH campus at Stadium Drive-Kenan Stadium The Educational Foundation, Inc. 3.33 $0.00 12/31/2012 4 University Lake Orange Water and Sewer Authority 9.30 $0.00 8/8/2016 5 Park & Ride Lot near University Lake, Carrboro Town of Chapel Hill 7.00 $1.00 5/19/2019 6 Old Mason Farm Road Family House at UNC Hospitals 5.83 $1.00 5/31/2031 7 Smith Middle School Playing Fields Orange Co., NC 16.60 $0.00 7/13/2031 8 UNC-CH campus -George Watts Hill Alumni Center General Alumni Association 4.10 $1.00 10/1/2034 9 101 Old Mason Farm Road Ronald McDonald House of Chapel Hill 2.04 $1.00 10/31/2035 10 208 Finley Golf Course Rd Beta XI Chapter, Kappa Psi Pharmaceutical Frat. 1.38 $0.00 8/5/2068 11 Barbee Chapel Rd UNC Faculty Staff Recreation Association, Inc. 28.00 $0.00 7/7/2075 12 222 Finley Golf Course Rd. North Carolina High School Athletic Association 1.45 $1.00 5/13/2088 13 1411 Homestead Road, Chapel Hill Town of Carrboro 1.68 $1.00 11/30/2105 81.41 $7.00 Location Lessee's Name Land Acreage Annual Rent Lease End Date IV. Miscellaneous Leases Horace Williams Airport (South of Runway 27) US Dept. of Trans., Federal Aviation Admin. N/A $0.00 9/30/2015 Notes Page 9 Attachment C Preliminary Design Craige Deck Expansion Little Diversified Architectural Consulting January 26, 2012 Craige Deck Expansion Context Plan January 2012 Craige Deck Expansion Site Plan January 2012 Craige Deck Expansion Manning Dr. Perspective Proposed North Elevation January 2012 UNC-Chapel Hill Board of Trustees Special Full Board Minutes December 9, 2011 OPEN SESSION APPOINTMENT AND CONTRACT OF FOOTBALL COACH, LARRY FEDORA Athletic Director Cunningham presented the terms of the contract for the head football coach and answered questions. Trustee Shuping-Russell moved to approve the appointment of Larry Fedora as Head Football Coach, upon the terms and conditions set forth in the employment agreement in Attachment A. The motion was duly seconded and passed unanimously. (ATTACHMENT A) Chancellor Thorp commented on the search process, expressing appreciation to Athletic Director Cunningham for the team approach involving his assistants, thorough homework, integrity and overall professionalism of the entire search process resulting in and securing an outstanding head football coach for Carolina. Chair Hargrove echoed the chancellor’s comments and congratulated Mr. Cunningham on behalf of the entire board. ADJOURNMENT There being no further business to come before the Board, Chair Hargrove adjourned the meeting at 9:33 a.m. 2 COUNTY OF ORANGE STATE OF NORTH CAROLINA EMPLOYMENT AGREEMENT HEAD FOOTBALL COACH THIS EMPLOYMENT AGREEMENT (this “Agreement”), made and entered into as of the 9th day of December, 2011, is by and between The University of North Carolina at Chapel Hill (“University”) and Larry Fedora (“Coach”). W I T N E S S E T H: WHEREAS, University desires to employ Coach as Head Football Coach and Coach desires to engage in such employment under the terms and conditions set forth below; and WHEREAS, the parties acknowledge that, although this Agreement is sports-related, the primary mission of the University is education, and, accordingly, the primary purpose of all of the University’s legal arrangements, including this Agreement, is the furtherance of the University’s educational mission; NOW, THEREFORE, in consideration of the premises and the mutual covenants hereinafter set forth, it is agreed as follows: I. TERM OF EMPLOYMENT University agrees to employ Coach and Coach agrees to serve as the University’s Head Football Coach for a term beginning December 29, 2011, and continuing until January 15, 2019. Although this Agreement may be executed on a date other than December 29, 2011, the parties shall treat the effective date of this Agreement as December 29, 2011. {00050633.DOC 6} II. DUTIES Coach is hereby employed by University as Head Football Coach with all of the duties, responsibilities, obligations, and privileges as are assigned to him by the Athletic Director, which duties may include, without limitation, the following: (a) directing and conducting the Football Program in keeping with the educational purpose of and the traditions, values, integrity, and ethics of the University; (b) recruiting and retaining only academically qualified student-athletes and promoting and encouraging academic progress, in conjunction with the faculty and University, of such student-athletes toward graduation in defined degree programs; (c) conducting himself and the Football Program in accordance with all applicable rules, regulations, and policies of and applicable to University and in accordance with the Constitution, bylaws, legislation, and regulations of the Atlantic Coast Conference (“ACC”) and of the National Collegiate Athletic Association (“NCAA”), as such may be amended from time to time. Coach shall promptly advise the Athletic Director if Coach has reason to believe that violations have occurred or will occur and shall cooperate fully in any investigation of possible violations conducted or authorized by the University, the ACC, or the NCAA at any time; (d) supervising and maintaining responsibility for the conduct and activities of all assistant football coaches, football program staff members, employees, and student-athletes under Coach’s supervision, including maintaining good faith compliance by all such individuals with all applicable rules, regulations and policies of and applicable to University and with the Constitution, bylaws, legislation, and regulations of the ACC and NCAA, as such may be amended from time to time. This responsibility shall include, without limitation, developing reasonable processes for monitoring football program compliance and providing annual evaluations of such assistant coaches and staff members; (e) under the direction of the Athletic Director, maintaining responsibility for the fiscal and budgetary functions associated with the Football Program; (f) cultivating and maintaining effective relations with students, faculty, staff, and friends of the University; and (g) such other reasonable duties as may be assigned by the Athletic Director from time to time, consistent with those duties typically applicable to a Division I head football coach. Coach agrees faithfully and diligently to use his best efforts to perform all the duties of the position of Head Football Coach and to devote such time, attention, and skill to the {00050633.DOC 6}- 2 - performance of these duties as necessary. During the term of this Agreement, Coach shall report to and be under the immediate supervision of University’s Athletic Director and shall regularly confer with the Athletic Director on matters concerning administrative and technical decisions. Without limiting the generality of the foregoing, Coach shall have the responsibility and authority, in consultation with the Athletic Director and consistent with all applicable University policies, as such may be amended from time to time, to employ and discharge all personnel assigned to the Football Program. III. COMPENSATION (a) The annual salary of Coach for the position of Head Football Coach shall be Three Hundred Fifty Thousand Dollars ($350,000). This is based on a twelve-month employment period commencing on January 16 and concluding on January 15 of the succeeding year (such period being referred to herein as a “contract year”) and shall be pro-rated for any partial contract year. (b) In any year in which the Football team wins its division within the Atlantic Coast Conference (“ACC”), Coach will receive additional compensation from University in the form of a bonus for increased responsibilities in an amount equal to one-twelfth (1/12) of his then- applicable annual salary, as determined pursuant to Section III(a). Any amount earned hereunder shall be paid within seventy-five (75) days following the ACC Conference Championship game. (c) In any year in which the Football team wins the ACC Conference Championship, Coach will receive additional compensation from University in the form of a bonus in an amount equal to one-twelfth (1/12) of his then-applicable annual salary, as determined pursuant to Section III(a). Any amount earned hereunder shall be paid within seventy-five (75) days following the ACC Conference Championship game. (d) In any year in which the Football team is invited to participate in a post-season bowl game other than a BCS game, Coach will receive, in addition to any compensation due pursuant to Sections III (a), (b), and (c) above, additional compensation from University in the form of a bonus for increased responsibilities in an amount equal to one-twelfth (1/12) of his then-applicable annual salary, as determined pursuant to Section III(a). In any year in which the Football team is invited to participate in a post-season BCS bowl game, Coach will receive, in addition to any compensation due pursuant to Sections III (a), (b), and (c) above, additional compensation from University in the form of a bonus for increased responsibilities in an amount equal to two-twelfths (2/12) of his then-applicable annual salary, as determined pursuant to Section III(a). Any amount earned hereunder shall be paid within seventy-five (75) days following the bowl game. (e) In any year in which the Football team participates in the BCS National Championship game, Coach will receive additional compensation from University in the form of a bonus in an amount equal to Two Hundred Thousand Dollars ($200,000). Any amount earned hereunder shall be paid within seventy-five (75) days following the ACC Conference Championship game. {00050633.DOC 6}- 3 - (f) In any year in which the four year “Academic Progress Rate” for the Football team reported by the University to the NCAA equals or exceeds 960, Coach will receive, in addition to the compensation specified in subparagraphs III (a) - (e) above, additional compensation from University in the form of a bonus in an amount equal to one-twelfth (1/12) of his then-applicable annual salary, as determined pursuant to subparagraph III(a). For purposes hereof, the term “Academic Progress Rate” shall be as defined by the NCAA. Any amount earned hereunder shall be paid within seventy-five (75) days after the University submits its annual Academic Progress Rate report to the NCAA. IV. BENEFITS The position of Head Football Coach is classified as an EPA Non-Faculty Employee of the University. As an EPA Non-Faculty Employee, Coach shall be entitled to receive all employee-related benefits which are normally available to other twelve-month EPA Non-Faculty Employees. Coach’s employment is subject to the Employment Policies for EPA Non-Faculty Research Staff, Instructional Staff, and Tier II Senior Academic and Administrative Officers of The University of North Carolina at Chapel Hill, as adopted by the Board of Trustees and as revised from time to time (the “Policies”). A copy of the current Policies is attached hereto and incorporated herein by reference. Coach acknowledges that benefits or classifications provided by University are subject to change from time to time by the North Carolina Legislature or the University. In addition to the benefits generally accorded an EPA Non-Faculty Employee, so long as Coach continues to serve as University’s Head Football Coach, University shall provide to Coach the following additional benefits: (a) Coach or an entity controlled by Coach shall be entitled to operate a summer football camp in accordance with the policies of University concerning the operation of such camps, as discussed in more detail in Section VI below. (b) Coach shall be entitled to advise and comment on all proposed scheduling of University football games during the term of this Agreement. V. EXPENSES While Coach holds the position of Head Football Coach, Coach will receive an annual expense allowance from the Department of Athletics of Thirty Thousand Dollars ($30,000) per year to be used for entertainment and other appropriate purposes to advance University’s Football Program. All appropriate State and Federal taxes will be withheld from this allowance. This allowance may be adjusted for inflationary and other reasons during the term of this Agreement. This will be at the discretion of the Athletic Director, but will at no time be reduced below the amount set forth above per contract year. Use of these funds shall always be consistent with NCAA, ACC, and University regulations, but Coach shall not be required to report specific expenditures to the University. {00050633.DOC 6}- 4 - VI. OUTSIDE COMPENSATION (a) Subject to compliance with the Policy on External Professional Activities for Pay of The University of North Carolina Board of Governors, NCAA and ACC Regulations, and subject to all other relevant policies applicable to or of the University and laws concerning conflicts of interest, and with the prior approval from the Athletic Director and Chancellor as provided in said policies, Coach may earn other revenue while employed by University, but such activities are independent of his University employment, and the University shall have no responsibility for any claims by Coach or against Coach arising therefrom. Activities permitted under this Section VI shall include engaging in any radio, television, motion picture, writing, or any similar activity, personal appearances, commercial endorsements, and summer football camps, except as noted below. With respect to any such independent activities that are commercial in nature, including, without limitation, activities that promote a private business or service, Coach shall not, without the express written permission of University, make use of University’s name, logos, or symbols. (b) With respect to the operation of summer football camps or other activities using University’s name, such activity shall be only with the prior approval of the Athletic Director and Chancellor, which approval shall not be unreasonably withheld, and shall be conducted in accordance with all applicable NCAA and ACC policies and policies of or applicable to University, including those requiring the payment of fees for use, if any, of University facilities. (c) As required by NCAA Regulations, Coach shall report annually as of July 1 to the Chancellor through the Athletic Director all athletically related income from sources outside the University, including but not limited to, income from annuities, sports camps, endorsements, television and radio programs, and all other athletically-related income from whatever outside source. University shall have reasonable access to all records of Coach to verify this report. VII. UNIVERSITY RECORDS All materials or articles of information including, without limitation, personnel records, recruiting records, team information, films, statistics, or any other material or data furnished to Coach by University or developed by Coach on behalf of University or at University’s direction or for University’s use or otherwise in connection with Coach’s employment hereunder are and shall remain the sole property of University. If University requests the return of such materials at any time during, or at, or after the termination of Coach’s employment, Coach shall immediately deliver same to University. Coach acknowledges that this Agreement is a public record subject to disclosure under North Carolina’s Public Records Law. {00050633.DOC 6}- 5 - VIII. PROGRAM SUPPORT In addition to the duties outlined in Section II of this Agreement: (a) Coach agrees to attend a specified number of Educational Foundation Chapter meetings per year to promote University’s Football Program, the number to be reasonably determined on an annual basis by the Athletic Director. (b) Coach agrees to maintain and cultivate effective relations with students, faculty, staff and friends of the University. (c) Coach agrees that University shall have the right to use the name, likeness and image of Coach in promoting and developing the Football Program, provided that any such use shall not be in poor taste or reflect negatively upon Coach. IX. TERMINATION BY UNIVERSITY FOR CAUSE This Agreement may be terminated by University for Cause at any time upon written notice to Coach. For purposes hereof, “Cause” shall mean the following: (a) material failure to perform any of the duties specified in Section II of this Agreement; (b) a violation of a major ACC or NCAA regulation or bylaw, as reasonably determined in the sole discretion of University after its review of the relevant facts and circumstances: (i) by Coach; or (ii) in which Coach knowingly participated. (c) a violation of a major ACC or NCAA regulation or bylaw, as reasonably determined in the sole discretion of University after its review of the relevant facts and circumstances by any assistant football coach, football program staff member, employee, or student-athlete under Coach’s supervision, of which Coach knew, had reason to know, should have known, or which Coach condoned. (d) behavior by Coach that, as reasonably determined in the sole discretion of University after its review of the relevant facts and circumstances, displays a continual or serious disrespect for the integrity, values, and ethics of the University or its Football Program or which has or is likely to have a material adverse impact on the reputation or good name of the University or its Football Program; (e) any other material breach by Coach of the terms of this Agreement; or (f) any of those causes specified in Section VIII of the University’s Employment Policies for EPA Non-Faculty Research Staff, Instructional Staff, and Tier II Senior Academic and Administrative Officers of the University, as such Employment Policies may be amended from time to time. {00050633.DOC 6}- 6 - In the event of a termination under this Section IX for “Cause,” University’s sole obligation to Coach shall be payment of his compensation as set forth in Section III of this Agreement earned through the date of such termination. The University shall not be liable to Coach for any collateral business opportunities, outside activities, or other non- University matters that may be related to or associated with Coach’s position as Head Football Coach. Any process to terminate Coach for Cause shall be conducted in compliance with all relevant University policies. X. AUTOMATIC TERMINATION UPON DEATH OR DISABILITY OF COACH (a) This Agreement shall terminate immediately and automatically without notice in the event that Coach dies. This Agreement shall terminate, upon reasonable notice to Coach by University, in the event that Coach becomes and remains unable to perform the essential functions of his employment hereunder for a period of ninety (90) consecutive days or ninety (90) days in any one hundred fifty (150) day period by reason of medical illness or incapacity. Such determination of Coach’s inability to perform his duties shall be made in the sole judgment of the Chancellor and Athletic Director; provided, however, that the Chancellor and Athletic Director shall, prior to making such judgment, seek the advice and opinion regarding such disability of an impartial physician competent to provide such advice and opinion, as may be mutually agreed upon by Coach or his legal representative(s) and the Athletic Director of University. If Coach or his legal representative(s), as the case may be, and the Athletic Director are unable to agree upon such physician, the selection shall be made by the Dean of the School of Medicine of The University of North Carolina at Chapel Hill. (b) If this Agreement is terminated pursuant to Section X(a) above because of death, the Coach’s salary and all other benefits shall terminate as of the end of the calendar month in which death occurs, except that the Coach’s personal representative(s) or other designated beneficiary shall be paid all death benefits, if any, as may be contained in any benefit plan now in force or hereafter adopted by the University and due the Coach as an EPA Non-Faculty Employee under the University Policies. (c) In the event that Coach becomes and remains unable, in the sole judgment of the Chancellor and Athletic Director, to perform the essential functions of his employment hereunder for a period of ninety (90) consecutive days or ninety (90) days in any one hundred fifty (150) day period because of medical illness or incapacity and the University thereupon affords notice of termination under Section X(a) above, except for (i) payment of amounts due Coach accrued hereunder prior to the date of termination, and (ii) payment of any disability benefits to which Coach may be entitled pursuant to any disability program in which Coach is enrolled through University, the University shall have no further liability to Coach pursuant to this Agreement. Specifically and without limitation, at the end of such ninety (90) or hundred fifty (150) day period, as applicable, all salary and other benefits shall terminate, except that Coach shall be entitled to receive payment of any disability benefits to which he is entitled under any disability program in which he is enrolled through the University. {00050633.DOC 6}- 7 - (d) Notwithstanding any other provision herein, this Agreement does not and shall not be construed to afford University the right to take any action that is unlawful under the Americans with Disabilities Act or to constitute in any respect a waiver of rights under such Act. (e) The termination of this Agreement under Section X(a), above, shall not constitute a breach of this Agreement, and, except for the payments required by this Section X, if any, Coach hereby, to the fullest extent allowable by law, waives and relinquishes all rights to payment of compensation, damages, or other relief on account of such termination. XI. TERMINATION BY UNIVERSITY WITHOUT CAUSE; LIQUIDATED DAMAGES (a) Following consultation with the Athletic Director, this Agreement may be terminated unilaterally by the Chancellor at any time upon written notice to Coach, in the absence of Cause (as “Cause” is defined in Section IX of this Agreement). (b) In the event this Agreement is terminated pursuant to Section XI(a) above, University shall pay Coach liquidated damages in lieu of any and all other legal remedies or equitable relief in an amount equal to the (1) sum of $400,000 plus Coach’s then current annual salary (as determined pursuant to Section III(a) of this Agreement), multiplied by (2) the number of contract years remaining under this Agreement (prorated for any partial year); provided, however, that the liquidated damages payable pursuant to this Section XI(b) shall be subject to offset, as set forth in Section XI(c) below. (c) Payment of the amount determined pursuant to Section XI(b)(1) shall occur over the remaining term of the Agreement as follows: (1) on the effective date of termination without Cause, payment shall be made of amounts due with respect to the remainder of that contract year; and (2) payments due hereunder with respect to each subsequent contract year shall be made on the last day (January 15) of such subsequent contract year, until all amounts due have been paid in full. Coach acknowledges and agrees that the amount of liquidated damages due pursuant to this Section XI shall be reduced by any compensation received by Coach during the time period remaining under this Agreement for services provided by Coach (x) in a coaching position for any college or professional football program or (y) as a commentator for ABC/ESPN, NBC, CBS or their successors or assigns. Coach shall account to University for any such compensation by providing a statement in writing ten (10) business days prior to each scheduled payment date setting forth the amount of such compensation earned by Coach (x) during the preceding contract year, and (y) in total since the effective date of termination. Amounts for services shall be deemed “earned” at the time the services are provided, regardless of when actual payment for such services is received. Except as specifically provided above in this Section XI, the University in such case shall not be liable to Coach for compensation (including supplemental compensation provided for in Section XV), for benefits with respect to periods after the effective date of termination, or for any collateral business opportunities or other benefits or activities entered into pursuant to Section VI of this Agreement which may be related to his position as Head Football Coach. (d) The parties have bargained for and agreed to this liquidated damages provision, giving consideration to the following: (1) this is an Agreement for personal services; and (2) the {00050633.DOC 6}- 8 - parties recognize that a termination of this Agreement by University prior to its natural expiration could cause Coach to lose benefits, compensation, and/or outside compensation relating to his employment at University, which damages are difficult to determine with certainty. Therefore, the parties have agreed upon this liquidated damages provision and further agree that the liquidated damages provided for herein are reasonable in amount and not a penalty. (e) Termination of this Agreement upon the death or disability of Coach, as provided in Section X of this Agreement, shall not give rise to a right to liquidated damages pursuant to this Section XI. XII. TERMINATION BY COACH (a) Coach recognizes that his promise to work for University for the entire term of this Agreement is an essential consideration in University’s decision to employ him as Head Football Coach. Coach also recognizes that the University is making a highly valuable investment in his continued employment by entering into this Agreement and its investment would be lost or diminished were he to resign or otherwise terminate his employment as Head Football Coach with University prior to the expiration of this Agreement. That said, Coach may terminate this Agreement for any reason upon written notice to University. (b) In the event that Coach terminates his employment with the University without cause prior to January 15, 2013, then Coach shall pay University liquidated damages in lieu of any and all other legal remedies or equitable relief in an amount equal to Two Million Three Hundred Fifty Thousand Dollars ($2,350,000). (c) In the event that Coach terminates his employment with the University without cause after on or after January 15, 2013 but prior to January 15, 2014, then Coach shall pay University liquidated damages in lieu of any and all other legal remedies or equitable relief in an amount equal to One Million Dollars ($1,000,000). (d) In the event that Coach terminates his employment with the University without cause on or after January 15, 2014 but prior to January 15, 2015, then Coach shall pay University liquidated damages in lieu of any and all other legal remedies or equitable relief in an amount equal to Five Hundred Thousand Dollars ($500,000). (e) In the event that Coach terminates his employment with the University without cause on or after January 15, 2015 but prior to January 15, 2016, then Coach shall pay University liquidated damages in lieu of any and all other legal remedies or equitable relief in an amount equal to Two Hundred Fifty Thousand Dollars $250,000. (f) In the event that Coach terminates his employment with the University without cause on or after January 15, 2016 but prior to January 15, 2017, then Coach shall pay University liquidated damages in lieu of any and all other legal remedies or equitable relief in an amount equal to One Hundred Thousand Dollars ($100,000). (g) In the event that Coach terminates his employment with the University without cause on or after January 15, 2017 but prior to January 15, 2018, then Coach shall pay University {00050633.DOC 6}- 9 - liquidated damages in lieu of any and all other legal remedies or equitable relief in an amount equal to One Hundred Thousand Dollars ($100,000). (h) Payment of the total amount determined pursuant to Section XII(b), (c), (d), (e), (f) or (g) shall be made by Coach in a lump sum within ninety (90) days after the effective date of Coach’s termination of the Agreement. (i) The parties have bargained for and agreed to the liquidated damages provisions set forth in this Section XII, giving consideration to the following: The parties acknowledge that the University will incur administrative, recruiting, resettlement and other costs in obtaining a replacement Coach in addition to potentially increased compensation costs and loss of ticket, broadcast or other revenues and fan and donor support, which damages are difficult to determine with certainty. Therefore, the parties have agreed upon this liquidated damages provision and further agree that the liquidated damages provided for herein are reasonable in amount and not a penalty. (j) Coach shall have the right to terminate this Agreement for cause without the necessity of his payment of the amounts contemplated in Section XII(b), (c), (d), (e), (f), or (g) above if there is a failure by the University to pay or to provide for the payment on a timely basis of the amounts due under Section III, XIV, or XV of this Agreement, and the University fails to cure such breach within ten (10) business days of the Coach’s providing written notice to the Athletic Director and Chancellor. (k) The parties agree that Coach shall be required to notify the Athletic Director and Chancellor prior to engaging in discussions with other institutions through their representatives or agents, including discussions related to offers of administrative opportunities at other educational institutions. XIII. TERMINATION BY AGREEMENT OF BOTH PARTIES This Agreement may be terminated at any time upon mutual agreement of the parties. XIV. RETENTION BONUS So long as (i) Coach remains employed by University on the applicable January 15, as set forth below, (ii) has not given notice that he intends to terminate this Agreement without cause pursuant to Section XII of this Agreement, and (iii) has performed the essential functions of his job, including recruiting activities, through such date, the University will pay Coach a retention bonus as noted below: January 15, 2015 $100,000 January 15, 2016 $200,000 January 15, 2017 $250,000 January 15, 2018 $300,000 January 15, 2019 $350,000 {00050633.DOC 6}- 10 - XV. SUPPLEMENTAL COMPENSATION In order for University to provide Coach with a compensation package competitive with that provided to head football Coaches at University’s peer institutions, University agrees to make supplemental compensation payments to Coach in the amount of One Million Three Hundred Fifty Thousand Dollars ($1,350,000) per year. The supplemental compensation shall be paid in quarterly installments of Three Hundred Thirty-seven Thousand Five Hundred Dollars ($337,500) which shall be due each March 15, June 15, September 15, and December 15 throughout the term of this Agreement, so long as this Agreement remains in full force and effect on the applicable payment date and notice of termination of this Agreement has not been given. The first payment hereunder shall be due March 15, 2012. XVI. ONE TIME PAYMENT On or before January 31, 2012, the University will make a one-time payment to Coach in an amount that, after the withholding of applicable taxes, will net $400,000 to Coach. XVII. TAXES Coach acknowledges that, in addition to the salary provided for in this Agreement, certain benefits he receives incident to his employment relationship with University may give rise to taxable income. Coach agrees to be responsible for the payment of any taxes (including federal, state, and local taxes) due on such income. Coach also understands that University will withhold taxes on amounts paid or due to Coach and the value of benefits provided to Coach, to the extent required by applicable law and regulation. XVIII. SEVERABILITY The invalidity or unenforceability of any provision hereof shall in no way affect the validity or unenforceability of any other provision hereof. XIX. NOTICES Any notice required or permitted to be given under this Agreement shall be sufficient if in writing, and if sent by registered or certified mail to his residence in the case of Coach, or to the offices of the Director of Athletics and Chancellor, in the case of University. XX. BENEFIT This Agreement, in accordance with its terms and conditions, shall inure to the benefit of and be binding upon University, its successors and assigns, and Coach, his heirs, executors, administrators, and legal representatives. {00050633.DOC 6}- 11 - XXI. SITUS This Agreement shall be construed in accordance with and governed by the laws of the State of North Carolina. The exclusive venue in any judicial action or proceeding arising out of or relating to this Agreement shall be the state or federal courts located in State of North Carolina. XXII. EQUAL PARTICIPANTS Each party hereto shall be viewed as an equal participant, and each party agrees that there shall be no presumption against the drafting party. XXIII. COUNTERPARTS This Agreement may be executed in separate counterparts, each of which when so executed and delivered shall be an original, but all of which shall constitute one and the same instrument. Delivery of executed counterparts of the Agreement by telecopy or electronic signature shall be effective as an original. XXIV. ENTIRE AGREEMENT Effective upon signature by both parties, this instrument cancels all prior agreements between the parties hereto and contains the entire agreement of the parties. It may not be changed orally. This Agreement and any amendments thereto shall be effective only if signed by both parties and approved, as required, pursuant to the policies of the Board of Governors of The University of North Carolina. [Signature Page Follows] {00050633.DOC 6}- 12 - IN WITNESS WHEREOF, the parties hereto have executed this Agreement as of the day and year first above written. FOR AND ON BEHALF OF COACH THE UNIVERSITY OF NORTH CAROLINA AT CHAPEL HILL Lawrence (Bubba) Cunningham Larry Fedora Director of Athletics ______Date Date Holden Thorp Chancellor ______Date Karol Kain Gray Vice Chancellor for Finance and Administration ______Date Approved by the Board of Trustees: Assistant Secretary Date {00050633.DOC 6}- 13 - To: Heather Galvan From: Members of the Board of Trustees Fax: (919) 962-1647 Pages: 1 (including cover sheet) Date: December 6, 2011 Re: Mail Ballot, dated December 5, 2011 Trustees: Attached for your review and approval is a regular personnel mail ballot. This mail ballot will be approved as part of the Consent Agenda at the Full Board meeting on Thursday, January 26, 2012. The undersigned votes as follows with respect to the recommendations proposed in Chancellor Thorp’s letter dated, December 5, 2011. Approve Disapprove Appendix A, Personnel Actions Appendix A, Actions Conferring Tenure Appendix B, Compensation Actions Appendix C, For Information NO ITEMS ______Signed ______Date Please fax to Heather Galvan at (919) 962-1647. The University of North Carolina at Chapel Hill Appendix A EXECUTIVE SUMMARY Board of Trustees December 5, 2011 Effective No. College/Division Name Dept./School Current Rank New Rank Date Salary Personnel Actions New Appointments without Tenure 1 Academic Affairs Erika Wilson Law N/A Assistant Professor 1/1/2012 $110,500 2 Academic Affairs Zeina Halabi Asian Studies N/A Assistant Professor 1/1/2012 $65,000 Promotion to Full Professor 1 Health Affairs Janet Guthmiller Periodontology Associate Professor Professor 1/1/2012 $156,969 2 Health Affairs George Retsch-Bogart Pediatrics Associate Professor Professor 2/1/2012 $179,192 3 Health Affairs Andre Ritter Operative Dentistry Associate Professor Professor 1/1/2012 $159,040 4 Health Affairs Yanping Zhang Radiation Oncology Associate Professor Professor 3/1/2012 $165,000 5 Academic Affairs Francesca Talenti Communication Studies Associate Professor Professor 1/1/2012 $83,525 6 Health Affairs Dirk Dittmer Microbio. & Immun. Associate Professor Professor 1/1/2012 $153,000 Reappointments to the Same Rank 1 Health Affairs Anne Sanders Dental Ecology Assistant Professor Assistant Professor 3/1/2013 $90,000 2 Health Affairs Angelique Whitehurst Pharmacology Assistant Professor Assistant Professor 1/1/2013 $102,000 3 Academic Affairs Ann Anderson Government Assistant Professor Assistant Professor 2/1/2013 $101,000 4 Academic Affairs Chotibhak Jotikasthira Business School Assistant Professor Assistant Professor 1/1/2013 $187,000 5 Academic Affairs Sol Sean Wang Business School Assistant Professor Assistant Professor 7/1/2013 $180,000 6 Academic Affairs Gina Chowa Social Work Assistant Professor Assistant Professor 1/1/2013 $101,000 7 Academic Affairs Bradley Staats Business School Assistant Professor Assistant Professor 7/1/2013 $142,000 Actions Conferring Tenure Promotion Conferring Tenure 1 Academic Affairs Christopher Bingham Business School Assistant Professor Associate Professor with Tenure 7/1/2012 $158,000 Reappointment Conferring Tenure 1 Academic Affairs Katrijn Gielens Business School Assoc. Prof. w/out tenure Associate Professor with Tenure 1/1/2012 $166,000 New Appointments Conferring Tenure 1 Academic Affairs Kathy Perkins Dramatic Art N/A Professor 1/1/2012 $95,000 2 Academic Affairs Lora Cohen-Vogel School of Education Vstg. Adj. Assoc. Professor Associate Professor with Tenure 1/1/2012 $127,500 Designation/Reappointments to Distinguished Professorships 1 Health Affairs Margaret E. Bentley Nutrition Professsor Chamblee Distinguished Professor 1/1/2012 $181,283 2 Health Affairs Marilyn Oermann School of Nursing Professor & Div. Chair Fox Term Professor 1/1/2012- $150,386 12/31/2014 3 Health Affairs Mi-Kyung Song School of Nursing Associate Professor Beerstecher-Blackwell Term Scholar 1/1/2012- $92,640 12/31/2014 4 Health Affairs Cass Miller Environmental Sciences and Professsor Okun Distinguished Professor 1/1/2012 $162,828 Engineering 5 Health Affairs Nancy Thomas Dermatology Professsor Irene T. & Robert Alan Briggaman 12/16/2012- $269,260 Distinguished Professor 12/15/2016 24 Total Page 1 The University of North Carolina at Chapel Hill Appendix B EXECUTIVE SUMMARY Board of Trustees December 5, 2011 Requested Increase Percent of Current No. College/Division Name Department/School Rank Reason Amount Increase Salary New Salary Effective Date Compensation Actions 1 Health Affairs Debra Kemp Pharmacy Clin. Asst. Professor Retention $12,584 14.90% $84,460 $97,044 1/14/2012 2 Health Affairs Craig Lee Pharmacy Assistant Professor Retention $13,959 14.90% $93,688 $107,647 1/14/2012 3 Academic Affairs William Rivenbark Government Professor/Director Additional Duties $15,000 12.13% $123,680 $138,680 1/14/2012 Total Monetary Value of Non- Duration of Salary Non-Salary Effective No. College/Division Name Department/School Rank Reason Compensation Compensation Date End Date Non-Salary Compensation Actions 1 N/A N/A N/A N/A N/A N/A N/A N/A N/A NA Page 2 The University of North Carolina at Chapel Hill Appendix C EXECUTIVE SUMMARY Board of Trustees December 5, 2011 No. College/Division Name Department/School Rank Description For Information Page 3 To: Heather Galvan From: Members of the Board of Trustees Fax: (919) 962-1647 Pages: 1 (including cover sheet) Date: December 14, 2011 Re: Mail Ballot, dated December 13, 2011 Trustees: Attached for your review and approval is a special personnel mail ballot. This mail ballot will be approved as part of the Consent Agenda at the Full Board meeting on Thursday, January 26, 2012. The undersigned votes as follows with respect to the recommendations proposed in Chancellor Thorp’s letter dated, December 13, 2011. Approve Disapprove Appendix A, Personnel Actions NO ITEMS Appendix A, Actions Conferring Tenure Appendix B, Compensation Actions Appendix C, For Information Does not need approval ______Signed ______Date Please fax to Heather Galvan at (919) 962-1647. The University of North Carolina at Chapel Hill Appendix A EXECUTIVE SUMMARY Board of Trustees December 13, 2011 Effective No. College/Division Name Dept./School Current Rank New Rank Date Salary Personnel Actions Total Page 1 The University of North Carolina at Chapel Hill Appendix B EXECUTIVE SUMMARY Board of Trustees December 13, 2011 Requested Increase New No. College/Division Name Department/School Rank Reason Amount Current Salary Salary Compensation Actions 1 Health Affairs Barry Popkin Public Health Dist. Professor Retention $8,118 $266,882 $275,000 Total Monetary Value of Non- Duration of Salary Non-Salary Effective No. College/Division Name Department/School Rank Reason Compensation Compensation Date Non-Salary Compensation Actions 1 N/A N/A N/A N/A N/A N/A N/A Page 2 The University of North Carolina at Chapel Hill Appendix C.1 EXECUTIVE SUMMARY Board of Trustees December 13, 2011 For Information - Personnel Corrections No. College/Division Name Rank Effective Date Salary Salary Correction from the December 2011 BOT Agenda 1 Health Affairs *Yanping Zhang Professor 1/1/2012 $180,000 Start Date Correction from the December 2011 BOT Agenda 1 Health Affairs *Yanping Zhang Professor 1/1/2012 $180,000 Page 4 ATTACHMENT J Comprehensive Annual Financial Report UNC - CHAPEL HILL INTERNAL AUDIT DEPARTMENT SUMMARIES OF AUDIT PROJECTS COMPLETED AND IN PROCESS AUGUST 29 TO DECEMBER 4, 2011 Debt Service Function – analysis and testing of processes relating to the university’s debt management activities. No significant issues identified. (complete) Dining Services – a financial, compliance, and operational review of systems and processes used to bill departments for catering services, to allocate dining services revenue to appropriate periods, and to moni- tor and reconcile billings from Aramark, the dining services provider. Noted the need to reconcile Auxil- iary Services’ Gold System to the university’s general ledger, for additional PeopleSoft management re- ports and better monitoring of past due accounts, and for more timely escheatment of inactive balances. We also found an unresolved sales tax balance and the possible need for Form 1099-K reporting. (com- plete) Injury Prevention Resource Center – a financial, compliance, and operational review of the Center re- quested by management in connection with an upcoming change in management of the Center. Since the Center is funded primarily by grants, we focused primarily on research administration issues such as time and effort reporting and allowablity of transactions. No significant findings. (complete) Sponsored Research Billing and Receivables – a financial, operational, and compliance review of pro- cesses used to ensure accurate, timely billing of funds due from sponsors of research projects and prompt collection of these billings. Have identified the need to for more timely billing and follow-up, for better guidance regarding what costs posting after the end of a project can be billed, for a review and reconcilia- tion of account activity prior to sending the final bill, and for more timely closeout of award accounts. (in process) Independent Contractor Function – a financial, compliance, and operational review of processes used to retain and pay independent contractors and to determine whether individuals should be paid as contrac- tors or employees for services performed. (in process) Gene Therapy Research Center – a financial, compliance, and operational review of activities in the Vector Core Facility. Requested by university management to determine if activities in the Facility were being managed in keeping with recharge center procedures and other requirements. (in process) Executive Director for the Arts – financial and compliance review of revenue procedures in the depart- ment, requested by department management. (in process) Point to Point Review – referral from the Office of the State Auditor. An operational review of staffing and scheduling for the University’s disability, evening, late night, and on demand transportation service. (in process). UNC - CHAPEL HILL INTERNAL AUDIT DEPARTMENT SUMMARIES OF AUDIT PROJECTS COMPLETED AND IN PROCESS AUGUST 29 TO DECEMBER 4, 2011 – PAGE 2 Facilities Services Time – review of processes used to maintain information in the Facilities Services billing system and to reconcile that information with the Time Information Management system. (in pro- cess) School of Dentistry – a routine financial, compliance, and operational review of fiscal processes in the School. Added to 2012 audit schedule. (in process) Women’s Studies – a financial, compliance, and operational review of the department; requested by management. (in process) UNC FIT (Financial Improvements and Transformation) – mandatory audit processes established by UNC General Administration as part of process improvement initiatives and reporting requirements. (on- going). Enterprise Resource Planning – advisory assistance to teams implementing modules of the new enter- prise information technology systems. (on-going) HIPPA Security Liaison, SS# Management and Advisory Committee, Enterprise Risk Management Committee, and IT Governance Committee – advisory work done to assist management with identify- ing and managing risks. (on-going) UNC Internal Audit Use of Audit Resources Fiscal Year 2012 - as of December 4, 2011 Pro-Rated Hours Budgeted Budgeted Budget -1- Charged Variance Percent Total Hours Available 12,480 5,280 Less: Leave Hours (1,884) (797) 739 (58) Less: Other Administrative Time -2- (1,920) (812) 496 (316) Total for Leave & Administrative 3,804 1,609 1,235 (374) 30.5% Hours Available for Projects 8,676 3,671 Routine Audits 3,770 1,595 2,866 (1,271) 30.2% Annual Projects & Audit Related 2,200 931 696 235 17.6% Special Reviews & Requests 2,700 1,142 682 460 21.6% Total Scheduled/Charged 8,670 3,668 4,244 (576) Under/ -1- = pro-rated for 22 weeks -2- = training and professional development, staff meetings, professional reading, etc. UNC Internal Audit 2011/12 Audit Schedule Status at 12/4/11 Routine Audits Complete Debt Service Function Auxiliary Services Contracts/Meal Plans Injury Prevention Resource Center In Process Independent Contractor Function OSR Billing and Recivables Gene Therapy Center Executive Director for the Arts School of Dentistry Scheduled University-wide Follow Up 2nd Follow-up for State IT Audit Payment Card Security Monitoring Annual Projects Complete NCAA Assistance - 2011 Scheduled UNC FIT Enterprise Resource Planning Surprise Cash Counts - 2012 Data Security Audit Related In Process Continuous Auditing HIPAA Security Liaison Social Security Number Advisory Committee Enterprise Risk Management Committee C&G Task Force IT Governance Committee Office System Enhancements Audit Related Pool Special Projects & Management Requests In Process Point-to-Point Facilities Services Time Women's Studies Other Internal Consulting - 15 projects T h e new england journal o f medicine ombination antiretroviral thera- de Janeiro and Porto Alegre, Brazil; Pune and Chen- py decreases the replication of human im- nai, India; Chiang Mai, Thailand; and Boston). A munodeficiency virus type 1 (HIV-1) and pilot phase started in April 2005, and enrollment C 1,2 improves the survival of infected persons. Such took place from June 2007 through May 2010. Cou- therapy has been shown to reduce the amount of ples were required to have had a stable relation- HIV-1 in genital secretions.3-5 Because the sexual ship for at least 3 months, to have reported three transmission of HIV-1 from infected persons to or more episodes of vaginal or anal intercourse their partners is strongly correlated with concentra- during this time, and to be willing to disclose their tions of HIV-1 in blood6 and in the genital tract,7 it HIV-1 status to their partner. Patients with HIV-1 has been hypothesized that antiretroviral therapy infection were eligible if their CD4 count was be- could reduce sexual transmission of the virus. Sev- tween 350 and 550 cells per cubic millimeter and eral observational studies have reported decreased they had received no previous antiretroviral therapy acquisition of HIV-1 by sexual partners of patients except for short-term prevention of mother-to-child receiving antiretroviral therapy.8-11 These results transmission of HIV-1. (Full criteria for inclusion have been extrapolated to suggest that the use of and exclusion are provided in the Supplementary early antiretroviral therapy could reduce the spread Appendix, available with the full text of this article of the virus in a population.12 Some ecologic stud- at NEJM.org.) ies have shown a reduction in the incidence of new The study protocol, which is also available at cases of HIV-1 after expanded use of antiretroviral NEJM.org, was approved by at least one local insti- therapy.13,14 tutional review board affiliated with each site, by The effect of the timing of the initiation of boards affiliated with collaborating organizations, antiretroviral therapy on clinical and microbiologic and by other local regulatory bodies when appro- outcomes has been controversial in evaluations priate (for details, see the Supplementary Appen- of the benefit of therapy and of the associated dix). All study participants provided written in- short- and long-term complications and costs. For formed consent in their local languages, or English, many years, antiretroviral therapy was delayed un- if preferred. til a patient’s CD4 count fell below 200 cells per cubic millimeter, which led to frequent opportu- Study Oversight nistic infections.15 Retrospective analyses of pa- The study was funded by the National Institute of tients with HIV-1 infection who were treated in Allergy and Infectious Diseases (NIAID) of the developed countries have suggested a benefit from National Institutes of Health, which assumed all early antiretroviral therapy,16-18 although the abil- sponsor responsibilities through an investigation- ity to control for bias in these studies has limits. al new drug application with the Food and Drug To evaluate the effect of combination antiretro- Administration (FDA). The antiviral agents that viral therapy on the prevention of HIV-1 transmis- were used in the study were donated by pharma- sion to uninfected partners and on clinical events ceutical companies, which were not involved in the in infected persons, the HIV Prevention Trials Net- design or management of the study. All authors work (HPTN) conducted a multicontinent, ran- vouch for the completeness and accuracy of the domized, controlled trial, called HPTN 052, to data presented, as well as the fidelity of the report compare early versus delayed antiretroviral ther- to the study protocol. apy for patients with HIV-1 infection who had CD4 counts between 350 and 550 cells per cubic Study Design millimeter and who were in a stable sexual rela- HIV-1 serodiscordant couples were randomly as- tionship with a partner who was not infected. signed in a 1:1 ratio to either an early or delayed strategy for receipt of antiretroviral therapy. Per- Methods muted-block randomization was used with strat- ification according to site. In the early-therapy Study Population group, antiretroviral therapy was initiated in the We enrolled HIV-1 serodiscordant couples at 13 sites partner with HIV-1 infection at enrollment. In the in 9 countries (Gaborone, Botswana; Kisumu, Ke- delayed-therapy group, therapy was initiated after nya; Lilongwe and Blantyre, Malawi; Johannesburg two consecutive measurements in which the CD4 and Soweto, South Africa; Harare, Zimbabwe; Rio count was 250 cells per cubic millimeter or less or 2 10.1056/nejmoa1105243 nejm.org Prevention of HIV-1 Infection after the development of an illness related to the Antiretroviral Drugs acquired immunodeficiency syndrome (AIDS). Study drugs included a combination of lamivudine HIV-1–infected participants who had active tuber- and zidovudine (Combivir), efavirenz, atazanavir, culosis were excluded, and isoniazid prophylaxis nevirapine, tenofovir, lamivudine, zidovudine, di- was available, according to local guidelines and danosine, stavudine, a combination of lopinavir practice standards. and ritonavir (Kaletra and Aluvia), ritonavir, and a After enrollment, study participants were asked combination of emtricitabine and tenofovir (Tru- to attend three monthly visits, which were fol- vada). A prespecified combination of these drugs lowed by quarterly visits unless they became ill was provided to participants at monthly or quar- or needed additional antiretroviral medications. terly visits. Sites could also use locally supplied, HIV-1–infected participants who were receiving FDA-approved drugs if they could be purchased antiretroviral therapy had one additional visit with nonstudy funds. For participants with viro- 2 weeks after starting therapy. HIV-1–uninfected logic failure, specified second-line treatment regi- partners were encouraged to return for all visits mens were provided. together for counseling on risk reduction and the use of condoms, for treatment of sexually Assessment of Linkage of Seroconversions transmitted infections, and for management of To assess whether seroconversions were linked, other medical conditions. Some HIV-1–infected HIV-1 pol gene sequences were generated by pop- participants received trimethoprim–sulfamethoxa ulation sequencing for study-partner pairs and for zole prophylaxis, according to local guidelines. 10 additional HIV-infected local control subjects for HIV-1–uninfected partners were tested for each relevant site. Sequences were analyzed with HIV-1 seroconversion on a quarterly basis. Samples the use of phylogenetic methods. The probability from all seroconversion events were evaluated at a of linkage was also assessed with the use of central laboratory, and results were reviewed by an Bayes’ theorem to compare the genetic similarity independent HIV end-point committee. Partners of HIV-1 from partner pairs with the genetic sim- with seroconversion were released from the study ilarity of HIV-1 from local control subjects. In some and referred to a prearranged local clinic for care. cases, HIV-1 samples from partner pairs were ana- After the initiation of antiretroviral therapy, lyzed with the use of ultra-deep pyrosequencing virologic failure for HIV-1–infected participants of the gp41 region.19 was defined as two consecutive plasma HIV-1 RNA measurements of more than 1000 copies per mil- Statistical Analysis liliter at 16 weeks or later. Assessment for clinical We determined that an enrollment of 1750 sero- signs and symptoms, laboratory measurements, discordant couples would provide a power of at interviews about sexual behavior, review of ad- least 87% to detect a 39% reduction in the inci- herence to the antiretroviral regimen (including dence of HIV-1 transmission to uninfected part- a self-reported questionnaire and pill counts), and ners in the early-therapy group, as compared with adherence counseling were conducted at each visit. the delayed-therapy group (primary prevention end (Details regarding study procedures, including point). By the end of the trial, we anticipated a guidelines for adherence counseling, are provided total of 188 transmission incidences, with cumu- in the Supplementary Appendix.) lative incidence rates of 8.3% in the early-therapy Any woman who was pregnant at enrollment group and 13.2% in the delayed-therapy group, for or became pregnant was provided antiretroviral a total duration of 6.5 years, with an accrual peri- therapy appropriate for use during pregnancy at od of 1.5 years and a 5% annual loss to follow-up. the start of the second trimester. On the basis of The sample size of 1750 would also provide a pow- the judgment of the site investigator, women in the er of 92% to show that early initiation of antiret- delayed-therapy group discontinued antiretrovi- roviral therapy provided at least a 20% reduction ral therapy after delivery or when breast-feeding in the rate of serious clinical events associated with ended. A new partner could be enrolled with an HIV-1 infection, which included death, a World HIV-1–infected participant if the original partner Health Organization (WHO) stage 4 event, or a se- was released from the study and the new HIV-1– vere bacterial infection or pulmonary tuberculosis uninfected partner met all inclusion or exclusion (primary clinical end point). By the end of the trial, criteria. we anticipated a total of 234 such clinical events, 10.1056/nejmoa1105243 nejm.org 3 T h e new england journal o f medicine with cumulative incidence rates of 8.7% in the The majority of couples (97%) were heterosex- early-therapy group and 18.0% in the delayed- ual, and 94% were married; 50% of HIV-1–infected therapy group. participants were men. The majority of partici- The study was reviewed twice each year by an pants (61%) were between 26 and 40 years of age. independent NIAID multinational data and safe- At enrollment, 1291 of HIV-1–infected participants ty monitoring board. To guide the board in its (73%) and 1281 of HIV-1–uninfected partners recommendations regarding trial continuation, a (72%) reported having had at least one sexual composite monitoring end point was developed to encounter during the previous week. During the include the occurrence of either death or WHO same period, 7% and 8%, respectively, reported stage 4 events (excluding esophageal candidiasis) having unprotected sex. The median CD4 counts in HIV-1–infected participants or the transmission for the HIV-1–infected partners were 442 cells per of HIV-1 to uninfected partners, whichever oc- cubic millimeter in the early-therapy group and curred first in the discordant couple. These were 428 cells per cubic millimeter in the delayed-ther- the events that were considered to have the great- apy group. The median log10 plasma viral load est clinical effect on both the HIV-1–infected par- was 4.4 in each study group. Participants in ticipant and the uninfected partner. A Lan–DeMets the two study groups were similar in educational implementation of an O’Brien–Fleming monitor- status, self-reported sexual behavior, and rate of ing boundary was used to evaluate the interim data condom use (Table 1). with respect to this composite end point.20,21 An At enrollment, less than 5% of participants had early termination would be indicated if there were a sexually transmitted infection, and rates and conclusive evidence to rule out a hazard ratio of types of infection were similar in the two study 0.80 or more in the early-therapy group. Interim groups (see the Supplementary Appendix). A to- analyses were planned when approximately 25%, tal of 84 of 449 HIV-uninfected male partners 50%, 75%, and 100% of a total 340 composite (19%) in the early-therapy group and 64 of 460 events were observed. (14%) in the delayed-therapy group had been cir- We used the Kaplan–Meier method to calculate cumcised (P = 0.05). New sexually transmitted in- event-free probabilities and person-year analysis for fections were detected with similar frequency incidence rate for a given year. We also used Cox among participants in the early-therapy group and regression to estimate relative risks, which were the delayed-therapy group during the study, with expressed as hazard ratios and 95% confidence 36 and 34 syphilis infections, 6 and 8 gonorrhea intervals, and to provide adjustment for potential infections, 10 and 11 chlamydia infections, and prognostic factors, such as the infected partici- 22 and 19 trichomonas infections, respectively. pant’s baseline CD4 count, baseline plasma HIV- Among HIV-1–infected participants, a mean of 1 RNA concentration, and sex. The same Cox 96% of those in the early-therapy group and 95% analyses were performed on linked transmis- of those in the delayed-therapy group reported sions, any transmissions, clinical events, and com- 100% condom use during the study. posite monitoring events. We used chi-square tests On April 28, 2011, the data and safety moni- to compare the frequencies of adverse events. A toring board recommended that the results of the P value of less than 0.05 was considered to indi- study be released on the basis of data collection cate statistical significance. The cutoff was ad- through February 21, 2011. At that time, 90% of justed for multiple comparisons in trial-monitoring couples remained enrolled in the study, with a boundaries. median follow-up of 1.7 years; the total number of person-years of follow-up was 1585 in the early- Results therapy group and 1567 in the delayed-therapy group. The expected effect of early versus delayed Study Participants antiretroviral therapy on log10 plasma viral load A total of 10,838 persons were screened in order and CD4 counts in the HIV-1–infected participants to enroll 1763 HIV-1–serodiscordant couples; 886 was observed shortly after enrollment. By 3 months couples were randomly assigned to the early-ther- after randomization, 89% of the participants in apy group and 877 to the delayed-therapy group) the early-therapy group had a plasma viral load of (Fig. 1, and the Supplementary Appendix). Twelve less than 400 copies per milliliter, as compared additional HIV-1–uninfected partners were enrolled with 9% in the delayed-therapy group. CD4 counts as the result of a new relationship. in the early-therapy group rose after the initia- 4 10.1056/nejmoa1105243 nejm.org Prevention of HIV-1 Infection 10,838 Patients were screened 7312 Were excluded 3058 Were HIV-positive but were ineligible owing to CD4 count 2565 Were HIV-negative but HIV-positive partner was ineligible 308 Were HIV-positive with HIV-positive partner 155 Were ineligible owing to sexual history 1226 Had other reason 3526 Were identified as 1763 eligible HIV-serodiscordant couples 1763 Couples underwent randomization (including 82 couples from run-in study) 886 Couples were assigned 877 Couples were assigned to early-therapy group to delayed-therapy group 7 New partners were 5 New partners were enrolled enrolled 893 Partners were enrolled for HIV-1 882 Partners were enrolled for HIV-1 transmission analysis transmission analysis 2 Partners were HIV- 2 Partners were HIV- positive at enrollment positive at enrollment Semiannual-visit attendance Semiannual-visit attendance Month 6 809/874 93% Month 6 803/873 92% Month 12 720/800 90% Month 12 727/800 91% Month 18 509/601 85% Month 18 535/612 87% Month 24 340/393 87% Month 24 346/399 87% Month 30 230/267 86% Month 30 231/267 87% Month 36 113/129 88% Month 36 122/135 90% Month 42 43/50 86% Month 42 49/54 91% 22 (2%) Couples had no follow-up 31 (4%) Couples had no follow-up 5 (1%) Had a partner who died 4 (<1%) Had a partner who died 9 (1%) Declined further participation 13 (1%) Declined further participation 1 (<1%) Was unable to adhere to 3 (<1%) Were unable to adhere to visit schedule visit schedule 3 (<1%) Relocated 3 (<1%) Relocated 2 (<1%) Were unable to be contacted 2 (<1%) Were unable to be contacted 31 (3%) Ended relationship 42 (5%) Ended relationship 4 (<1%) Had other reason 1 (<1%) Had other reason Figure 1. Enrollment and Outcomes. This trial profile describes recruitment of couples from the general population, randomization, HIV-1–uninfected partner’s enrollment, seroconversion at baseline, retention, and loss-to-follow-up for assessment of the primary end point of linked HIV-1 transmission. Enrolled partners were followed on a quarterly-visit schedule, although atten- dance at semiannual visits is shown. 10.1056/nejmoa1105243 nejm.org 5 T h e new england journal o f medicine tion of antiretroviral therapy, from a median of per cubic millimeter at enrollment to 399 cells per 442 cells per cubic millimeter at enrollment to cubic millimeter by 12 months. A total of 21% of 603 cells per cubic millimeter by 12 months, and HIV-1–infected participants in the delayed-therapy the counts continued to rise throughout the follow- group began taking antiretroviral therapy after up period (see the Supplementary Appendix). A a median of 42 months. Among all participants, modest decline in CD4 counts was observed in the 72% received a combination of zidovudine, lamivu- delayed-therapy group, from a median of 428 cells dine, and efavirenz (see the Supplementary Appen- Table 1. Baseline Characteristics of the Participants.* Characteristic HIV-1–Infected Participants HIV-1–Uninfected Participants† Early Therapy Delayed Therapy Early Therapy Delayed Therapy (N = 886) (N = 877) (N = 893) (N = 882) Demographic Female sex — no. (%) 432 (49) 441 (50) 441 (49) 418 (47) Age group — no. (%) 18–25 yr 145 (16) 161 (18) 154 (17) 174 (20) 26–40 yr 556 (63) 547 (62) 537 (60) 526 (60) >40 yr 185 (21) 169 (19) 202 (23) 182 (21) Education level — no. (%) No schooling 101 (11) 69 (8) 112 (13) 77 (9) Primary schooling 360 (41) 347 (40) 317 (35) 344 (39) Secondary schooling 346 (39) 388 (44) 373 (42) 367 (42) Postsecondary schooling 79 (9) 72 (8) 91 (10) 93 (11) Missing data 0 1 (<1) 0 1 (<1) Marital status — no. (%) Single 49 (6) 38 (4) 53 (6) 43 (5) Married or living with partner 833 (94) 833 (95) 834 (93) 833 (94) Widowed, separated, or divorced 4 (<1) 6 (1) 6 (1) 6 (1) Region — no. (%) North or South America 142 (16) 136 (16) 145 (16) 139 (16) Asia 267 (30) 264 (30) 268 (30) 264 (30) Africa 477 (54) 477 (54) 480 (54) 479 (54) Sexual activity — no. (%) Any unprotected sex in past week 37 (4) 51 (6) 49 (5) 53 (6) No. of sex partners in past 3 mo 0–1 831 (94) 833 (95) 863 (97) 844 (96) 2–4 48 (5) 41 (5) 29 (3) 36 (4) >4 7 (1) 2 (<1) 1 (<1) 1 (<1) Missing data 0 1 (<1) 0 1 (<1) No. of sexual encounters in past week 0 246 (28) 225 (26) 253 (28) 240 (27) 1–2 430 (49) 438 (50) 410 (46) 433 (49) 3–4 156 (18) 158 (18) 180 (20) 151 (17) >4 54 (6) 55 (6) 50 (6) 57 (6) Missing data 0 1 (<1) 0 1 (<1) 6 10.1056/nejmoa1105243 nejm.org Prevention of HIV-1 Infection Table 1. (Continued.) Characteristic HIV-1–Infected Participants HIV-1–Uninfected Participants† Early Therapy Delayed Therapy Early Therapy Delayed Therapy (N = 886) (N = 877) (N = 893) (N = 882) Clinical CD4 count — no./mm3 Median 442 428 Interquartile range 373–522 357–522 NA NA Plasma RNA viral load — no. (%) <400 copies/ml 54 (6) 43 (5) NA NA 400–1000 copies/ml 24 (3) 33 (4) NA NA 1001–10,000 copies/ml 212 (24) 183 (21) NA NA 10,001–100,000 copies/ml 407 (46) 432 (49) NA NA 100,001–1 million copies/ml 186 (21) 186 (21) NA NA Missing data 3 (<1) 4 (<1) NA NA Women reporting previous antiretroviral 115/432 (27) 119/441 (27) NA NA therapy during pregnancy — no./total no. (%) Type of serodiscordancy — no. (%) HIV-positive man, HIV-negative woman 436 (49) 417 (48) NA NA HIV-positive woman, HIV-negative man 431 (49) 441 (50) NA NA HIV-positive man, HIV-negative man 18 (2) 19 (2) NA NA HIV positive woman, HIV-negative 1 (<1) 0 NA NA woman * Data regarding the incidence of sexually transmitted infections are provided in the Supplementary Appendix. HIV denotes human immunodeficiency virus, and NA not applicable. † Some participants with HIV-1 infection had more than one uninfected partner during the study period. dix). Adherence to the study regimen of more than 35 events in the delayed-therapy group (incidence 95% (as measured by pill count) was observed in rate, 2.2 per 100 person-years; 95% CI, 1.6 to 3.1), 79% of participants in the early-therapy group and for a hazard ratio in the early-therapy group of in 74% of those in the delayed-therapy group. 0.11 (95% CI, 0.04 to 0.32; P<0.001) (Table 2 and Details with respect to regimens of antiretroviral Fig. 2; also see the Supplementary Appendix for therapy and pill counts are provided in the Sup- details regarding the incidence of transmission). plementary Appendix. Through viral genetic analysis, 28 transmissions Virologic failure was observed in 45 of 886 were linked to the HIV-1–infected participant (in- participants (5%) in the early-therapy group and cidence rate, 0.9 per 100 person-years; 95% CI, in 5 of 184 participants in the delayed-therapy 0.6 to 1.3), with 1 transmission in the early-therapy group who initiated antiretroviral therapy (3%) group (incidence rate, 0.1 per 100 person-years; (P = 0.23). Of all treated participants, 66% initiated 95% CI, 0.0 to 0.4) and 27 transmissions in the a second-line regimen. delayed-therapy group (incidence rate, 1.7 per 100 person-years; 95% CI, 1.1 to 2.5), for a hazard Primary Prevention Outcome ratio in the early-therapy group of 0.04 (95% CI, A total of 39 HIV-1 transmission events were ob- 0.01 to 0.27; P<0.001). The remaining 11 trans- served (incidence rate, 1.2 per 100 person-years; missions (3 in the early-therapy group and 8 in the 95% confidence interval [CI], 0.9 to 1.7), with delayed-therapy group) included 7 transmissions 4 events in the early-therapy group (incidence rate, that were unlinked (3 in the early-therapy group 0.3 per 100 person-years; 95% CI, 0.1 to 0.6) and and 4 in the delayed-therapy group), 3 transmis- 10.1056/nejmoa1105243 nejm.org 7 T h e new england journal o f medicine Table 2. Incidence of Partner-Linked and Any HIV-1 Transmission and Clinical and Composite Events. Hazard or Rate Ratio Variable Early Therapy Delayed Therapy (95% CI)* Rate Rate Events Person-yr (95% CI) Events Person-yr (95% CI) no. % no. % Linked transmission Total 1 1585.3 0.1 (0.0–0.4) 27 1567.3 1.7 (1.1–2.5) 0.04 (0.01–0.27) 1 yr 1 819.0 0.1 (0.0–0.7) 16 813.3 2.0 (1.1–3.2) 0.06 (0.00–0.40) 2–3 yr 0 686.5 0.0 (0.0–0.5) 9 682.8 1.3 (0.6–2.5) 0.00 (0.00–0.50) >3 yr 0 79.9 0.0 (0.0–4.6) 2 71.2 2.8 (0.3–10.1) 0.00 (0.00–4.75) Any transmission† Total 4 1585.3 0.3 (0.1–0.6) 35 1567.3 2.2 (1.6–3.1) 0.11 (0.04–0.32) 1 yr 2 819.0 0.2 (0.0–0.9) 18 813.3 2.2 (1.3–3.5) 0.11 (0.01–0.46) 2–3 yr 2 686.5 0.3 (0.0–1.1) 14 682.8 2.1 (1.1–3.4) 0.14 (0.02–0.62) >3 yr 0 79.9 0.0 (0.0–4.6) 3 71.2 4.2 (0.9–12.3) 0.00 (0.00–2.16) Clinical events‡ Total 40 1661.9 2.4 (1.7–3.3) 65 1641.8 4.0 (3.1–5.0) 0.59 (0.40–0.88) 1 yr 29 831.0 3.5 (2.3–5.0) 39 832.6 4.7 (3.3–6.4) 0.75 (0.44–1.24) 2–3 yr 9 739.8 1.2 (0.6–2.3) 21 725.7 2.9 (1.8–4.4) 0.42 (0.17–0.96) >3 yr 2 91.1 2.2 (0.3–7.9) 5 83.6 6.0 (1.9–14.0) 0.37 (0.04–2.24) Composite events§ Total 23 1700.1 1.4 (0.9–2.0) 79 1642.0 4.8 (3.8–6.0) 0.27 (0.17–0.42) 1 yr 13 843.7 1.5 (0.8–2.6) 47 833.9 5.6 (4.1–7.5) 0.27 (0.14–0.51) 2–3 yr 8 763.8 1.0 (0.5–2.1) 26 732.5 3.5 (2.3–5.2) 0.30 (0.12–0.67) >3 yr 2 92.6 2.2 (0.3–7.8) 6 75.5 7.9 (2.9–17.3) 0.27 (0.03–1.52) * Hazard ratios were calculated with the use of unstratified univariate Cox regression analysis on an intention-to-treat basis. Year-specific rate ratios were calculated on the basis of the person-year analysis. P<0.001 for the between-group comparison for linked transmission, P<0.001 for all transmission, P = 0.01 for clinical events, and P<0.001 for composite events, with all comparisons favoring early therapy. † Any transmission includes all transmission events observed during follow-up, regardless of their linkage between partners. ‡ Clinical events include death, World Health Organization stage 4 events, severe bacterial infections, and pulmonary tuber- culosis for index partners. § Composite events include death or World Health Organization stage 4 events (excluding esophageal candidiasis) for the index partner or HIV transmission to the uninfected partner, whichever occurred earlier. sions that could not be classified on the basis of group was identified 3 months after the HIV-1– available data, and 1 transmission that has not yet infected participant initiated treatment; all linked been evaluated. The latter 4 transmissions were transmissions in the delayed-therapy group oc- all in the delayed-therapy group. curred while the HIV-1–infected participant was The rate of transmission events in the delayed- not receiving antiretroviral therapy. The Kaplan– therapy group was relatively constant across the Meier curves for both linked and any transmis- first 3 years of study follow-up for both linked sions show immediate and sustained reduction in and any transmissions. Of the 28 HIV-1–infected the risk of HIV-1 transmission after the initiation participants who had linked transmission to a of antiretroviral therapy (Fig. 2). partner, 17 (61%) had a CD4 count of more than Of the 28 linked transmissions, 23 (82%) oc- 350 cells per cubic millimeter at the study visit curred at African sites. HIV-1–infected women before the detection of linked HIV-1 transmission. were the source of infection in 18 of 27 (67%) The single linked transmission in the early-therapy linked transmissions in the delayed-therapy group, 8 10.1056/nejmoa1105243 nejm.org Prevention of HIV-1 Infection A Linked HIV Transmission B Any HIV Transmission 1.0 0.3 1.0 0.3 0.8 0.2 0.8 0.2 Delayed 0.6 Delayed 0.6 0.1 0.1 Early 0.4 Early 0.4 0.0 0.0 0 1 2 3 4 5 0 1 2 3 4 5 Cumulative Probability Cumulative Probability 0.2 0.2 0.0 0.0 0 1 2 3 4 5 0 1 2 3 4 5 Years since Randomization Years since Randomization No. at Risk No. at Risk Early 893 658 298 79 31 24 Early 893 658 298 79 31 24 Delayed 882 655 297 80 26 22 Delayed 882 655 297 80 26 22 C Clinical Event D Composite Event 1.0 0.3 1.0 0.3 Delayed Delayed 0.8 0.2 0.8 0.2 Early 0.6 0.6 0.1 0.1 Early 0.4 0.4 0.0 0.0 0 1 2 3 4 5 0 1 2 3 4 5 Cumulative Probability Cumulative Probability 0.2 0.2 0.0 0.0 0 1 2 3 4 5 0 1 2 3 4 5 Years since Randomization Years since Randomization No. at Risk No. at Risk Early 886 700 333 85 36 29 Early 886 719 344 90 36 29 Delayed 877 701 317 86 32 25 Delayed 877 702 320 84 28 22 Figure 2. Kaplan–Meier Estimates for Partner-Linked and Any HIV-1 Transmission and for Clinical and Composite Monitoring Events. Shown are Kaplan–Meier estimates for the cumulative probabilities of linked HIV-1 transmission between partners (Panel A), any HIV transmission (Panel B), clinical events (Panel C), and composite monitoring events (Panel D) among participants in the early-therapy and delayed-therapy groups. and a man was the source of the single transmis- ma viral load in 27 participants at the visit most sion in the early-therapy group. Women were the proximal to the detection of HIV-1 transmission HIV-1–infected participant in 58% of African cou- was 4.9 log10 (range, 2.6 to 5.8). Conversely, self- ples. A high viral load in blood plasma of infected reported 100% condom use at baseline was associ- participants at baseline increased the risk of ated with a reduced risk of HIV-1 transmission. In HIV-1 transmission (Table 3). The median plas- the stratified multivariate analysis according to 10.1056/nejmoa1105243 nejm.org 9 T h e new england journal o f medicine Table 3. Hazard Ratios for Prognostic Factors for Partner-Linked and Any HIV-1 Transmission and for Clinical and Composite Events.* Linked Any Clinical Composite Variable Transmission Transmission Events Events hazard ratio (95% CI) Univariate analysis Early therapy vs. delayed therapy 0.04 (0.01–0.26) 0.11 (0.04–0.32) 0.60 (0.41–0.90) 0.28 (0.18–0.45) Baseline CD4 count (per 100 CD4 1.27 (1.02–1.59) 1.25 (1.02–1.52) 0.84 (0.70–1.00) 1.06 (0.91–1.24) increment) Baseline viral load (per unit log10 1.96 (1.17–3.27) 1.66 (1.08–2.55) 1.74 (1.32–2.30) 1.51 (1.15–1.97) increment) Male sex vs. female sex 0.69 (0.31–1. 52) 0.88 (0.45–1.71) 1.61 (1.05–2.48) 1.18 (0.78–1.78) Baseline condom use (100% vs. <100%) 0.35 (0.14–0.88) 0.47 (0.19–1.14) NA 0.68 (0.29–1.60) Multivariate analysis Early therapy vs. delayed therapy 0.04 (0.01–0.28) 0.11 (0.04–0.33) 0.59 (0.40–0.89) 0.28 (0.18–0.45) Baseline CD4 count (per 100 CD4 1.24 (1.00–1.54) 1.22 (1.02–1.47) 0.90 (0.75–1.08) 1.11 (0.96–1.28) increment) Baseline viral load (per unit log10 2.85 (1.51–5.41) 2.13 (1.30–3.50) 1.65 (1.24–2.20) 1.60 (1.21–2.11) increment) Male sex vs. female sex 0.73 (0.33–1.65) 1.00 (0.51–1.97) 1.46 (0.95–2.26) 1.18 (0.78–1.80) Baseline condom use (100% vs. <100%) 0.33 (0.12–0.91) 0.41 (0.16–1.08) NA 0.64 (0.27–1.52) * Hazard ratios were calculated with the use of univariate and multivariate Cox regression analysis, stratified according to study site. The results are similar to those calculated with the use of unstratified Cox regression analysis, which are not shown. NA denotes not applicable. site, the adjusted hazard ratio for linked transmis- early-therapy group and 15 in the delayed-therapy sion in the early-therapy group was 0.04 (95% CI, group; isoniazid prophylaxis was administered 0.01 to 0.28; P<0.001) (Table 3). to only 4% of participants in each study group. There were 23 deaths during the course of the Primary Treatment Outcome study, 10 in the early-therapy group and 13 in the A total of 105 treatment end points, as measured delayed-therapy group (hazard ratio, 0.77; 95% CI, by the first serious HIV-1–related clinical event or 0.34 to 1.76; P = 0.27) (for details regarding causes death, were observed in HIV-1–infected partici- of death, see the Supplementary Appendix). pants: 40 in the early-therapy group and 65 in the delayed-therapy group (hazard ratio, 0.59; 95% CI, Composite Monitoring Events 0.40 to 0.88; P = 0.01 (Table 2, and the Supplemen- Among 102 composite monitoring events, there tary Appendix). Of such clinical events, 44% oc- were 39 transmission events in which the sexual curred in Asia and 45% in Africa. The baseline partner acquired HIV-1. Among HIV-1–infected plasma viral load was an important predictor of participants, 21 died and 42 had WHO stage 4 clin- clinical events, as assessed on multivariate analy- ical events. Of these monitoring events, 58 (57%) sis (Table 3). In the stratified multivariate model, occurred in Africa, 31 (30%) in Asia, and 13 (13%) the adjusted hazard ratio for clinical events in the in the Americas. Overall, 23 monitoring events early-therapy group was 0.59 (95% CI, 0.40 to 0.89). were observed in the early-therapy group and 79 The difference in the rate of clinical events ap- in the delayed-therapy group (hazard ratio, 0.27; peared to be driven mainly by the incidence of 95% CI, 0.17 to 0.42; P<0.001) (Table 2). Accord- extrapulmonary tuberculosis, which developed ing to the monitoring guidelines that were based in 3 participants in the early-therapy group and on the Lan–DeMets implementation of O’Brien– 17 in the delayed-therapy group (P = 0.002); of these Fleming boundaries, the computed z statistic was cases, 55% were observed in India. Pulmonary tu- 4.43, which exceeded the prespecified cutoff of berculosis was observed in 13 participants in the 3.93 and thus ruled out the hypothesis that early 10 10.1056/nejmoa1105243 nejm.org Prevention of HIV-1 Infection therapy would provide at most a 20% reduction in developed countries.22,23 Clade C HIV-1, the domi- the risk of the composite monitoring end point. nant type in southern Africa, may have other trans- mission advantages as well.24 More frequent sexual Adverse Events encounters and limited condom use would also After the exclusion of primary clinical end points favor increased HIV transmission among African (death, WHO stage 4 events, pulmonary tubercu- couples, possibilities that are being evaluated. losis, and severe bacterial infections), 246 HIV-1– Although HIV-1 transmission from patients infected participants had one or more severe or with acute and early HIV-1 infection and advanced life-threatening adverse events (grade 3 or 4): 127 HIV-1 disease and the acquired immunodeficiency of 886 (14%) were in the early-therapy group and syndrome (AIDS)25 appears to be most efficient,26 119 of 877 (14%) were in the delayed-therapy the results from this and other studies9 emphasize group (P = 0.64). The most frequently reported ad- that HIV-1 can be transmitted from infected per- verse events included infections, psychiatric and sons who are asymptomatic or minimally symp- nervous system disorders, metabolism and nutri- tomatic and who have high CD4 counts. Since tion disorders, and gastrointestinal disorders (for most persons with established HIV-1 infection fall details, see the Supplementary Appendix). Grade into the latter category, such transmission, albeit 3 or 4 laboratory abnormalities during study fol- not maximally efficient, must help fuel the spread low-up occurred in 242 participants (27%) in the of HIV-1. early-therapy group and 161 participants (18%) Early antiretroviral therapy was associated with in the delayed-therapy group (P<0.001). The most a relative reduction of 41% in the number of HIV- frequent laboratory abnormalities included neutro- 1–related clinical events, which suggests a clinical penia, abnormal phosphate level, and total biliru- benefit for the initiation of antiretroviral therapy bin elevations (with bilirubin elevations observed when a person has a CD4 count of 350 to 550 cells primarily in participants taking atazanavir as part per cubic millimeter, as compared with therapy of their drug regimen) (see the Supplementary that is delayed until the CD4 count falls into the Appendix). range of 200 to 250 cells per cubic millimeter. In contrast to a recent trial15 comparing the effect of Discussion the initiation of therapy in patients with a CD4 count ranging from 200 to 350 cells per cubic mil- In this study involving 1763 serodiscordant cou- limeter with those with a count below 200 cells ples in which HIV-1–infected participants had a per cubic millimeter, we did not detect a signifi- CD4 count of 350 to 550 cells per cubic millime- cant between-group difference in overall mortality. ter, there was a relative reduction of 96% in the Despite our relatively short follow-up period, the number of linked HIV-1 transmissions resulting magnitude of the clinical effect we observed was from the early initiation of antiretroviral therapy, as similar to that seen in observational studies con- compared with delayed therapy. There was a relative ducted in the developed world.16-18 The difference reduction of 89% in the total number of HIV-1 between the early-therapy group and the delayed- transmissions resulting from the early initiation therapy group was driven largely by the diagnosis of antiretroviral therapy, regardless of viral link- of extrapulmonary tuberculosis, with the majority age with the infected partner. The sustained sup- of these cases occurring in India. The use of iso- pression of HIV-1 in genital secretions resulting niazid prophylaxis, although recommended by the from antiretroviral therapy is the most likely mech- WHO for patients with HIV-1 infection,27 was in- anism for the prevention of HIV-1 transmission that frequently prescribed for participants in this study. we observed.4,5 In addition, data from observational studies fo- The majority of HIV-1 transmissions (82%) were cusing on HIV-1–related and non–HIV-1–related observed in Africa. This result reflects not only the clinical events and CD4 counts have led to the large number of study participants who were en- hypothesis that delayed antiretroviral therapy could rolled in this region (54%) but also other factors ultimately lead to an increased rate of clinical that increase the probability of HIV-1 transmission events, regardless of subsequent therapy.28 How- among African couples. Several groups have re- ever, we cannot evaluate this possibility without a ported higher viral loads in patients with HIV-1 longer period of follow-up. infection in sub-Saharan Africa than in patients in We noted more adverse events in the early- 10.1056/nejmoa1105243 nejm.org 11 T h e new england journal o f medicine therapy group than in the delayed-therapy group, vents HIV-1 transmission over an extended peri- including more adverse events related to antiretro- od of time. In this trial, we found that early anti- viral therapy. The clinical importance of the labo- retroviral therapy had a clinical benefit for both ratory abnormalities that were responsible for this HIV-1–infected persons and their uninfected sexu- difference is unclear. Further examination of these al partners. These results support the use of anti- data and additional longitudinal follow-up will be retroviral treatment as a part of a public health important to better understand the clinical and strategy to reduce the spread of HIV-1 infection. public health benefits of early antiretroviral ther- apy, as compared with drug costs and side effects. Supported by the HIV Prevention Trials Network (HPTN) and Our study has several limitations. In order to by grants (UM1-AI068619 and U01-AI068619; UM1-AI068613 examine the effects of antiretroviral therapy on and U01-AI068613, to the HPTN Network Laboratory; and UM1- HIV-1 transmission, we studied stable HIV-1–dis- AI068617 and U01-AI068617, to the HPTN Statistical and Data Management Center) from the National Institute of Allergy and cordant couples, who may not be entirely repre- Infectious Diseases. Study drugs were donated by Abbott Labo- sentative of the general population.29 We provided ratories, Boehringer Ingelheim, Bristol-Myers Squibb, Gilead ongoing couples counseling and condoms, which Sciences, GlaxoSmithKline, and Merck. Dr. Hosseinipour reports receiving lecture fees from Abbott probably contributed to the low incidence of HIV-1 Virology; Dr. Eshleman, consulting fees from Roche Diagnostics, infection, as previously reported.30 Some partici- lecture fees and samples or laboratory reagents from Abbott Diag- pants received trimethoprim–sulfamethoxazole nostics and Celera Diagnostics, and lecture fees from Monogram Biosciences; Dr. Mills, grant support from GlaxoSmithKline; Dr. and isoniazid prophylaxis at the discretion of the de Bruyn, travel support from Sanofi Pasteur; Dr. Eron, consult- investigators, which could have reduced the de- ing fees and grant support from Merck, Bristol-Myers Squibb, gree of benefit observed with early antiretroviral GlaxoSmithKline, and ViiV Healthcare, consulting fees from 31 Gilead Sciences and Tibotec, and lecture fees from Bristol-Myers therapy. Squibb and Roche; Dr. Gallant, consulting fees from Abbott Lab- In conclusion, the biologic plausibility of the oratories, Bristol-Myers Squibb, Gilead Sciences, Merck, Tibotec use of antiretroviral therapy for the prevention Therapeutics, ViiV Healthcare, GlaxoSmithKline, Pfizer, Sangamo BioSciences, and Koronis, grant support and travel support from of HIV-1 infection has been carefully examined Gilead Sciences, and lecture fees from Monogram Biosciences; during the past two decades.32 The idea of HIV-1 Dr. Havlir, study drug from Abbott; and Dr. Swindells, consult- treatment as prevention has garnered tremendous ing fees from Gilead Sciences and Abbott Diagnostics and grant 33 support from Pfizer, GlaxoSmithKline, and Bristol-Myers interest and hope and inspired a series of pop- Squibb. No other potential conflict of interest relevant to this ulation-level HIV-1 treatment-as-prevention studies article was reported. that are now in the pilot or planning stages.34,35 Disclosure forms provided by the authors are available with the full text of this article at NEJM.org. Such interventions are based on the hypothesis We thank Drs. Wafaa El-Sadr, Quarraisha Abdool Karim, and that the use of antiretroviral therapy reliably pre- Ward Cates for their help in the preparation of the manuscript. Appendix The authors’ affiliations are as follows: the University of North Carolina School of Medicine, Chapel Hill (M.S.C., M.C.H., I.F.H., J.E.); the Vaccine and Infectious Disease Division, Fred Hutchinson Cancer Research Center (Y.Q.C., L.W.), and the University of Washington (T.R.F.) — both in Seattle; Family Health International, Arlington, VA (M.M.), and Durham, NC (T.G.); the UNC Project, Lilongwe (M.C.H.) and the College of Medicine–Johns Hopkins Project, Blantyre (J.K.) — both in Malawi; the Y.R. Gaitonade Center for AIDS Research and Education, Chennai (N.K.), and the National AIDS Research Institute, Pune (S.M., S.V.G.) — both in India; University of Zimbabwe, Harare (J.G.H.); Instituto de Pesquisa Clinica Evandro Chagas, Fiocruz (B.G.), and Hospital Geral de Nova Iguacu and Laboratorio de AIDS e Imunologia Molecular-IOC/Fiocruz (J.H.S.P.) — both in Rio de Janeiro; Research Institute for Health Sciences, Chiang Mai University, Chiang Mai, Thailand (S.C.); Hospital Nossa Senhora da Conceição, Porto Alegre, Brazil (B.R.S.); Fenway Health (K.H.M.) and Harvard School of Public Health (H.R., M.E.) — both in Boston; Johns Hopkins University School of Medicine (S.H.E., E.P.-M., J.G.) and Johns Hopkins Bloomberg School of Public Health (T.E.T., D.C.) — both in Baltimore; Botswana Harvard AIDS In- stitute, Gaborone (J.M.); Centers for Disease Control and Prevention (CDC) Division of HIV/AIDS Prevention, Kenya Medical Research Institute–CDC Research and Public Health Collaboration HIV Research Branch, Kisumu (L.A.M.); Perinatal HIV Research Unit (G.B.) and Department of Medicine (I.S.), University of the Witwatersrand, Johannesburg; University of California, San Francisco, San Fran- cisco (D.H.); University of Nebraska Medical Center, Omaha (S.S.); Division of AIDS, National Institute of Allergy and Infectious Dis- eases, National Institutes of Health, Bethesda, MD (V.E., D.B.); and David Geffen UCLA School of Medicine, Los Angeles (K.N.-S.). 12 10.1056/nejmoa1105243 nejm.org Prevention of HIV-1 Infection References 1. Ray M, Logan R, Sterne JA, et al. The companied by reductions in new HIV in- NK, et al. Rates of HIV-1 transmission per effect of combined antiretroviral therapy fections in San Francisco. PLoS ONE 2010; coital act, by stage of HIV-1 infection, in on the overall mortality of HIV-infected 5(6):e11068. Rakai, Uganda. J Infect Dis 2005;191: individuals. AIDS 2010;24:123-37. 14. Montaner JS, Lima VD, Barrios R, et 1403-9. 2. Braitstein P, Brinkhof MW, Dabis F, et al. Association of highly active antiretro- 26. Powers KA, Poole C, Pettifor AE, al. Mortality of HIV-1-infected patients in viral therapy coverage, population viral Cohen MS. Rethinking the heterosexual the first year of antiretroviral therapy: com- load, and yearly new HIV diagnoses in infectivity of HIV-1: a systematic review parison between low-income and high- British Columbia, Canada: a population- and meta-analysis. Lancet Infect Dis 2008; income countries. Lancet 2006;367:817-24. based study. Lancet 2010;376:532-9. 8:553-63. [Erratum, Lancet 2006;367:1902.] 15. Severe P, Juste MA, Ambroise A, et al. 27. Guidelines for intensified tuberculo- 3. Cohen MS, Gay CL. Treatment to pre- Early versus standard antiretroviral thera- sis case finding and isoniazid preventive vent transmission of HIV-1. Clin Infect Dis py for HIV-infected adults in Haiti. N Engl therapy for people living with HIV in re- 2010;50:Suppl 3:S85-S95. J Med 2010;363:257-65. source constrained settings. Geneva: 4. Graham SM, Holte SE, Peshu NM, et 16. Kitahata MM, Gange SJ, Abraham World Health Organization, 2011. (http:// al. Initiation of antiretroviral therapy leads AG, et al. Effect of early versus deferred whqlibdoc.who.int/publications/2011/ to a rapid decline in cervical and vaginal antiretroviral therapy for HIV on survival. 9789241500708_eng.pdf.) HIV-1 shedding. AIDS 2007;21:501-7. N Engl J Med 2009;360:1815-26. 28. Baker JV, Peng G, Rapkin J, et al. 5. Vernazza PL, Troiani L, Flepp MJ, et al. 17. Sterne JA, May M, Costagliola D, et al. CD4+ count and risk of non-AIDS diseas- Potent antiretroviral treatment of HIV in- Timing of initiation of antiretroviral ther- es following initial treatment for HIV in- fection results in suppression of the semi- apy in AIDS-free HIV-1-infected patients: fection. AIDS 2008;22:841-8. nal shedding of HIV. AIDS 2000;14:117-21. a collaborative analysis of 18 HIV cohort 29. Eyawo O, de Walque D, Ford N, Gakii 6. Quinn TC, Wawer MJ, Sewankambo studies. Lancet 2009;373:1352-63. G, Lester RT, Mills EJ. HIV status in dis- N, et al. Viral load and heterosexual trans- 18. Cain LE, Logan R, Robins JM, et al. cordant couples in sub-Saharan Africa: a mission of human immunodeficiency vi- When to initiate combined antiretroviral systematic review and meta-analysis. Lan- rus type 1. N Engl J Med 2000;342:921-9. therapy to reduce mortality and AIDS- cet Infect Dis 2010;10:770-7. 7. Baeten JM, Kahle E, Lingappa JR, et defining illness in HIV-infected persons 30. Celum C, Wald A, Lingappa JR, et al. al. Genital HIV-1 RNA predicts risk of in developed countries: an observational Acyclovir and transmission of HIV-1 from heterosexual HIV-1 transmission. Sci study. Ann Intern Med 2011;154:509-15. persons infected with HIV-1 and HSV-2. Transl Med 2011;3:77ra29. 19. Eshleman SH, Hudelson SE, Redd AD, N Engl J Med 2010;362:427-39. 8. Bunnell R, Ekwaru JP, Solberg P, et al. et al. Analysis of genetic linkage of HIV 31. Lowrance D, Makombe S, Harries A, Changes in sexual behavior and risk of from couples enrolled in the HIV Preven- et al. Lower early mortality rates among HIV transmission after antiretroviral ther- tion Trials Network 052 trial. J Infect Dis patients receiving antiretroviral treatment apy and prevention interventions in rural (in press). at clinics offering cotrimoxazole prophy- Uganda. AIDS 2006;20:85-92. 20. DeMets DL, Lan KK. Interim analysis: laxis in Malawi. J Acquir Immune Defic 9. Donnell D, Baeten JM, Kiarie J, et al. the alpha spending function approach. Syndr 2007;46:56-61. Heterosexual HIV-1 transmission after Stat Med 1994;13:1341-52. 32. Cohen MS, Gay C, Kashuba AD, Blower initiation of antiretroviral therapy: a pro- 21. O’Brien PC, Fleming TR. A multiple S, Paxton L. Narrative review: antiretrovi- spective cohort analysis. Lancet 2010;375: testing procedure for clinical trials. Bio- ral therapy to prevent the sexual trans- 2092-8. metrics 1979;35:549-56. mission of HIV-1. Ann Intern Med 2007; 10. Del Romero J, Castilla J, Hernando V, 22. Dyer JR, Kazembe P, Vernazza PL, et 146:591-601. Rodriguez C, Garcia S. Combined antiret- al. High levels of human immunodefi- 33. Dieffenbach CW, Fauci AS. Universal roviral treatment and heterosexual trans- ciency virus type 1 in blood and semen of voluntary testing and treatment for pre- mission of HIV-1: cross sectional and pro- seropositive men in sub-Saharan Africa. vention of HIV transmission. JAMA 2009; spective cohort study. BMJ 2010;340:c2205. J Infect Dis 1998;177:1742-6. 301:2380-2. 11. Reynolds SJ, Makumbi F, Nakigozi G, 23. Novitsky V, Ndung’u T, Wang R, et al. 34. Burns DN, Dieffenbach CW, Vermund et al. HIV-1 transmission among HIV-1 Extended high viremics: a substantial frac- SH. Rethinking prevention of HIV type 1 discordant couples before and after the tion of individuals maintain high plasma infection. Clin Infect Dis 2010;51:725-31. introduction of antiretroviral therapy. viral RNA levels after acute HIV-1 subtype [Erratum, Clin Infect Dis 2010;51:995.] AIDS 2011;25:473-7. C infection. AIDS 2011 April 18 (Epub 35. Smith K, Powers KA, Kashuba AD, 12. Granich RM, Gilks CF, Dye C, De ahead of print). Cohen MS. HIV-1 treatment as prevention: Cock KM, Williams BG. Universal volun- 24. Ping L-H, Nelson J, Hoffman I, et al. the good, the bad, and the challenges. tary HIV testing with immediate antiret- Characterization of V3 sequence hetero- Curr Opin HIV AIDS 2011;6:315-25. roviral therapy as a strategy for elimina- geneity in subtype C human immunodefi- Copyright © 2011 Massachusetts Medical Society. tion of HIV transmission: a mathematical ciency virus type 1 isolates from Malawi: model. Lancet 2009;373:48-57. underrepresentation of X4 variants. J Virol 13. Das M, Chu PL, Santos GM, et al. De- 1999;73:6271-81. creases in community viral load are ac- 25. Wawer MJ, Gray RH, Sewankambo 10.1056/nejmoa1105243 nejm.org 13 editorial EMBARGOED UNTIL 2:00 PM US ET THURSDAY, 22 DECEMBER 2011 Science Breakthroughs As announced in this issue, Science’s choice for Breakthrough of the Year for 2011 Bruce Alberts is Editor- is based on the paper Prevention of HIV-1 Infection with Early Antiretroviral Therapy* (see in-Chief of Science. p. XXXX). This provocative choice was made after much deliberation involving our News and Editorial staff, plus our Board of Reviewing Editors. The study involved more than 1700 heterosexual couples, of whom one partner was infected with the human immunodeficiency virus (HIV) and the other was not at the start of the trial. All those infected still had relatively intact immune systems. The study gave antiretroviral drugs to half of the infected people and delayed giving treatment to the other half until their immune systems declined to a danger- ous degree. The results of this early treatment with a cocktail of antiviral drugs were dra- matic, lowering the rate at which the HIV-free partner became infected 20-fold, while also improving outcomes for the infected partner. In combination with other promising clinical trials, the results have galvanized efforts to end the world’s AIDS epi- demic in a way that would been inconceivable even a year ago. "The goal of an AIDS-free generation is ambitious, but it is possible," U.S. Secretary of State Hillary Clinton told scientists last month. This is not to say that we can abandon the search for an AIDS vaccine. Nor will profound change come overnight from the prom- ise of using treatment as prevention. But for its role in making suc- cess conceivable, we have chosen the results of this trial as our Breakthrough of the Year. Picking the nine Runners-Up was unusually challenging this year. In most fields, there was good steady progress, which is how science normally works. My favorite runner-up is the successful outcome from the heroic, problem-plagued Japanese mission to the Itokawa asteroid. The illuminating analysis of the asteroid dust returned by the Hayabusa spacecraft provided that nation with a tri- umph to help balance the year’s greatest tragedy: the huge earthquake and tsunami that struck northern Japan in March 2011. Already there are signs that 2012 will be an exciting science year. This month, physi- cists at the European particle physics laboratory CERN may have seen signs of the elusive Higgs boson, the hypothetical fundamental particle that would explain how other particles obtain their mass. This discovery would be one of the biggest breakthroughs in science, and we await the outcome of the latest reported glimpses. But predicting the future of science is always treacherous, and perhaps the greatest pleasure for those of us at Science is the cer- tainty that there will be amazing surprises in the year ahead. Not all of the news for science has been good this year. Regrettably, we live in an age where “science denial” has become fashionable. For instance, in the United States, the pres- sure to conform has become so great that even many politicians who know better have become unwilling to speak out to support what science knows about climate change. Part of the reason is that politicians need to raise funds to compete effectively in elections, and the large amount of money spent by special interest groups distorts the public debate. To counter such science denial, I have repeatedly argued on this page that scientists need to pay much more attention to science education. Teaching is not the same as simply telling students what one knows—a common approach pursued through lecturing. Instead, the scientific community needs to strongly support evidence-based methods for improving how students learn science both in college and at lower levels, focusing on empowering all students with the reasoning and problem-solving skills of scientists. Then, perhaps, Science might one day be able to highlight the striking results of a large “clinical trial” in science education as ) t our Breakthrough of the Year, reporting the clear benefits to students inspired by a carefully gh designed, hands-on, inquiry-based exploration of the world. – Bruce Alberts ri op); ( op); 10.1126/science.1217831 t *M. S. Cohen et al., N. Engl. J. Med. 365, 493 (2011). ( CREDITs: 1604 23 DECEMBER 2011 VOL 334 SCIENCE www.sciencemag.org EMBARGOED UNTIL 2:00 PM US ET THURSDAY, 22 DECEMBER 2011 the other half delayed treatment until CD4 HIV Treatment as Prevention counts dropped below 250. The researchers planned to compare the On 1 December, George Washington Univer- the degree to which the viral load in blood pre- groups until 2015. But on 28 April, an inde- sity in Washington, D.C., hosted “The Begin- dicts the risk of HIV transmission,” they cau- pendent monitoring board that periodically ning of the End of AIDS,” a splashy World tioned. reviewed the data stunned Cohen and his AIDS Day event that featured three U.S. pres- Then in May of this year, the 052 clinical collaborators when it recommended that the idents, business magnates, and rock stars. The trial conducted by the HIV Prevention Trials results of the trial be made public as soon catalyst that brought them together was some- Network reported that ARVs reduced the risk as possible. Of the 28 people who become thing Anthony Fauci, the top U.S. government of heterosexual transmission by 96%. “Now infected with HIV that genetically matched HIV/AIDS scientist, told the crowd even we have absolute, confirmed data,” said Fauci the viruses in their long-term partners, only 1 year ago would have seemed “wishful think- at an AIDS conference this summer in Rome one was in the early treatment group—which ing”: a clinical trial dubbed HPTN 052 and its where researchers first presented the HPTN also experienced 41% fewer serious health “astounding” result. 052 data in detail. Fauci, who heads the U.S. problems associated with HIV. Infected HIV/AIDS researchers have long debated National Institute of Allergy and Infectious people in the delayed arm of the study were com ws whether antiretroviral drugs (ARVs) used to Diseases—the main funder of the $73 million offered ARVs immediately. Ne k/ treat HIV-infected people might have a dou- trial—said the challenge now was to apply the The HPTN 052 results and other recent e ble benefit and cut transmission rates. To results. “We just need to take that data and successes have raised hopes that combining some it was obvious: ARVs reduce HIV lev- run with it,” he said. “The idea of the tension such interventions can now end AIDS epidem- .; J. D. Talas D. J. .; els, so individuals should be less infectious. between treatment and prevention, we should ics in entire countries, if not the world. ARVs c Skeptics contended that this was unproven. just forget about it and just put it behind us, are not a vaccine: People must take them for In , Indeed, a consensus statement issued by the because treatment is prevention.” Because of decades, which is difficult to do and costly. imited nl Swiss Federal Commission for HIV/AIDS in HPTN 052’s profound implications for the But many call HPTN 052 a “game changer” U future response to the AIDS epi- because of its near 100% efficacy. “It has suals demic, Science has chosen it as its had an impact on our vision for the future,” i D/V S Breakthrough of the Year. says Françoise Barré-Sinoussi, a virologist C U Myron Cohen, an HIV/AIDS at the Pasteur Institute in Paris who shared CMIR, researcher at the University of the Nobel Prize for helping to discover HIV. N North Carolina, Chapel Hill, who Researchers must continue—and even inten- an, m s heads the ongoing HPTN 052 sify—efforts to develop an effective AIDS i trial, said the finding’s impact sur- vaccine and cure, Barré-Sinoussi stresses, but Ell k r prised him. “People were inter- she notes that countries can apply treatment as Ma ested in the idea of treatment as prevention today. d , an , i prevention, but it created a hurri- Julio Montaner, a prominent advocate ll cane-force wind behind the strat- of the strategy at the University of British te egy,” Cohen says. “The result was Columbia, Vancouver, in Canada says HPTN hn Gua hn so unambiguous.” 052 has persuaded leaders such as U.S. Presi- o As Cohen and colleagues dent Barack Obama—whose administration J k, tric a p explained in the 11 August New recently announced a policy goal of creating z England Journal of Medicine, “an AIDS-free generation”—to take action. it Double duty. This year a study proved that anti-HIV drugs both F n HPTN 052 enrolled 1763 “dis- “Clinicians and policymakers are always ee treat and prevent HIV infections. hl t cordant” couples in which one asking for the ultimate evidence,” Montaner a K k, 2008 that said effective ARV treatment could person at the study’s start had a known HIV says. “HPTN 052 was the unequivocal piece c virtually stop heterosexual transmission was infection. The infected partner could not be of the puzzle to close any doubts.” n denounced as “appalling,” “inconclusive and taking ARVs and had to have between 350 Given resource constraints and logistical eeri irresponsible,” “dangerous,” and “mislead- D as and 550 CD4 cells per milliliter, which indi- hurdles, treatment as prevention isn’t going to om ing.” The Joint United Nations Programme on cates that the person had some immune dam- sweep the world anytime soon. But HPTN 052 HIV/AIDS and the World Health Organiza- age but had yet to develop AIDS (defined as has made imaginations race about the what- tion also responded with alarm, urging people fewer than 200 CD4s). Five countries in sub- ifs like never before, spotlighting the scientif- to continue using condoms and stressing that Saharan Africa participated, as did Brazil, ically probable rather than the possible. And semen or vaginal secretions might harbor the India, Thailand, and the United States. The now a growing number of HIV/AIDS experts virus even when blood tests showed no trace study randomly assigned half the infected are insisting that the irresponsible and appall- of it. “More research is needed to determine people to start ARVs immediately, while ing thing to do is nothing. –Jon Cohen Th BOTTOM): TO (TOP CREDITs 1628 23 december 2011 VOL 334 SCIENCE www.sciencemag.org PolicyForum EMBARGOED UNTIL 2:00 PM US ET THURSDAY, 22 DECEMBER 2011 HIV/AIDS Antiretrovirals face formidable obstacles ARVs as HIV Prevention: for wide-scale prevention of HIV infection. A Tough Road to Wide Impact James D. Shelton1* ompelling new evidence showing that increases the testing burden. Male circumcision 1% oral antiretroviral drugs (ARVs) can Even an exceptionally opti- Behavior changes 3% prevent heterosexual HIV transmis- mistic model (that assumed C Mother-to-child sion has recently burst upon us. The HPTN universal testing every year, transmission 13% 052 randomized study confirmed earlier nearly complete adherence, observational data that, if the HIV-positive and 40% of impact from other partner in a discordant couple took ARVs, prevention programming) pro- Condom 6% transmission to the HIV-negative partner was jected it would take a decade virtually eliminated, at least for more than 2 to bring new infections in gen- Sex work 3% years (1). Two randomized studies found that eralized epidemics (where the taking ARVs by the HIV-negative partner in a epidemic affects a substantial Men having sex with men 4% discordant couple (preexposure prophylaxis portion of the general popula- or PrEP) also reduced transmission substan- tion) close to zero and 50 years Intravenous drug use 7% tially (2). These results have ignited enthu- for virtual infection elimina- siasm for ARVs as a breakthrough for HIV tion (7). Treatment and related 63% prevention. Indeed, Joint United Nations For oral PrEP, the reservoir Global HIV program funding 2011 [Derived from (19)]. Costs do Programme on HIV/AIDS (UNAIDS) Exec- of uninfected people is far too not include general support and research. utive Director Michel Sidebe has described it large. Rather, the challenge as “game changing” (3). is identifying those potentially at substantial side effects (10). Adherence among symp- Are ARVs a magic bullet to stop the global risk for HIV acquisition. For some, that may tom-free people is even more problematic, epidemic in its tracks? It is not that simple. be relatively straightforward, such as identi- especially if they experience side effects. First, two additional trials of oral PrEP failed fied negative partners in a discordant couple, These issues are greater for an HIV-unin- to show an impact (4). Moreover, such tri- but beyond those the potential for PrEP is fected person, who might choose PrEP, as als are conducted under optimal conditions unclear—even for some at higher risk, such as ARVs have no clinical benefit. Poor adherence designed both to maximize proper use of those with multiple sexual partners. was apparently a major reason for failure to ARVs and to reduce risky behavior. Achieving Missing very early infections. Within the show impact in two recent oral PrEP trials (4), an impact of ARVs at the population level is first weeks of infection, people are much although low levels of ARV in the female gen- quite another matter. HIV is an elusive enemy, more contagious than in the multiyear ital tract after oral administration may have and a variety of major logistical, cost, bio- chronic phase, because of both the higher also limited efficacy 11( ). logic, and behavior impediments stand in the viremia and the nature of early transmitted Drug resistance. ARV-resistance muta- way of broad impact at scale. virus (8). This early infectiousness allows tions already are found in untreated patients. Identifying infected and uninfected at for chains and clusters of rapid transmis- Providing ARVs on a more massive scale for high risk. There are an estimated 34 million sions crucial to propagation of the epidemic many years opens the door to more resistance, infected people globally of whom some 6.6 (9). Such infections account for very roughly especially when use would be long and adher- million are already taking ARVs. But 2.7 mil- one-third of transmission events in general- ence possibly lower. Evidence from Africa lion become infected each year (5). Simply ized epidemics, depending on the maturity of indicates the proportion of ARV recipients identifying and reaching a major proportion the epidemic, but they can propagate rapidly with resistance mutations has increased each of the infected but untreated (and frequently and spawn subsequent generations of onward year since ARV roll-out (12). Resistance has unaware) people is a Herculean task. Many transmissions. But most current HIV tests do been observed with PrEP apparently early people are difficult to reach and/or resistant not detect acute infections (8). Even with during infection (13). to testing. For example, Lesotho, a relatively more sensitive tests, the interval of maximal Risk compensation. The concept that belief advanced compact country with the world’s infectiousness is so narrow, and HIV inci- in the protective powers of ARVs could lead third highest HIV prevalence, launched a dence so relatively low, that few people are to more risky behavior is a major concern. national campaign in 2004 to test everyone. tested during this critical time. Promotion of condoms in a community inter- Yet by 2009, only just over half of the adult Acceptance and long-term adherence. vention in Uganda resulted in increased risky population had been tested even once (6). And For ARVs as prevention to have a substan- behavior compared with that of the control the perpetual stream of newly infected people tial impact, very large numbers of those per- population (14). Riskier sexual behavior has sons testing positive—most symptom-free— increased in the large Amsterdam cohort of would need to take them voluntarily and con- men who have sex with men (MSM) from 1Bureau for Global Health, Washington, DC 20523, USA. E-mail: [email protected] sistently for a lifetime. Even now, adherence 1996 onward (15). Evidence from a Swiss *The views expressed are not necessarily those of U.S. is far from perfect, and some patients discon- cohort indicates increased risky sex among Agency for International Development. tinue for a variety of reasons, including drug those taking ARVs who are informed of www.sciencemag.org SCIENCE VOL 334 23 december 2011 1645 policyforum EMBARGOED UNTIL 2:00 PM US ET THURSDAY, 22 DECEMBER 2011 ARVs’ prevention benefit 16( ). These findings care, and achieve durable viral suppression ing underfunding (see the chart), especially argue for not relying only on ARVs but also has been difficult in the United States (23). the core prevention approaches—behavior reinforcing complementary behavioral risk Financing is also a problem in providing ARV change, male circumcision, and condoms. reduction, as occurred in each successful clin- assistance for U.S. low-income patients who Nevertheless, current prevention interven- ical trial. For PrEP, a particular worry is that meet current treatment guidelines (24). tions are beginning to take hold. HIV inci- some individuals would take ARVs sporadi- Some reports have suggested an impact of dence is declining globally (5) albeit slowly. cally and then engage in risky sex. ongoing ARV treatment programs on reduc- Remarkable declines in incidence related to Drug toxicity. For those with advanced ing incidence of HIV in urban populations, reduced risky behavior have occurred in key HIV, the benefit of ARVs far outweighs the e.g., MSM in San Francisco (25) and IDUs African countries (33). Accordingly, ARVs as risks, and HPTN 052 found some clinical ben- in British Columbia (26). However, these are prevention must not jeopardize already pre- efit to individuals in earlier stages. Still, ARVs imprecise observational analyses that follow cariously low funding for complementary pre- have toxicity that becomes an even more new diagnoses rather than true incidence and vention interventions, particularly the behav- important concern for those who are HIV- are subject to important confounders (27). ioral ones. Likewise, research to develop HIV negative. For example, tenofovir, an ARV Conversely, HIV diagnosis has increased in vaccines must remain a priority. ARVs are no included in all prevention trials to date, may settings of MSM in Canada and Australia “magic bullet.” But ARVs’ best potential is to cause kidney injury (17). Further, nucleoside (28) and incidence in an intensive cohort in contribute to the existing combination arsenal, reverse transcription inhibitors induce accel- Amsterdam (15), despite widespread ARVs. which, well applied, can have a major impact erated mitochondrial DNA mutations that HIV incidence in the United States has in stemming the global HIV pandemic. might result in premature aging and eventual remained constant since the introduction of multiorgan disease (18). ARVs (29). References and Notes Cost and human resources. Even with Conclusion. Oral ARVs definitely have a 1. M. S. Cohen et al., N. Engl. J. Med. 365, 493 (2011). 2. J. Cohen, Science 333, 393 (2011). massive funding, many programs are chal- supporting role to play in prevention as part 3. UNAIDS, AIDS at 30: Nations at the Crossroads (UNAIDS, lenged to meet current ongoing costs for of a combination approach based on every Geneva, 2011); www.unaids.org/unaids_resources/ treatment. Recent global estimates indicate tool we can muster. Such tools include male aidsat30/aids-at-30.pdf. 4. J. Cohen, ScienceInsider 28 September 2011; http://news. nearly two-thirds of the $7.0 billion current circumcision, condoms, partner limitation, sciencemag.org/scienceinsider/2011/09/a-dizzying-second- basic program funding supports treatment- behavior change, and needle exchange work- twist-in-trial.html. and care-related services (see the chart, page ing in synergy (19). But we need to proceed 5. UNAIDS, World AIDS Day Report (UNAIDS, Geneva, 2011); www.unaids.org/en/media/unaids/contentassets/ 1645) (19), even though less than half of treat- selectively and incrementally and to gather documents/unaidspublication/2011/JC2216_WorldAIDS- ment-eligible people are receiving ARVs. In more evidence. Priority for treatment should day_report_2011_en.pdf. a world currently beset with economic stress be given to those with advanced disease who 6. Lesotho Ministry of Health and Social Welfare, Lesotho and with increasing emphasis on other com- are as yet untreated. They would benefit clini- Demographic and Health Survey 2009 (Ministry of Health and Social Welfare, Maseru, Lesotho, and ICF Macro, Cal- pelling global health priorities, the prospect cally and provide greater prevention impact verton, MD, 2010); www.measuredhs.com/pubs/pdf/FR241/ of increasing provision of ARVs several- because their lower CD4 counts and higher FR241.pdf. fold seems unrealistic. Furthermore, the cost viral load make them substantially more 7. R. M. Granich et al., Lancet 373, 48 (2009). 8. M. S. Cohen et al., N. Engl. J. Med. 364, 1943 (2011). would be cumulative, as survival improves likely to transmit infection (30). Some mod- 9. S. M. Goodreau et al., AIDS Behav. 30 December 2010, and progressively more people take ARVs eling suggests high levels of ARV coverage 10.1007/s10461-010-9858-x. for treatment and prevention. Although some in a few key countries may be reducing trans- 10. R. P. Dalal et al., J. Acquir. Immune Defic. Syndr. 47, 101 economies of scale could accrue, identifying mission (5). Other priorities include individu- (2008). 11. K. B. Patterson et al., Sci. Transl. Med. 3, 112re4 (2011). HIV-infected people who are the most diffi- als more likely to transmit HIV, such as sex 12. R. L. Hamers et al., Lancet Infect. Dis. 11, 750 (2011). cult to find would likely increase marginal workers, and a partner in an identified discor- 13. C. B. Hurt, J. J. Evon Jr., M. S. Cohen, Clin. Infect, Dis. costs and further stress frail health systems. dant couple regardless of CD4 count. Women 53, 1265 (2011). 14. P. Kajubi et al., J. Acquir. Immune Defic. Syndr. 40, 77 Concentrated epidemics. Although gener- identified during pregnancy who successfully (2005). alized HIV epidemics represent most of the take ARVs to prevent vertical transmission 15. I. A. V. Jansen et al., AIDS 25, 493 (2011). global burden, ARVs also have potential for could also be a priority. These priorities align 16. B. Hasse et al., Clin. Infect. Dis. 51, 1314 (2010). 17. B. Fernandez-Fernandez et al., Aids Res. Treat. 2011, 1 situations where HIV largely affects MSM with a recent President’s Emergency Plan for (2011). and to a lesser degree injecting drug users AIDS Relief (PEPFAR) advisory (31). At the 18. B. A. I. Payne et al., Nat. Genet. 43, 806 (2011). (IDUs). This is the case in the United States, same time, we need to strengthen behavioral 19. B. Schwartländer et al., Lancet 377, 2031 (2011). where infection rates are lower and resources risk reduction and adherence for these high- 20. G. A. Millett et al., J. Acquir. Immune Defic. Syndr. 55, (suppl. 2), S144 (2010). are much greater. About four-fifths of those priority individuals to avoid compromising 21. B. G. Brenner et al., AIDS 22, 2509 (2008). living with HIV in the United States have had ARV’s prevention benefit. 22. R. M. Grant et al., N. Engl. J. Med. 363, 2587 (2010). at least one HIV test (20), but service delivery We do not know the extent to which find- 23. E. M. Gardner et al., Clin. Infect. Dis. 52, 793 (2011). 24. R. Trubo, JAMA 306, 253 (2011). to these populations can be difficult. Missing ings in small-scale trials will extend to large- 25. M. Das et al., PLoS one 5, e11068 (2010). acute infection is definitely a problem; some scale implementation. Some 50 studies on 26. J. S. Montaner et al., Lancet 376, 532 (2010). viral genetic-linkage evidence from Canada ARVs as prevention are under discussion 27. J. D. Shelton et al., Lancet 376, 1824, (2010). suggests a substantial proportion of transmis- (32), of which at least four are in larger study 28. A. E. Grulich, D. P. Wilson, Lancet 376, 1824 (2010). 29. J. Prejean et al., PLoS ONE 6, e17502 (2011). sion among MSM may result from serial acute populations. Such research should inform any 30. D. Donnell et al., Lancet 375, 2092 (2010). infections (21). A study of PrEP in MSM in major expansion of ARVs as prevention. We 31. PEPFAR, 2011, www.pepfar.gov/documents/organization/ the United States and South America found also need better, cheaper, longer-acting, more 177126.pdf. 32. R. Granich et al., Curr. HIV Res. 9, 446 (2011). an efficacy of only 44%, at least partly attrib- user-friendly, and program-friendly ARVs for 33. D. T. Halperin et al., PLoS Med. 8, e1000414 (2011). utable to poor adherence (22). The ability to treatment and prevention. identify HIV-positive people, link them to Primary prevention suffers from strik- 10.1126/science.1212353 1646 23 december 2011 VOL 334 SCIENCE www.sciencemag.org HIV study named 2011 Breakthrough of the Year by Science NIH-funded treatment-as-prevention study heralded as a major advance The journal Science has chosen the HPTN 052 clinical trial, an international HIV prevention trial sponsored by the National Institute of Allergy and Infectious Diseases (NIAID), part of the National Institutes of Health, as the 2011 Breakthrough of the Year. The study found that if HIV- infected heterosexual individuals begin taking antiretroviral medicines when their immune systems are relatively healthy as opposed to delaying therapy until the disease has advanced, they are 96 percent less likely to transmit the virus to their uninfected partners. Findings from the trial, first announced in May, were published in the New England Journal of Medicine in August. The complete top 10 list of 2011 scientific breakthroughs appears in the Dec. 23, 2011 issue of Science. "The HPTN 052 study convincingly demonstrated that antiretroviral medications can not only treat but also prevent the transmission of HIV infection among heterosexual individuals," said NIAID Director Anthony S. Fauci, M.D. "We are pleased that Science recognized the extraordinary public health significance of these study results. This recognition also is a credit to the hard work and dedication of the HPTN 052 researchers and the more than 3,000 study participants who selflessly gave their time and energy to make such a significant contribution to the fight against HIV/AIDS." Led by study chair Myron Cohen, M.D., director of the Institute for Global Health and Infectious Diseases at the University of North Carolina at Chapel Hill, HPTN 052 began in 2005 and enrolled 1,763 heterosexual couples in Botswana, Brazil, India, Kenya, Malawi, South Africa, Thailand, the United States and Zimbabwe. Each couple included one partner with HIV infection. The investigators randomly assigned each couple to either one of two study groups. In the first group, the HIV-infected partner immediately began taking a combination of three antiretroviral drugs. The participants infected with HIV were extensively counseled on the need to consistently take the medications as directed. Outstanding compliance resulted in the nearly complete suppression of HIV in the blood (viral load) of the treated study participants in group one. In the second group (the deferred group), the HIV-infected partners began antiretroviral therapy when their CD4+ T-cell levels — a key measure of immune system health — fell below 250 cells per cubic millimeter or an AIDS-related event occurred. The HIV-infected participants also were counseled on the need to strictly adhere to the treatment regimen. The study was slated to end in 2015, but an interim data review in May by an independent data and safety monitoring board (DSMB) found that of the total 28 cases of HIV infection among the previously uninfected partners, only one case occurred among those couples where the HIV- infected partner began immediate antiretroviral therapy. The DSMB, therefore, called for immediate public release of the study's findings. The magnitude of protection against HIV infection demonstrated in HPTN 052 has made the successful strategy of the clinical trial a key component of public health policies recently discussed by federal officials and others saying that achieving an end to the HIV/AIDS pandemic is now feasible with additional research and implementation efforts. "On its own, treatment as prevention is not going to solve the global HIV/AIDS problem," said Dr. Fauci. "Yet when used in combination with other HIV prevention methods — such as knowing one's HIV status through routine testing, proper and consistent condom use, behavioral modification, needle and syringe exchange programs for injection drug users, voluntary, medically supervised adult male circumcision, preventing mother-to-child transmission, and, under some circumstances, antiretroviral use among HIV-negative individuals — we now have a remarkable collection of public health tools that can make a significant impact on the HIV/AIDS pandemic." "Scale-up of these proven prevention methods combined with continued research toward a preventive HIV vaccine and female-controlled HIV prevention tools places us on a path to achieving something previously unimaginable: an AIDS-free generation," Dr. Fauci added. HPTN 052 was conducted by the HIV Prevention Trials Network, which is largely funded by NIAID with additional funding from the National Institute on Drug Abuse and the National Institute of Mental Health, both part of the NIH. Source: http://www.nih.gov/news/health/dec2011/niaid-22.htm The University of North Carolina at Chapel Hill Appendix A EXECUTIVE SUMMARY Board of Trustees January 17, 2012 Effective No. College/Division Name Dept./School Current Rank New Rank Date Salary Personnel Actions New Appointments without Tenure 1 Academic Affairs Christopher Clark II Political Science Lecturer Assistant Professor 7/1/2012 $92,500 2 Health Affairs Joseph Tucker Medicine N/A Assistant Professor 2/1/2012 $105,000 Promotion to Full Professor 1 Health Affairs Susan Blalock Pharmacy Assistant Professor Professor 1/27/2012 $120,868 Reappointments to the Same Rank 1 Academic Affairs Sreekalyani Shankar Statistics & Operations Research Assistant Professor Assistant Professor 7/1/2013 $75,000 Bhamidi 2 Academic Affairs Xi Chen Political Science Assistant Professor Assistant Professor 7/1/2013 $73,000 Actions Conferring Tenure Promotion Conferring Tenure 1 Health Affairs Kristin Reiter Health Policy & Management Assistant Professor Associate Professor 7/1/2012 $107,870 Reappointment Conferring Tenure 1 Health Affairs William Zamboni Pharmacy Associate Professor w/o Tenure Associate Professor w/Tenure 1/27/2012 $120,000 New Appointments Conferring Tenure 1 Health Affairs Denise Rhoney-Metzger Pharmacy N/A Associate Professor w/Tenure 1/27/2012 $144,000 Designation/Reappointments to Distinguished Professorships 1 Health Affairs Mary Palmer Nursing Helen W. & Thomas L. Umphlet Helen W. & Thomas L. Umphlet 1/1/2012 - $103,291 Distinguished Professor Distinguished Professor 12/31/2021 2 Health Affairs Anthony Viera Family Medicine Associate Professor Charles Bayne Wilkerson, MD '06 2/24/2012 - $126,100 Associate Term Professor 2/23/2016 10 Total Page 1