JOINT CLINICAL RESEARCH CENTRE (JCRC) 2016 Annual Report

JOINT CLINICAL RESEARCH CENTRE (JCRC)

2016 Annual Report

For Quality Health Care Services

Table of Contents

List of Acronymns……………………………………………………………………………..iii JCRC Patron ……………………………………………………………………………………iv JCRC Board Management structure……………………………………………………………v JCRC Senior Management structure……………………………………………………………vi Message from the JCRC Executive Director……………………………………………………ix Brief about JCRC………………………………………………………………………………..x

JCRC Silver Jubilee Celebrations …………………………………………..………………1

Clinical Care services……………………………………………………………..……………5 Nursing……….…………………………………………………………..……………..6 Paediatric Clinic …………………………………………………………...…………...9 Private Clinic……………………………………………………………..…………….10 Laboratory Services……………………………………………………….…….…………….13 CWRU Collaborative Laboratory…………………………………………………...…14 Tuberculosis Laboratory………………………………………………….……………15 Research Services…………………………………………………………………………...…16 ACTG…………………………………………………………………………….…….22 Finance and Administration………….…………………………………………………...... 24 ICT…………………………………………………………….…………………….….24 Finance….………………………………………………………..…………….……….25 Human Resources………………………………………………………………………26 Stores………………………………………………………………..…..………………27 Projects…………………………………………………………………………….……………28 THALAS………………………………………………………………………………..28 ESP……………………………………………………………………………………..31 RCE ……..…………………………………………………………………………………...... 35 Pictorial representation of the JCRC Silver Jubilee………………………………..……….37 Staff Accomplishments of the year…………………………………………………………....43 RCE Contacts…………………………………………………………………………..………55

List of Acronyms

EMTCT Elimination of Mother to Child Transmission

RCE Regional Centre of Excellence

ANC Anti natal care

PLHIV People Living with HIV/AIDS

TB Tuberculosis

UNCHE Uganda National Council of Higher Education

WHO World Health Organisation

ICEA Integrated Clinical Enterprises Application

LIMS Laboratory Information Management System

SCIPHA Strengthening Civil Society for Improved HIV/AIDS and OVC service delivery

PEP Post Exposure Prophylaxis

FP Family Planning

USAID United States Agency for International Development

THALAS Targeted HIV/AIDS and Laboratory Sevices

MOH Ministry of Health

CWRU Case Western Reserve University

CAP College of American Pathology

IPs Implementing Partners

OVC Orphans and Vulnerable Children

IDI Infectious Disease Institute

MUJHU Makerere University Johns Hopkins University

DSDM Disseminated Service Delivery Model

GCLP Good Clinical & Laboratory Practice

CAB Community Advisory Board

iii

JCRC PATRON

H.E. Yoweri Kaguta Museveni

JCRC Board Management Structure

Board Chairman: Prof. J. Epelu Opio

Prof. Peter .N. Mugyenyi Mr. Ben Okello Prof. Nelson Dr. Jesse Kagimba (Executive Director –JCRC) Luwum Ssewankambo

Hon. Ruth Jane Dr. James Makumbi Dr. Jessica Jita Mr. Richard Masereje Aceng (Board Secretary)

Prof. Manfred Dietrich Dr. Cissy Kityo (External Advisor) (ex-official)

JCRC Senior Management Team

Prof. Peter N. Mugyenyi FRCP ScD Executive Director JCRC

Dr. Cissy Kityo Deputy Executive Director

Dr. Francis Ssali Dr. Victor Musiime. Benson Ouma Director Clinical Incharge Directorate of Research Director Laboratory

Dr. Henry Mugerwa Dr. William Tamale Dr. Iva Natukunda Sr. Deborah Masiira Head of Research Clinic Manager Head Pediatrics Head Nursing & Deputy Incharge Research Directorate

Rose Byaruhanga Paul Ocitti Head Counseling Head Pharmacy

Ameria Natukunda Collins Makanga Fred Byaruhanga Godfrey Kuboi Head HRM Finance Manager Business Dev’t Manager Chief Programmer

Nsumba Lameck Annet Namara Nelson Kakande Boaz Wakabi Internal Auditor Head Stores Training Quality Head Procurement Assurance Specialist

vii

JCRC Regional Heads

Dr. Abbas Lugemwa Dr.James Abach Dr. Allan Musinguzi Dr. Keith Baleta Faith Balmoi Head Mbarara Head Gulu Head F/Portal RCE Head Mbale Head Kakira

Project Heads

Michael Kabugo Denis Akakimpa THALAS C.O.P ESP Project Manager

James Rusoke Alfred Tumwesigye Incharge Estates Head Transport

viii

Message from the Executive Director

I start by paying tribute to our patron H.E. Yoweri K. Museveni, the JCRC Board of trustees, our partners and all staff upon attaining 25 years of quality medical research, training and health care which was commemorated on 11th November, 2016.

Collaborative networks continue to enhance research activities at JCRC with 14 studies successfully concluded in 2016, 15 presentations made at international conferences such as CROI and IAS, and 33 peer reviewed publications made in 2016.

The laboratory capacity has been advanced with the completion of the Bio-safety Level III(BSL-3) facility at JCRC Lubowa. In addition, the centre is in the final stages of CAP accreditation expected to be completed in 2017.

The center continues to maintain the highest quality standards in HIV/AIDS care and treatment services in the country with total of 15,643 patients receiving at least a clinical assessment (WHO staging) OR CD4 count OR viral load, By the end of the year, 15,402 patients were active on antiretroviral treatment, and 7.1% of these were children. The reduction in number of children newly enrolled in care is evidence to the successful implementation of Option B+ for elimination of mother to child transmission of HIV program at the clinic. As evidence of quality service delivery, one of JCRC clinic staff Ms. Florence Kintu was among the 5 candidates in the country that were recognized by USAID Uganda for her exceptional contribution towards patient care and treatment.

As a way of JCRC staying afloat, the centre strengthened sustainability strategies that include strengthening provision of private clinical services at Lubowa with capacity to provide services such as; Consultations, Ultra sound, X-rays, Dental services, Non-communicable diseases, Rheumatic heart diseases, Diabetic services, admission services and pharmaceutical services strengthened.

Once again, I congratulate the JCRC staff, the management team, the board of trustees and above all our patron H.E Yoweri K.Museveni for a successful year of implementation.

Yours Sincerely,

……………………………. Prof. Peter .N. Mugyenyi Executive Director – JCRC

Brief about JCRC

The Joint Clinical Research Centre (JCRC) is an autonomous Organization established in 1991 as a limited liability not-for-profit company. It is a joint-venture between the Uganda Ministries of Health (MoH), Ministry of Defense and Makerere College of Health Sciences. The Centre was established in 1991 to respond and provide a scientific approach to the national HIV&AIDS crisis. Over the years, various institutions and organizations such as USAID, WHO, Case Western Reserve University (CWRU), FHI, NIH, European and Developing Countries Clinical Trials Partnership (EDCTP), Medical Research Council (MRC), have partnered with JCRC for medical Research Grants to study HIV, tuberculosis (TB), malaria and other tropical diseases. JCRC also competitively wins and implements HIV/AIDS projects and was the first recipient of PEPFAR funding in December 2013 for ART scale up across Uganda under the TREAT program. Between the period December 2003 to June 2010, JCRC established 52 ART sites and 25 outreaches across the country and became the largest provider of ART in Africa before transitioning these sites to MOH for mainstreaming into the national HIV/care network. A follow on 5 year project (THALAS) which has had 2 year extension was awarded. JCRC also implemented a community project across 19 districts of Uganda (SCIPHA) increasing the mobilization towards increased HIV/AIDS treatment in the country.

Current JCRC Network Coverage: JCRC headquarters are located at Lubowa Complex, off Entebbe Road, Wakiso district, with a regional network of 6 Regional Centres of Excellence (RCEs) strategically located at Kakira, Mbale, Gulu, Fort Portal, Mbarara, and Kabale.

Vision A vibrant self sustaining centre of excellence in medical research, training and health care services

Mission To conduct quality medical research and training, provide equitable and sustainable HIV/AIDS care and other health care services in Uganda and other parts of Africa

Core Values: Integrity, Confidentiality, Compassion, Mutual Respect, Teamwork, Accountability, Continuous Learning and Excellence

JCRC JUBILEE YEAR, 2016

The Joint Clinical Research Centre (JCRC) celebrated Silver Jubilee on 11th November, 2016 marking 25 years of existence since her inception in 1991. A remarkable achievement that saw JCRC take a lead in the fight against HIV/AIDS in Uganda and sub Saharan Africa, participating in ground breaking studies which have over the years informed national and international HIV/AIDS treatment guidelines and policies.

The function was held at the new JCRC Lubowa campus on plot 101 off Entebbe Road and was graced by Rt.Hon. Ruhakana Rugunda who represented the JCRC Patron and President of Uganda H.E Yoweri K. Museveni.

The Chief Guest Rt. Hon. Dr. Ruhakana Rugunda (second right) being ushered in by the JCRC Chairman Prof. Peter Epelu (extreme right) Prof. Peter Mugyenyi (Second left) and Prof. Dr. Mbonye (left)

Rt. Hon. Dr. Ruhakana Rugunda plants a tree during the celebrations. Rt. Hon. Dr. Ruhakana Rugunda plants a tree during the celebrations.

The JCRC Board Chairman Prof. Opio Epelu (second left) Introduces some of the board members present.

The JCRC Executive Director (Prof. Peter Mugyenyi) gives his speech during the Jubilee celebrations

Rt. Hon. Dr. Ruhakana Rugunda reads the President’s speech at the function

SELECTED ACHIEVEMENTS FOR THE YEAR 2016

1. CLINICAL SERVICES

The directorate is well resourced under the leadership of the Director of Clinical Services and fully supported by professional clinicians, nurses, counselors among others that over see care and treatment of patients. Some of the services offered include; medical consultations, Ultra sound, X-rays, Dental services, non-communicable diseases including diabetic services and inpatient services.

As part of the HIV care and treatment package, the Lubowa facility enrolled 616 new patients into HIV care (4 % children < 15 years) of which 465 patients were newly initiated on ART. The clinic received 127 patients as transfer-in while already on ART. 15,643 patients received at least a clinical assessment (WHO staging) OR CD4 count OR viral load, with children below 15 years contributing 7%, a small increase from the previous year when the children accounted for 6.7%. By the end of the year, 15,402 patients were active on antiretroviral treatment, and 7.1% of these were children. The low in number of children newly enrolled in care is evidence to the successful implementation of Option B+ for elimination of mother to child transmission of HIV program at the clinic.

JCRC Staff representing the clinic team. Dr. Tamale William (third from right) is the Clinic Manager

A. Nursing;

JCRC joined the Uganda Council of Nurses and Midwives to celebrate International Nurses day by participating in the Annual Scientific Conference, with the THEME: A FORCE FOR CHANGE: IMPROVING HEALTH SYSTEMS RESILIENCE held between21st – 24th June, 2016 at Namboole stadium.

The guest of honour Hon. Dr. Joyce Moriku visiting the JCRC stall at Namboole during the Nurses Day

Participants visiting the JCRC Stall at Namboole during the Nurses day Celebrations

Among the materials displayed included; ART, Information on 1st line, 2nd line, and 3rd line treatment. Condom education and distribution was also done.

As part of celebrating the Silver Jubilee November 2016, JCRC provided free counseling and testing services to the Kampala residents at the Railway grounds, Kampala where three hundred and thirty four (334) people received free counseling and testing services during the community day and Eight (8) tested HIV positive. Those found positive were referred to the HIV clinic at Lubowa and other nearby centres of their convenience, followed up and all have been initiated in care.

The JCRC mobile laboratory phlebotomy, sample preparation, rapid HIV testing.

Member of the general public waiting to be tested to know their HIV status

Crafts displayed by the JCRC Community Liaison Volunteers (CLVs) at the railway grounds in Kampala during the free HIV/AIDS counseling and testing exercise to marl JCRC silver anniversary.

B. Pediatric clinic;

Due to continuing success of elimination of mother to child transmission (eMTCT) strategy countrywide, the total number of children in the paediatric clinic has continued to drop (current number 1126) the clinic however continues to receive children referred from other health units for specialized care especially for third line treatment and resistance testing. During the year 2016, 166 new children weretransfered to the adult clinic.

The clinic has a largely adolescent population and young adults with over 65% above the age of 12 years. Throughout this year the clinic actively initiated treatment for naïve children irrespective of age onto ART according to national and international guidelines.

Nutritional supplementation was offered through the Program for Improved Nutrition (PIN) programme. Children with severe forms of wasting are uncommon because of early initiation of ART and actively tracking treatment failures.

Psychosocial support services are also routinely offered. Three peer support meetings are held annually during the school holidays. The meetings enhance adherence among the adolescents and young adults.

A Peer support meeting with Supercharger at the JCRC training room

The Mother-Baby care point has actively followed up over 200 infants registered in the clinic in the last one year; they have all undergone DNA PCR tests. So far, there is no case of lost to follow up.

Mentoring students; Last year, two students were mentored. A counselor and a post graduate student doctor who is currently looking at the Prevalence of Hepatitis B in children attending the Paediatric clinic.

c. Private Clinic;

Services offered at the private clinic include; medical consultations, Ultra sound, X-rays, Dental services, Non-communicable diseases including diabetic services and inpatient services.

i. Dental Services

A Patient being examined at the Dental clinic

Developments done at the dental clinic include among others; opening up of a reception area, partitioning acquisition of a new X-ray machine, installation of Integrated Clinical Enterprises Application (ICEA) and acquisition of dental materials and more supplies.

The newly installed Dental X-Ray machine at JCRC.

ii. Private outpatient; a. Introduced the Renal Clinic which runs every Monday. b. The Private TB and Salvage Clinics are now operational.

A nurse attending to a TB patient at JCRC Lubowa c. The clinic Integration the Disseminated Service Delivery Model where Patients are issued 6 months supply of ART to reduce patient clinic visits and clinic patient load. d. Virologically un-suppressed clients undergo resistance testing and are transitioned to 3rd line ART if indicated. e. The implementation of the Integrated Clinical Enterprises Application (ICEA) system has seen the patient waiting time at the clinic reduced from 30-60 minutes to current 10-30 minutes.

1. LABORATORY SERVICES

The JCRC network of laboratories continued to play a significant role in HIV/AIDS prevention, diagnosis and treatment monitoring, by providing timely and accurate information for use in patient management and disease surveillance. The Laboratory at JCRC supports mainly research work which is the core of JCRC business as well as providing services to non research work for clinical diagnosis for the clinic at the centre, private practitioners and other institutions with which JCRC has memorandums of understandings. The capacity of the JCRC laboratory includes the sections of Chemistry, Hematology, Immunology, TB laboratory run in collaboration with Case Western Reserve University (CWRU) and the resistance testing laboratory.

The JCRC Scientist operating the bactec MGIT 960 machine at JCRC Lubowa

Selected achievements for the laboratory;

i. The installation and operationalisation of the LIMS (Laboratory Information Management System) improved turn-around time (TAT), management of patient reports, workload as well as sample storage. The laboratory improved TAT with both clients at Lubowa and upcountry within the RCES adequately served in a timely manner. ii. As a measure of quality assurance, all tests done within the laboratory are enrolled on the PT program at Lubowa and have alternative PT programs for upcountry centres (RCES), iii. All staff were trained in GCLP while assay specific training for benche staff is ongoing. iv. All laboratory policies were reviewed and all staff trained in the implementation of these policies in line with CAP standards. v. 4 JCRC staff were trained in bio-repository management

Note: The centre is undergoing preparation for CAP certification an exercise that requires a lot of funds to complete but worthwhile given the advantages that come with CAP accreditation. This process is expected to be completed in 2017.

a. The JCRC-CWRU TB Laboratory;

This laboratory is operated jointly with Uganda-Case Western Reserve University Research Collaboration. It is a model clinical/research laboratory whose main function is to offer top level microbiology support for tuberculosis clinical trials conducted by researchers especially from Uganda, the United States and Europe. The research activities of the lab are centered on clinical trials and translational research. A small component of basic research also goes on in the lab and is expected to expand in the coming years. In addition to research work, the lab performs routine clinical mycobacteriological procedures for diagnosis and monitoring of TB treatment for study and non-study patients.

The lab is equipped with a modern Bio-safety Level III (BSL-3) facility. This allows safe manipulation of open cultures and performance of various liquid and solid medium culture techniques.

Achievements;

1. The biggest achievement was the completion of a modern certified Biosafety Level 3 (BSL-3) containment facility to international standards. Although the laboratory physically relocated to Lubowa in October 2015, the relocation program was completed in mid 2016 with performance (re)verification of all the major equipment. 2. The laboratory started providing support services for a large, multi-centre, phase 3 clinical trial study; The TBTC Study 31.

Some of the major studies the TB laboratory handled during the year under review included;

1. TBTC Study 36 - Platform for assessment of TB treatment outcomes: an observational study of individuals treated for pulmonary TB successfully completed enrolment in December 2015. Follow-up of enrolled participants is forecast to end in June 2017. 2. DMID Protocol # 13-0018: Novel CD*+ T cell diagnostics for childhood tuberculosis (ViTi study) that stared enrolling in September 2014 and is still ongoing. 3. TBTC Study 31: A Rifapentine-containing treatment shortening regimens for pulmonary tuberculosis, a randomized, open-label, controlled phase 3 clinical trial. The study started enrolling in January 2016 and to date, over 180 participants are on the study with a cumulative number of over 1,700 specimens having been analyzed in the laboratory.

4. The laboratory was also assessed and approved to provide service for two studies starting in the year 2017. These are; i. ACTG A5349 Study: A Rifapentine-containing treatment shortening regimens for pulmonary tuberculosis study which is similar in design and practice to the TBTC Study 31. ii. Screen TB Study: An evaluation of host biomarker-based point-of-care tests for targeted screening for active TB

5.. Other accomplishments for the Tb laboratory include;

1. Acquisition of a large capacity -80 Freezer in October 2016 2. Continued participation in EQA programs (INSTAND, CAP and WHO schemes) in the year 2016. 3. Personnel training; each member of staff in the laboratory attended at least one work-related workshop during the year under review. This is in addition to undertaking the College of American Pathologists (CAP) competency assessment.

2. RESEARCH SERVICES

The year 2016 was a very successful year for the Research Department where 15 conference presentations were made at international forums such as CROI (4) and IAS (11), 30 research publications made and several new studies expected to commence in 2017.

Studies that were successfully closed in 2016:

1. WAVES, Phase 3B Study to Evaluate the Safety and Efficacy of Elvitegravir/Cobicistat/Emtricitabine/ Tenofovir Disoproxil Fumarate Versus Ritonavir-Boosted Atazanavir Plus Emtricitabine/Tenofovir Disoproxil Fumarate in HIV-1 Infected, Antiretroviral Treatment-Naïve Women

2. Gilead protocol 0117, A Phase 3, Two Part Study to Evaluate the Efficacy of Tenofovir Alafenamide Versus Placebo Added to a Failing Regimen Followed by Treatment With Elvitegravir/Cobicistat/ Emtricitabine/ Tenofovir Alafenamide Plus Atazanavir in HIV-1 Positive, Antiretroviral Treatment- Experienced Adults

3. REALITY, A randomised controlled trial to investigate three methods to reduce early mortality in adults, adolescents and children aged 5 years or older starting antiretroviral therapy (ART) with severe immuno-deficiency. The three methods were: (i) increasing the potency of ART with a 12 week induction period using 4 antiretroviral drugs from 3 classes (ii) augmented prophylaxis against opportunistic/bacterial infections and helminths for 12 weeks (iii) macronutrient intervention using ready-to-use supplementary food for 12 weeks

4. HIV-1 Reservour Substudy, This was a substudy of START (Strategic Timing of Antiretroviral Treatment) The Primary objective of this Substudy was: To determine the difference between the concentration of total HIV-1 DNA in resting CD4+ T-cells between participants after 36 to 44 months of cART in participants in one of three strata of CD4+ cell counts during screening: 800, 600-799, 500-599 cells/mm3. 5. Pulmonary sub study, The purpose of this study was to find out if starting anti-retroviral therapy (ART) at CD4 above 500 (early ART group) slows the rate of decrease in lung function over time compared to waiting to start ART until the CD4+ drops below 350 (deferred ART group)

6. BREATHER, The overall aim of the BREATHER trial was to evaluate the role of Short-Cycle Therapy (SCT) in the management of HIV-infected young people who have responded well to antiretroviral therapy (ART) and to determine whether young people with chronic HIV infection undergoing Short-Cycle Therapy of five days on ART and two days off maintain the same level of viral load suppression as those on continuous therapy, over 48 weeks.

7. LABLITE, was investigating strategies to roll out HIV treatment safely and cost-effectively in real-life settings in sub-Saharan Africa. The project worked closely with ministries of Health in 3 countries in Africa (Malawi, Zimbabwe and Uganda. It aimed to inform national and international policy on how best to use the limited funds available to increase coverage of HIV treatment.

8. A5225, A Phase I/II Dose-Finding Study of High-Dose Fluconazole Treatment in AIDS-Associated Cryptococcal Meningitis (CM)

9. A5297, An Open-Label, Proof of Concept, Randomized Trial Comparing a LPV/r-Based to an nNRTI- Based Antiretroviral Therapy Regimen for Clearance of Plasmodium Falciparum Subclinical Parasitemia in HIV-infected Adults With CD4+ Counts >200 and <350 Cells/mm3

10. A5274, Reducing Early Mortality and Early Morbidity by Empiric Tuberculosis Treatment Regimens (REMEMBER)

11. A5278s. A Multicenter Trial of the (ACTG) and AIDS Malignancy Consortium (AMC 074)- drug interaction between ART and Etoposide. It is a PK Study. Enrolled all participants from study A5264

Conference presentations:

CROI 2016

1. Transmitted Drug Resistance and First-Line ART Treatment Outcomes in Ugandan Children: Cissy Kityo; Ragna S. Boerma; Kim Sigaloff; Elizabeth Kaudha; Job Calis; Victor Musiime; Tamara Sonia Boender; Henry Mugerwa; Tobias Rinke de Wit; Peter Mugyenyi1 1Joint Clinical 2. Protease Inhibitor Resistance at 2nd-line HIV Treatment Failure in Sub-Saharan Africa: Tamara Sonia Boender; Raph Hamers; Pascale Ondoa1; Maureen Wellington; Margaret Siwale; Cissy Kityo; Sulaimon Akanmu; Kishor Mandaliya; Tobias Rinke de Wit; Kim Sigaloff; for the PanAfrican Studies to Evaluate Resistance (PASER) Study Group 3. Divergent ARV Resistance at Screening for ACTG A5288 Study of 3rd-Line ART in RLS: Carole L. Wallis; Beatriz Grinsztejn; Saran Vardhanabhuti; Robert A. Salata; Peter Mugyenyi; Catherine Godfrey; Michael Hughes; Ann Collier; John W. Mellors; for the A5288 Team 4. Safety and Efficacy of E/C/F/TAF in HIV-1 Infected Treatment-Naïve Adolescents Aditya Gaur; Hilda Kizito; Rana Chakraborty; Jagmohan Batra; Pope Kosalaraksa; Wicharn Luesomboon; Yongwu Shao; Devi SenGupta; Martin S. Rhee; Erin Quirk

IAS 2016

1. Improved adherence to antiretroviral treatment observed among children whose caregivers had positive beliefs in medicine: G Abongomera,, A Cook, M Lamorde, C Chabala, V Musiime, M Thomason, V Mulenga R Colebunders C Kityo S Walker DM Gibb and on behalf of the CHAPAS-3 Trial Team

2. Enhanced infection prophylaxis reduces mortality in severely immunosuppressed HIV- infected adults and older children initiating antiretroviral therapy in Kenya, Malawi, Uganda and Zimbabwe: the REALITY trial: J Hakim, V Musiime, AJ Szubert, A Siika, J Mallewa, C Agutu, SL Pett, M Bwakura-Dangarembizi, A Lugemwa, S Kaunda, M Karoney, K Maitland, A Griffiths, C Kityo, P Mugyenyi, AJ Prendergast, AS Walker, DM Gibb, and REALITY Trial Team1 3. 12-week raltegravir-intensified quadruple therapy versus triple first-line ART reduces viral load more rapidly but does not reduce mortality in severely immunosuppressed African HIV- infected adults and older children: the REALITY trial: C Kityo, A Siika, AJ Szubert, J Mallewa, M Bwakura-Dangarembizi, S Kabahenda, S Mwaringa, SL Pett, A Griffiths, A

Lugemwa, S Wachira, G Musoro, C Rajapakse, T Etyang, J Abach, P Wavamunno, L Nyondo- Mipando, A Reid, K Nathoo, J Hakim, DM Gibb, AS Walker, and REALITY trial team

4. Effect of PI resistance mutations on viral load in patients on PI monotherapy: JA Thompson, C Kityo, AS Walker, J Hakim, A Kambugu, JJ van Oosterhout, A Siika, A Mweemba, P Van den Eede, DT Dunn, NI Paton, and for the Earnest Trial Team

5. Ethical and practical considerations in HIV drug trial closure: perspectives of researchers in Uganda S. Nalubega, C. Evans, K. Cox, H. Mugerwa

6. Experiences of HIV-infected people within their first year of leaving HIV clinical trials in Uganda: a grounded theory assessment: S. Nalubega, C. Evans, K. Cox, H. Mugerwa

7. Impact of decentralisation on ART services at community level in rural northern Uganda: results from the Lablite population surveys: G. Abongomera, S. Kiwuwa-Muyingo, P. Revill, L. Chiwaula, T. Mabugu, A. Phillips, E. Katabira, M. Muzambi, C. Gilks, A. Chan, J. Hakim, R. Colebunders, C. Kityo, J. Seeley, D.M. Gibb, D. Ford, on behalf of the Lablite Project Team

8. Beyond clinical trials: associations between antiretroviral therapy (ART) and reporting multiple medication side-effects among adolescents in South Africa: Helen Pretty Mbaziira Natukunda, H.P. Mbaziira Natukunda, L. Cluver, E. Toska, A. Yakubovich, V. Musiime, The Mzantsi Wakho Adolescent Health Team

9. Barriers to antiretroviral treatment adherence in HIV-infected long-term treated adolescents and adults in Uganda: Seth Chekata Inzaule S. Chekata Inzaule, R. Hamers, C. Kityo, T.F. Rinke de Wit, M. Roura

10. Can HIV/AIDS infrastructure be leveraged to improve rheumatic heart disease care in Uganda?: V. Musiime, E. Okello, T. Aliku, J. Rwebembera, P. Lwabi, G. Mirembe, C. Kityo, P. Mugyenyi, M. Costa, D. Simon, R. Salata, A. Webel, A. Beaton, M. Kamya, C. Longenecker

11. Transmitted Drug Resistance and First-Line ART Treatment Outcomes in Ugandan Children: Cissy Kityo; Ragna S. Boerma; Kim Sigaloff; Elizabeth Kaudha; Job Calis; Victor Musiime; Tamara Sonia Boender; Henry Mugerwa; Tobias Rinke de Wit; Peter Mugyenyi

2016 research publications;

1. Neuroscience and awareness in the dying human brain: Implications for organ donation practices. Rady MY, Verheijde JL. J Crit Care. 2016 Aug;34:121-3. doi: 10.1016/j.jcrc.2016.04.016. Epub 2016 Apr 26.

2. Acceptability of lopinavir/r pellets (minitabs), tablets and syrups in HIV-infected children. Kekitiinwa A, Musiime V, Thomason MJ, Mirembe G, Lallemant M, Nakalanzi S, Baptiste D, Walker AS, Gibb DM, Judd A. Antivir Ther. 2016 Apr 29. doi: 10.3851/IMP3054.

3. HPV Involvement in Head and Neck Cancers: Comprehensive Assessment of Biomarkers in 3680 Patients. Castellsagué X, Alemany L, Quer M, Halec G, Quirós B, Tous S, Clavero O, Alòs L, Biegner T, Szafarowski T, Alejo M, Holzinger D, Cadena E, Claros E, Hall G, Laco J, Poljak M, Benevolo M, Kasamatsu E, Mehanna H, Ndiaye C, Guimerà N, Lloveras B, León X, Ruiz-Cabezas

JC, Alvarado-Cabrero I, Kang CS, Oh JK, Garcia-Rojo M, Iljazovic E, Ajayi OF, Duarte F, Nessa A, Tinoco L, Duran-Padilla MA, Pirog EC, Viarheichyk H, Morales H, Costes V, Félix A, Germar MJ, Mena M, Ruacan A, Jain A, Mehrotra R, Goodman MT, Lombardi LE, Ferrera A, Malami S, Albanesi EI, Dabed P, Molina C, López-Revilla R, Mandys V, González ME, Velasco J, Bravo IG, Quint W, Pawlita M, Muñoz N, de Sanjosé S, Xavier Bosch F; ICO International HPV in Head and Neck Cancer Study Group. J Natl Cancer Inst. 2016 Jan 28;108(6):djv403. doi: 10.1093/jnci/djv403. Print 2016 Jun.

4. HIV Drug Resistance Among Children Initiating First-Line Antiretroviral Treatment in Uganda. Kityo C, Sigaloff KC, Sonia Boender T, Kaudha E, Kayiwa J, Musiime V, Mukuye A, Kiconco M, Nankya I, Nakatudde-Katumba L, Calis JC, Rinke de Wit TF, Mugyenyi PN. AIDS Res Hum Retroviruses. 2016 Jul;32(7):628-35. doi: 10.1089/AID.2015.0215. Epub 2016 Feb 11.

5. Neurocognitive Function at the First-Line Failure and on the Second-Line Antiretroviral Therapy in Africa: Analyses From the EARNEST Trial. Kambugu A, Thompson J, Hakim J, Tumukunde D, van Oosterhout JJ, Mwebaze R, Hoppe A, Abach J, Kwobah C, Arenas-Pinto A, Walker SA, Paton NI; EARNEST Trial Team. J Acquir Immune Defic Syndr. 2016 Apr 15;71(5):506-13. doi: 10.1097/QAI.0000000000000898.

6. Cardiac Dysfunction Among Ugandan HIV-infected Children on Antiretroviral Therapy. Namuyonga J, Lubega S, Musiime V, Lwabi P, Lubega I. Pediatr Infect Dis J. 2016 Mar;35(3):e85- 8. doi: 10.1097/INF.0000000000000997.

7. Peripheral neuropathy in HIV patients in sub-Saharan Africa failing first-line therapy and the response to second-line ART in the EARNEST trial. Arenas-Pinto A, Thompson J, Musoro G, Musana H, Lugemwa A, Kambugu A, Mweemba A, Atwongyeire D, Thomason MJ, Walker AS, Paton NI; EARNEST Trial Team. J Neurovirol. 2016 Feb;22(1):104-13. doi: 10.1007/s13365-015- 0374-7. Epub 2015 Aug 25.

8. Effect of diurnal variation, CYP2B6 genotype and age on the pharmacokinetics of nevirapine in African children. Bienczak A, Cook A, Wiesner L, Mulenga V, Kityo C, Kekitiinwa A, Walker AS, Owen A, Gibb DM, Burger D, McIlleron H, Denti P. J Antimicrob Chemother. 2016 Oct 5. pii: dkw388.

9. Second-line HIV Treatment in Ugandan Children: Favorable Outcomes and No Protease Inhibitor Resistance. Boerma RS, Kityo C, Boender TS, Kaudha E, Kayiwa J, Musiime V, Mukuye A, Kiconco M, Nankya I, Nakatudde L, Mugyenyi PN, Boele van Hensbroek M, Rinke de Wit TF, Sigaloff KC, Calis JC. J Trop Pediatr. 2016 Sep 15. pii: fmw062.

10. Integrase inhibitor versus protease inhibitor based regimen for HIV-1 infected women (WAVES): a randomised, controlled, double-blind, phase 3 study. Squires K, Kityo C, Hodder S, Johnson M, Voronin E, Hagins D, Avihingsanon A, Koenig E, Jiang S, White K, Cheng A, Szwarcberg J, Cao H. Lancet HIV. 2016 Sep;3(9):e410-20. doi: 10.1016/S2352-3018(16)30016-9. Epub 2016 May 27.

11. Protease Inhibitor Resistance in the First 3 Years of Second-Line Antiretroviral Therapy for HIV-1 in Sub-Saharan Africa. Boender TS, Hamers RL, Ondoa P, Wellington M, Chimbetete C, Siwale M, Labib Maksimos EE, Balinda SN, Kityo CM, Adeyemo TA, Akanmu AS, Mandaliya K, Botes ME, Stevens W, Rinke de Wit TF, Sigaloff KC. J Infect Dis. 2016 Sep 15;214(6):873-83. doi: 10.1093/infdis/jiw219. Epub 2016 Jul 11.

12. Accumulation of HIV-1 drug resistance after continued virological failure on first-line ART in adults and children in sub-Saharan Africa. Boender TS, Kityo CM, Boerma RS, Hamers RL, Ondoa P, Wellington M, Siwale M, Nankya I, Kaudha E, Akanmu AS, Botes ME, Steegen K, Calis JC, Rinke de Wit TF, Sigaloff KC. J Antimicrob Chemother. 2016 Oct;71(10):2918-27. doi: 10.1093/jac/dkw218. Epub 2016 Jun 23.

13. Correction: Evidence for Reduced Drug Susceptibility without Emergence of Major Protease Mutations following Protease Inhibitor Monotherapy Failure in the SARA Trial. Sutherland KA, Parry CM, McCormick A, Kapaata A, Lyagoba F, Kaleebu P, Gilks CF, Goodall R, Spyer M, Kityo C, Pillay D, Gupta RK; DART Virology Group. PLoS One. 2016 Jun 2;11(6):e0157094. doi: 10.1371/journal.pone.0157094. eCollection 2016.

14. Plasma Efavirenz Exposure, Sex, and Age Predict Virological Response in HIV-Infected African Children. Bienczak A, Denti P, Cook A, Wiesner L, Mulenga V, Kityo C, Kekitiinwa A, Gibb DM, Burger D, Walker AS, McIlleron H. J Acquir Immune Defic Syndr. 2016 Oct 1;73(2):161-8. doi: 10.1097/QAI.0000000000001032.

15. Identification of gaps for implementation science in the HIV prevention, care and treatment cascade; a qualitative study in 19 districts in Uganda. Bajunirwe F, Tumwebaze F, Abongomera G, Akakimpa D, Kityo C, Mugyenyi PN. BMC Res Notes. 2016 Apr 14;9:217. doi: 10.1186/s13104- 016-2024-4.

16. Low-Frequency Drug Resistance in HIV-Infected Ugandans on Antiretroviral Treatment Is Associated with Regimen Failure. Kyeyune F, Gibson RM, Nankya I, Venner C, Metha S, Akao J, Ndashimye E, Kityo CM, Salata RA, Mugyenyi P, Arts EJ, Quiñones-Mateu ME. Antimicrob Agents Chemother. 2016 May 23;60(6):3380-97. doi: 10.1128/AAC.00038-16. Print 2016 Jun.

17. The impact of genetic polymorphisms on the pharmacokinetics of efavirenz in African children. Bienczak A, Cook A, Wiesner L, Olagunju A, Mulenga V, Kityo C, Kekitiinwa A, Owen A, Walker AS, Gibb DM, McIlleron H, Burger D, Denti P. Br J Clin Pharmacol. 2016 Jul;82(1):185- 98. doi: 10.1111/bcp.12934. Epub 2016 Apr 25.

18. Clinical Evaluation of an Affordable Qualitative Viral Failure Assay for HIV Using Dried Blood Spots in Uganda. Balinda SN, Ondoa P, Obuku EA, Kliphuis A, Egau I, Bronze M, Kasambula L, Schuurman R, Spieker N, Rinke de Wit TF, Kityo C; ART–A consortium. PLoS One. 2016 Jan 29;11(1):e0145110. doi: 10.1371/journal.pone.0145110. eCollection 2016.

19. Abacavir, zidovudine, or stavudine as paediatric tablets for African HIV-infected children (CHAPAS-3): an open-label, parallel-group, randomised controlled trial. Mulenga V, Musiime V, Kekitiinwa A, Cook AD, Abongomera G, Kenny J, Chabala C, Mirembe G, Asiimwe A, Owen- Powell E, Burger D, McIlleron H, Klein N, Chintu C, Thomason MJ, Kityo C, Walker AS, Gibb DM; CHAPAS-3 trial team. Lancet Infect Dis. 2016 Feb;16(2):169-79. doi: 10.1016/S1473- 3099(15)00319-9. Epub 2015 Oct 5.

20. Brief Report: Prevalence of Latent Rheumatic Heart Disease Among HIV-Infected Children in Kampala, Uganda. Gleason B, Mirembe G, Namuyonga J, Okello E, Lwabi P, Lubega I, Lubega S, Musiime V, Kityo C, Salata RA, Longenecker CT. J Acquir Immune Defic Syndr. 2016 Feb 1;71(2):196-9. doi: 10.1097/QAI.0000000000000827.

21. Reduced bacterial skin infections in HIV-infected African children randomized to long-term cotrimoxazole prophylaxis. Prendergast AJ, Bwakura-Dangarembizi M, Mugyenyi P, Lutaakome J, Kekitiinwa A, Thomason MJ, Gibb DM, Walker AS; ARROW Trial Team. AIDS. 2016 Sep 20.

22. Immediate Antiretroviral Therapy Reduces Risk of Infection-Related Cancer During Early HIV Infection. Borges ÁH, Neuhaus J, Babiker AG, Henry K, Jain MK, Palfreeman A, Mugyenyi P, Domingo P, Hoffmann C, Read TR, Pujari S, Meulbroek M, Johnson M, Wilkin T, Mitsuyasu R; INSIGHT START Study Group. Clin Infect Dis. 2016 Sep 8. pii: ciw621.

23. Affordable HIV drug-resistance testing for monitoring of antiretroviral therapy in sub-Saharan Africa. Inzaule SC, Ondoa P, Peter T, Mugyenyi PN, Stevens WS, de Wit TF, Hamers RL. Lancet Infect Dis. 2016 Aug 25. pii: S1473-3099(16)30118-9. doi: 10.1016/S1473-3099(16)30118-9.

24. Baseline Inflammatory Biomarkers Identify Subgroups of HIV-Infected African Children With Differing Responses to Antiretroviral Therapy. Prendergast AJ, Szubert AJ, Berejena C, Pimundu G, Pala P, Shonhai A, Musiime V, Bwakura-Dangarembizi M, Poulsom H, Hunter P, Musoke P, Kihembo M, Munderi P, Gibb DM, Spyer M, Walker AS, Klein N; ARROW Trial Team. J Infect Dis. 2016 Jul 15;214(2):226-36. doi: 10.1093/infdis/jiw148. Epub 2016 May 18.

25. Empirical tuberculosis therapy versus isoniazid in adult outpatients with advanced HIV initiating antiretroviral therapy (REMEMBER): a multicountry open-label randomised controlled trial. Hosseinipour MC, Bisson GP, Miyahara S, Sun X, Moses A, Riviere C, Kirui FK, Badal-Faesen S, Lagat D, Nyirenda M, Naidoo K, Hakim J, Mugyenyi P, Henostroza G, Leger PD, Lama JR, Mohapi L, Alave J, Mave V, Veloso VG, Pillay S, Kumarasamy N, Bao J, Hogg E, Jones L, Zolopa A, Kumwenda J, Gupta A; Adult AIDS Clinical Trials Group A5274 (REMEMBER) Study Team. Lancet. 2016 Mar 19;387(10024):1198-209. doi: 10.1016/S0140-6736(16)00546-8.

26. Tuberculosis incidence is high in HIV-infected African children but is reduced by co-trimoxazole and time on antiretroviral therapy. Crook AM, Turkova A, Musiime V, Bwakura-Dangarembizi M, Bakeera-Kitaka S, Nahirya-Ntege P, Thomason M, Mugyenyi P, Musoke P, Kekitiinwa A, Munderi P, Nathoo K, Prendergast AJ, Walker AS, Gibb DM; ARROW Trial Team. BMC Med. 2016 Mar 23;14:50. doi: 10.1186/s12916-016-0593-7.

27. Second-line HIV Treatment in Ugandan Children: Favorable Outcomes and No Protease Inhibitor Resistance. Boerma RS, Kityo C, Boender TS, Kaudha E, Kayiwa J, Musiime V, Mukuye A, Kiconco M, Nankya I, Nakatudde L, Mugyenyi PN, Boele van Hensbroek M, Rinke de Wit TF, Sigaloff KC, Calis JC. J Trop Pediatr. 2016 Sep 15. pii: fmw062.

28. Examining the relationship between psychological distress and adherence to anti-retroviral therapy among Ugandan adolescents living with HIV. Mutumba M, Musiime V, Lepkwoski JM, Harper GW, Snow RC, Resnicow K, Bauermeister JA. AIDS Care. 2016 Jul;28(7):807-15. doi: 10.1080/09540121.2015.1131966. Epub 2016 Jan 10.

29. Once vs twice-daily abacavir and lamivudine in African children. Musiime V, Kasirye P, Naidoo- James B, Nahirya-Ntege P, Mhute T, Cook A, Mugarura L, Munjoma M, Thoofer NK, Ndashimye E, Nankya I, Spyer MJ, Thomason MJ, Snowden W, Gibb DM, Walker AS; ARROW Trial Team. AIDS. 2016 Jul 17;30(11):1761-70. doi: 10.1097/QAD.0000000000001116.

30. Can abacavir be used safely in children without HLA testing? Musiime V, Prendergast AJ. Lancet HIV. 2016 Feb;3(2):e58-9. doi: 10.1016/S2352-3018(15)00228-3. Epub 2015 Dec 7. No abstract available.

Other important highlights;

JCRC acquired a new Apheresis machine, through the ACTG studies consortium courtesy of the Case Western Reserve University. This is the only machine of its nature in Uganda and among the very few within the sub-Saharan region. The Machine has the capacity to carry out procedures like exchange blood transfusion for persons with sickle cell disease as well as platelet, plasma, and mononuclear cell harvesting among other therapeutic and diagnostic procedures. The machine shall be used both for research and specialized medical care / diagnostics at the JCRC.

The newly acquired Apheresis Machine

ACTG;

The Joint Clinical Research Centre is one of the three highly productive AIDS Clinical Trial Group (ACTG) Clinical Research Sites (CRS) attached to the Case Western Reserve University / University Hospitals Clinical Trials Unit (Case CTU). The centre has successfully conducted ACTG trials since 2005 with excellent accruals and outstanding performance evaluations.

Accruals at JCRC

Protocol Number Number enrolled JCRC Recruitment Status (Year opened) at JCRC Target A5264 (2012) 59 30 In follow-up A5288 (2013) 81 20 In follow-up A5274 (2013) 50 50 Closed A5225 (2015) 57 Open Closed A5297 (2015) 1 10 Closed Sub-Studies

A5243 (2012) 274 Open Enrolling A5278s (2012) 19 30 Closed

The CRS has had an excellent subject retention rate and the absolute lost to study rate for the period January – December 2016 was 0.9%.The site data scores have ranged between 89.7% and 95.6%falling in the very good to outstanding range. This site has performed well and has in several instances met or exceeded expectations in all aspects of clinical trial performance.

JCRC CAB: During 2016, the JCRC CAB continued with its mission of linking, advising and educating the Community on involvement in HIV/AIDS Research. The CAB continues to reach out to the local communities and has participated and contributed to regional and international conferences on HIV/AIDS research.

The JCRC CAB along with CABs from the 5 major leading biomedical research institutions organized and participated in the 11th Annual Cross-CAB Network Forum, 23rd - 25th November, 2016. The forum was held in Rakai, Masaka where more than 100 community members attended. The theme of the forum was “Community Involvement; Key in realizing the 90-90-90 Vision”.

Members of the JCRC CAB attending a Community Advisory Board (CAB) Network Forum meeting November 2016 in Masaka

CAB members also joined JCRC in celebrating 25 year anniversary by taking part in a one day VTC event organised by JCRC at the Uganda Railway Grounds on November 6, 2016. The CAB members sensitized the community about the benefits of early testing, prevention measures like condoms and abstinence, adherence to drugs, positive living, nutrition, importance of disclosure, TB assessment and infection control.

The CAB has continued to conduct outreach programs in the communities. During these sessions they provide updates on ongoing and recently concluded research protocols. They also educate the communities on HIV/AIDS, general health and nutrition.

3. ADMINISTRATION AND FINANCE

The Directorate of administration and Finance includes the departments of; Finance, Business Development, Human Resources, Procurement, Estates, ICT Stores, Transport and Security.

Selected achievements;

a. ICT;

The success and sustainability of an organization highly depends on robust Information Communication Technology (ICT) systems. JCRC embarked on an upgrade strategy that involved procurement of the Laboratory Information Management System (LIMS), Integrated Clinical Enterprise Application (ICEA) and upgrade of Financial Management System (MS Dynamics Nav 2013R2). These upgrades went hand in hand with the streamlining of the ICT processes.

ICT Governance:

i. The JCRC ICT policy and the 4 year ICT Strategic plan were approved and are operational; all ICT manuals were revised and new ones developed in line with the ICT policy manual and 2 ICT staff were trained in Information Technology Infrastructure Library (ITIL) ii. The internet capacity was upgraded from 1MB to 20MB with back up internet link of 1MB that supports the operation of ICT critical applications when the main link is off. iii. As a measure to cut the cost of printing and stationery, centralized printers were installed at every office block. This has reduced the cost of stationary and cartridges by over 50%. iv. Disaster recovery plans were implemented as a means to ensure business continuity of the ICT critical resources. v. Local area network (LAN) was successfully extended to the new Radiology building and this has enabled effective communication and timely capture of client’s data. Extension to the Canteen block was also completed by May, 2016. vi. Most computers with legacy hardware and software were upgraded or replaced with the latest technologies. This resulted into fewer ICT help desk calls and has contributed towards successful deployment of new ICT systems. vii. JCRC with support from USAID embarked on the implementation of the electronic records management system to proactively manage both business content and records throughout the content lifecycle, from the point of creation through to disposal. This will significantly improve business

efficiency and productivity, information security, and operational cost savings. This is expected to end on March 2017.

viii. Implementation of Information Management System; Significant progress was made towards the implementation and upgrade of Finance Information System (FIMS-Navision 2013), Laboratory Information System (LIMS) and ICEA.

a. Systems Nav.2013. All financial transactions are being processed through the system. Fixed assets, payroll and financial balances can all be accessed through the new system. Key financial reports such as Cash report, Trial balance, Balance sheet, Fund Accountability (FAS) report, Budget Vs Actual etc, are now generated through the system. Final system modifications to the system are expected to be completed early 2017

b. JCRC implemented ICEA software at the clinic which was acquired from Infectious Diseases Institute (IDI). All patients visiting the facility are now captured within the system, patient illnesses, lab request/results, prescriptions and other details are all being captured within the system. A reporting portal, running on a web client has been developed to facilitate the reporting needs of the clinic. This reporting portal is dynamic, new reporting needs can be added into the system as and when required. More work remains with the ward module so as to effectively manage the in-patient data at the ward.

c. The laboratory information management system (LIMS) was also installed and operationalised. Training was conducted for all Laboratory staff and users had hands on experience with system and are now able use the system effectively. Laboratory equipment have been interfaced with LIMS and there is smooth flow of information between the systems

d. Integration of ICEA/LIMS; The integration of NAV with ICEA was completed. Patient prescriptions are done through ICEA and the drug details transferred and accessed into NAV for invoice generation. Integration of NAV with LIMS is near completion with a few more configurations are being done. The three systems (NAV/ICEA/LIMS) are expected to communicate to each other so as to facilitate efficient transfer of information between these systems. To-date, ICEA and LIMS are able to communicate. Lab test requests are made in ICEA and sent to LIMS for processing which has significantly reduced the patient waiting time and the potential loss of the results. In most cases the printing of results may not be necessary and hence reduced cost of stationery. b. Finance;

i. Finance compliance checklists; the strict enforcement of compliance checklists (i.e. Form 5, LPO, Payments, contracts and services, payroll, petty cash, project close out, revenue generation, funds transfer checklists etc) led to a higher compliance rate with auditing and federal standards thus increasing the organization’s credibility with granting authorities. This improved accountability of funds advanced to JCRC as a whole. ii. Finance System functionality and reporting; the department registered success in the implementation of the new Nav. dynamics finance system currently used by all finance staff. This led to more dependable, effective and efficient financial reporting.

25 iii. All prices for services rendered at JCRC were reviewed and implemented by July 2016 in order to match with the national medical & economic standards. iv. Finance supported and monitored the operations of the private clinic leading the attainment of over 75% of the set target. v. Fixed assets and inventory management; A detailed and comprehensive verification exercise, update of the fixed assets register and inventory into the Navision system was accomplished.

c. Human Resources; 1. The department oversaw a successful performance management exercise where all appraisals for all staff were done and a report summarizing general performance was made. All JCRC staff have fully signed and filed job descriptions. 2. All JCRC staff have renewed contracts and a contract tracking system has been established in the HR department that allows reminders to be sent to respective staff two months before their contracts expire. 3. JCRC Staff received a motivational talk from Mr. Musolini Ethan a renown motivational talker on 8th/April/2016 at JCRC Lubowa.

Fig. JCRC staff attending a motivational talk by Mr. Musolini Ethan

4. One team building activity was organized for all staff and the department anticipates that another will be organized before June, 2017. 5. The department drew up an annual leave schedule for all staff at JCRC. 6. An electronic file for each staff at JCRC was created using the MFI document solution software. HR is in the process of uploading these files with staff members soft copy documents.

26 d. JCRC Stores; The JCRC store underwent significant upgraded with the support of THALAS.

The inside view of the (JCRC laboratory store section)

Some of the installations made include; metallic shelves, smoke detectors and automatic temperature monitoring system. Other developments included; the purchase of safety wear and other equipment for staff safety. e. Estates;

Outsourcing of cleaning services; A policy was introduced to outsource services of a cleaning firm in order to cut costs and achieve higher efficiency. JCRC hired the services of Pelican Cleaners International to manage all cleaning and compound maintenance at JCRC effective from November 2016.

THALAS project;

The Targeted HIV/AIDS and Laboratory Services (THALAS) Project is implemented through a cooperative agreement between USAID/Uganda and the Joint Clinical Research Centre (JCRC).FY6, THALAS focused on the consolidation of achievements of the previous years, with greatest emphasis on maintaining the quality and accessibility of HIV/AIDS and TB services at the JCRC Lubowa clinic.

Program achievements include; 1

1. Integrated TB/HIV/AIDS services at the Lubowa clinic; facility based HIV testing and counselling (HTC) services were provided benefiting 1,041 clients aged 2 years and above and 319 infants had DNA PCR tests done in collaboration with CPHL. Of the 1,041 patients who had rapid HIV tests 304 (29 %) were identified as HIV positive while 4 (1.2 %) infants identified through DNA PCR. All the identified HIV positive patients were linked into care at the Lubowa facility. The high positivity rate among clients having rapid HIV/tests is mainly due to the fact that patients who come to the JCRC facility are usually highly suspicious of having contracted HIV.

2. As part of the HIV care and treatment package, the Lubowa facility enrolled 616 new patients into HIV care (4 % children < 15 years), and 465 patients were newly initiated on ART. The clinic received 127 patients as transfer-in while on already ART. 15,643 patients received at least a clinical assessment (WHO staging) OR CD4 count OR viral load, with children below 15 years contributing 7%, a small increase from the previous year when the children accounted for 6.7%. By the end of the year, 15,402 patients were active on antiretroviral treatment, and 7.1% of these were children. The reduction in number of children newly enrolled in care is evidence to the successful implementation of Option B+ for elimination of mother to child transmission of HIV program at the clinic.

3. JCRC Lubowa clinic is a referral facility and therefore receives patients from a number of health care facilities around Wakiso and other districts in Uganda, especially patients that need advanced HIV care and management. With PEPFAR support, JCRC is a pioneer and one of the few facilities providing third-line HIV treatment in Uganda. SCMS and Medical Access Uganda LTD (MAUL) have continued to supply third line drugs to JCRC as the MOH works towards putting in place mechanisms to ensure regular supplies of these commodities.

4. A total of 248 new pregnancies were registered at the JCRC Lubowa clinic and all the mothers were linked to and provided eMTCT services including ART (Option B+) as recommended by MOH. For PY6, 195 deliveries were reported, and babies are being followed up; however 15 babies were reported to have died before their first birth day, registering a 53% reduction in mortality among the under one year old from the previous year (i.e. 32 babies died in Y5). Some of the strategies implemented include enhancing the education of the pregnant mothers, encouraging them to deliver in health facilities, and empowering them to disclose their status so that appropriate measures can be provided to ensure they deliver HIV free babies. JCRC strengthened reproductive health education and family planning services for patients and provision and use of Family Planning services increased during this reporting period. Family planning services provided included barrier methods (male and female

condoms), as well as hormonal contraceptives (depo-provera, implants) and IUDs. A total of 3,824 clients were provided with at least one FP service which included assessment, counselling, a product and/or referral.

5. The majority of clients who get services at the JCRC Lubowa clinic are served on out-patient basis. However, 250 patients had complicated conditions that needed advanced care which was provided through the in-patient facility, managed by experienced clinicians and a nursing team well equipped to provide the needed care - including intensive care.

6. TB/HIV collaborative interventions including screening of all patients visiting the HIV clinic for TB using the Intensified Case Finding tool, TB treatment and follow up and TB infection control werefully integrated in the clinic operations at Lubowa during the year. All the 15,643 clients (100 %) who visited the clinic were screened for TB at each visit to the facility, leading to identification of 370 presumed TB cases. Further investigations through TB microscopy, GeneXpert and/or X-ray were done, a total of 117 patients were confirmed to have TB. The TB clinic also benefitted from assistance of the DETECT Child TB Project which has trained staff and enabled engagement of 2 VHTs. These VHTs have been trained and routinely undertake contact tracing and patient follow-up. During the year, 250 TB patients have been followed up:- 38 completed treatment, 9 died while 2 transferred out to other facilities nearer to their homes.

7. The JCRC laboratories continued to play a significant role in HIV/AIDS diagnosis and treatment monitoring, by providing timely and accurate information for use in patient management and disease surveillance. For this reporting period, the output of the labs included6,670 CD4 tests; 1,163 HIV Rapid tests; 2,005 CBC; 1,315 Creatinine;1,033 AST and 354 TB tests. During this year the outputs were mainly from the Lubowa laboratory. During this reporting period THALAS provided TA and facilitation for the JCRC laboratory staff to undertake WHO/SLMTA or LQMS training program to enhance performance of laboratories.

8. THALAS supported MOH health systems strengthening by participating and providing expertise at national level committees whereby the JCRC/THALAS lab staff were co-opted as members of the MoH National Laboratory Technical and Advisory committee while the JCRC physicians are active members of the national ART committee. The lab staff participated in Quality Assurance and Laboratory Policy Sub-committee activities.

9. THALAS project team worked closely with other implementing partners including SCMS, JMS and NMS to ensure uninterrupted availability and supply of drugs and other medical supplies for patient in care. Collaboration with National Medical Stores (NMS) was strengthened, resulting in increased access to cotrimoxazole, fluconazole, and family planning supplies. Oral morphine for use in the palliative care program was sourced from JMS with the technical assistance of Hospice and the Palliative Care Association of Uganda (PCAU). Discussions are on-going with MOH, to ensure JCRC is included on MOH master list for essential medicines and medical supplies by NMS. With support from PEPFAR/USAID, JCRC has also been listed on the facilities that will benefit from the Opportunistic infection (OI) medicines procured through MAUL.

10. USAID support through Leadership, Management and Governance (LMG) project TA to JCRC was carried forward by the Change champions, including THALAS chief of Party, and Deputy Executive Director. The Chief of Party held quarterly review meetings to monitor progress made with LMG project TA. LMG support enabled JCRC to consolidate sustainability initiatives including updating of the ICT policy manual through virtual support from the LMG ICT consultant. The revised ICT policy manual was approved by JCRC board of trustees.

11. Information management systems at JCRC continued to be supported through upgrade and provision for technical support to ensure JCRC’s institutional sustainability beyond THALAS Project. JCRC Consolidated the update and upgrade of information management software across the clinical, laboratory and financial departments. These improvements integrated the systems, allowing JCRC’s staff to share information across the three. Currently when a clinician orders laboratory tests for their patients, the test order and lab results are availed in the consulting room, saving both time and money. The three upgraded systems include Laboratory Information Management (LIMS), Integrated Clinic Enterprise Application (ICEA), and Microsoft Dynamics Nav R13. Integration of LMIS with ICEA was completed.

12. Additional sustainability strategies included provision of private clinical and laboratory services for the private sector and research institutions. The private clinic cumulatively registered 1060 clients (536 males and 424 females). The private clients received HCT, basic and advanced laboratory tests, hospitalization, X-ray, ARVs and Cotrimoxazole prophylaxis as well as other specialized HIV care. More efforts will be put in during the subsequent periods to create demand for the private services and also ensure they meet the quality expected by the users.

13. JCRC hosted the 8th Annual HIV update meeting on 28th– 30thSeptember 2016, funded by Simply Speaking HIV, in collaboration with University of Wisconsin, University of Minnesota and US commissioner Bud Selig. The meeting highlighted HIV research findings conducted in Uganda and globally including presentations from International HIV/AIDS conferences (CROI and IAC). The meeting gave an opportunity to clinicians to learn and share experiences in HIV/AIDS practice. This meeting was very successful, and as in the previous year it included participants from Uganda, Rwanda, Tanzania and Kenya.

ESP Project

Successful antiretroviral therapy (ART) necessitates effective monitoring and adherence. Current HIV management guidelines recommend HIV viral load (VL) as the most reliable monitoring tool for persons on antiretroviral therapy (ART).

Sustainable VL test for all persons on ART remains a challenge because of the cost of the test and current highly sophisticated technology that relies on stable electricity, and high cost of reagents. Additionally, RNA (the analyte used to measure VL in blood) is unstable, prone to degradation, and must be pure for an accurate VL test to be conducted. This makes the test heavily reliant on cold chain storage at the facility and in transit.

Fig. The JCRC Scientist extracting RNA for VL using the ESP device.

The government of Uganda, through Uganda National Council of Science and Technology (UNCST) has facilitated JCRC to develop an innovative home-grown viral load test known as the Exclusion-based Sample Preparation and Generic Reagents to Reduce HIV Viral Load Assay Cost (ESP) VL. This locally generated innovation has proved that the VL test can be done on a simpler, cheaper and less sophisticated platform, reduce reliance on electricity, with less complex procedures and using cheaper generic reagents.

The ESP project is in the process of applying for WHO certification for this low cost VL testing platform. Approval by WHO demonstrates compliance with international standards paving the way for its wide spread use.

Objectives of the ESP project

1. Test and compare the VL measuring performance of an improved second generation HIV RNA extraction ESP device used with low-cost RT-PCR reagents against the existing “Gold Standard” VL assay. 2. Collect more comprehensive ESP technology performance data, to enable WHO assay certification. 3. Establish local capacity for manufacturing the ESP device and in vitro test kit. 4. Assess the needs for general implementation of the ESP VL technology and formulate a plan for appropriate dissemination of the ESP VL technology in Uganda

Institutional Collaboration for Technology Transfer

Achievements 1. Successfully compared and optimized the ESP platform to Abbott, the current gold standard for VL

2. Fully validated and quantified a set of generic “home brew” reagents that will be used to extract RNA from plasma on the ESP device 3. Conducted a Good Manufacturing Practice (GMP) training for selected JCRC laboratory personnel

JCRC Staff undergoing training in GMP

4. Developed SOPs and guidelines for the performance and interpretation of ESP VL tests 5. Conducted a business environment assessment among Private, Private Not-For-Profit, Public and Faith-based institutions

UNCST Monitors on a tour of the JCRC Laboratory at Lubowa

ESP next steps

In the next phase, we propose to demonstrate that this VL kit and platform can be locally produced, scaled up, fully supported, and integrated into the existing healthcare system. We will also evaluate various options for stabilizing RNA in order to address degradation over time, which ultimately affects the accuracy of VL tests. This will significantly improve the health outcomes for persons infected with HIV, through access to faster and affordable monitoring of treatment. As JCRC takes bold steps in production of medical diagnostics, there will also be direct economic benefit to Uganda through manufacturing of consumables by local industries.

Conclusion

This project’s novel low-cost method of measuring VL using exclusion-based extraction of RNA will potentially revolutionize access to appropriate monitoring for PLHIVs in Uganda. If the cost of a VL test can be made affordable, then more PLHIVs in Uganda will access this critical monitoring test. The more PLHIVs on ART receiving appropriate monitoring of treatment, the more they will achieve viral suppression. This initiative directly impacts on the National HIV/AIDS strategy and the UNAIDS 90-90-90 strategy, aimed at stopping the HIV epidemic.

JCRC Regional Centres of Excellence(RCES)

The 5 JCRC RCEs support the centres research network by acting as recruitment and monitoring sites. Selected achievements for the3se centres include;

The RCEs are equipped to offer a wide range of diagnostic and monitoring laboratory tests including CD4, DNA, HIV RNA, HIV Rapid testing, HIV drug resistance, Syphilis tests, TB screening, hematology, chemistry, among others.

a. Mbarara RCE;

i. The centre has maintained collaborative links with partners such as Infectious diseases research collaboration (IDRC) SEARCH and CBK Studies where the centre provides tests like Viral Loads, Chemistries, CBC, CD4 and plasma sample storages.

ii. Attracted a new partner; Harvard University through the Massachusetts General Hospital-Mbarara University of Science and Technology collaboration (MGH-MUST Collaboration)-The 5-year REVAMP study for Viral and Resistance tests. iii. Research activities at the centre; Successfully closed out the REALITY Clinical Trial, Continued to manage the Rheumatic Heart Disease study well, increased recruitments and follow up for 92 patients, ODDYSSEY Clinical Trial was flagged off with lower site activation ongoing, publications under REALITY made and currently working on the EARNEST Trial Genital Secretions Sub-study. iv. Successfully completed renovation of the RCE building.

Mbarara RCE fully renovated

b. Gulu RCE

1. Strengthened strategic partnerships in the area which has strongly supported the recruitment of study patients for the LIVING study. Other new partnerships have been built to include ASSIST and SDS. 2. Binding and archiving of all presentations and publications was successfully achieved. c. F/Portal RCE;

1. Recruitment for the Prospective study of Lopinavir based ART for HIV Infected childreN Globally (LIVING study) enrolled 39 participantshaving started in June 2016 performing beyond expectations. 2. Successfully closed the REALITY study in March, 2016 3. Private clinic slowly picking up currently with 68 patients enrolled. d. Mbale RCE; 1. The laboratory participated in external quality assurance for hematology and CD4/CD8 from UKNEQAS. 2. Research documentation and archiving was enhanced. 3. Strategic agreements were signed as well as maintaining the ongoing contractual obligations with Mbale Regional Referral Hospital for extended tenancy and IDRC for continued Lab services support.

SELECTED PICTIURES FOR THE JCRC JUBILEE (25 YEARS) CELEBRATIONS

The celebration cake in form of the JCRC administrative block (left) and Some of the invited guests read through the celebration materials as they await the arrival of the chief guest.

Dr. Diana Atwine look on as Hon. Dr. Ruth Jane Acheng addresses the gathering during the function

Prof. Mbonye (JCRC 1st Director) address the congregation during the celebrations

Prof. Manfred Dietrich address the gathering.

Prof. Manfred Dietrich (right) received a plaque from the guest of Honor Rt. Hon Dr. Ruhakana Rugunda

The chief guest of Honor Rt. Hon Dr. Ruhakana Rugunda hands over a plaque to the Minister of Health Hon. Dr. Jane Ruth Aceng (left) while hands over presents to Dr. Henry Boom (right)

The Permanent secretary Ministry of Health Dr. Diana Atine (second left) and the JCRC chairman Prof. J.Opio Epelu (extreme right) receive their plaques

The chief guest Honor Rt. Hon Dr. Ruhakana Rugunda thanks Ms. Margaret Sacnho (USAID) for supporting JCRC while (right), Margaret and Dr. Seyoum display the plaque they received on behalf of USAID.

JCRC long serving staff (25 years) receive their recognition plaques from the guest of honour. Top to bottom they include; Ms. , John Okiror, Alfred Tumwesigye, Paul Tuhaise, Rose Byaruhanga, Dinah Tumukunde and Disan Mulima

Buffet prepared for the celebrants and (right) some of the guests receive their share

Staff Accomplishments;

Joint Clinical Centre (JCRC) is known for providing quality medical research and training, providing equitable and sustainable HIV/AIDS care and other health care services in Uganda and other parts of Africa.

U.S Ambassador Deborah Malac (right) handing over the 2016 PEPFA HERO AWARD TO Florence Kintu (Centre) at the US Embassy in Kampala. JCRC was represented by the Chief Nursing Officer Deborah Masiira (lest)

The staffs at JCRC have dedicated their lives to serve patients by ensuring quality and timely service is given to all patients that visit the centre. The year 2016, one of JCRC staff Ms. Florence Kintu (Data clerk at JCRC outpatient clinic) was selected among the best 5 2016 PEPFA hero awardees for her outstanding role in the care and treatment of people living with HIV/AIDS.

Sr. Angella Rweyoora JCRC Nurse from F/Portal RCE received an award from the president of Uganda for Distinguished Citizen during the women’s day at Kololo independent grounds.

JCRC Head Quarters, Lubowa

+256 414 210 147, +256 414 20114 7/46, +256 417 723 028 Fax: +256 414 342 632

JCRCMBALE:

Mbale RRH Outpatient Section along Pallisa road, Mbale District TEL: +256 454 435 730

JCRCFORTPORTAL:

Buhinga hospital, Kabarole District TEL: +256 382 277 233

JCRC GULU:

Koro Sub-County, Gulu Municipality TEL: +256 471 432 407

JCRC MBARARA:

Mbarara Regional Referral Hospital, Mbarara Municipality Tel: +256 485 433 545

JCRC KAKIRA:

Kakira Sub county, Jinja District Tel: +256 434-122011

Web site:www.jcrc.org.ug/ Facebook: https://www.facebook.com/Joint-Clinical-Research-Centre-Uganda- 269426913248277/ Twitter: https://twitter.com/JCRC41592426 Instagram: https://www.instagram.com/jointclinicalresearchcentre

JCRC CELEBRATES 25 YEARS OF QUALITY HIV/AIDS RESEARCH, 11TH NOVEMBER, 2016