AIDSAIDS 20072007 WHAT IS NEW
ROBERTO CAUDA
Istituto di Clinica delle Malattie Infettive Università Cattolica Sacro Cuore Roma
THE HISTORY OF AIDS
• THE YEARS OF DESPERATION: 1984-1992
• THE HEROIC ERA: 1992-1996
• THE MIDDLE AGES: 1996-1999
• THE MODERN TIME: 1999-TODAY TherapyTherapy ofof PatientsPatients withwith HIVHIV InfectionInfection
Therapy of Opportunistic Infection
1° and 2° Prevention OIs
Antiretroviral Therapy
1980 1990 2000
Evolution of HIV infection: from lethality to long-term manageability
Rapidly Manageable Incremental therapeutic advances lethal long-term
HIV found Dual NRTI to be cause therapy of AIDS NNRTI-containing New HAART drug Antibody test classes? Entry RNA test Life inhibitors Life expectancy expectancy PI-containing <10 years Zidovudine HAART 20+ years QoL poor QoL good
1980 1985 1990 1995 2000 2005 2010 Novel Antiretrovirals in Development: Current Classes
Mature virus
Entry inhibitors TNX-355 CCR5 inhibitors CXCR4 inhibitors
MK-0518 GS-9137 Protease Integrase inhibitors inhibitors
Reverse transcriptase PA-457 inhibitors Timeline for New Antiretrovirals
PIs NNRTI CXCR4 Entry inhibitors inhibitors (eg, anti-gp120, CCR5) MK-0518 GS-9137 Maturation inhibitors CCR5 Integrase inhibitors inhibitors PA-457
2005 2006 2007 2008 2009
Darunavir TMC278
Etravirine Brecanavir
PROTEASE INHIBITOR OF SECOND GENERATION Tipranavir
§ Novel nonpeptidic protease inhibitor CH developed to provide a new treatment OH 3 option for PI-experienced patients Potent in vitro activity H C § 3 against WT HIV-1 and the majority of O O multiple PI-resistant HIV-1
NH § Requires co-administration with 200mg ritonavir SO2 § Available as a soft-gel capsule (250 N mg) F3C
11
POWER 1 and 2: VL < 50 copies/mL at Week 48 (ITT-TLOVR)
o Ongoing 96-week randomized 100 DRV/RTV 600/100 mg BID trial of 3-class experienced CPI/RTV pts (%) 80
1 primary PI mutation c/mL 45%* n ≥ 60 46%* n VL > 1000 copies/mL 40 o DRV/RTV 600/100 BID chosen as optimal dose 12% 20 10% at Week 24
Pts With VL < 50 0 o Superior efficacy at Week 48 over comparator 0 8 16 24 32 40 48 boosted PIs Weeks *P < .001 vs CPI/RTV. Not all patients reached Week 48 at the time of analysis; patients who had not reached Week 48 were censored
Lazzarin A, et al. IAC 2006. Abstract TUAB0104 at their last available visit.
MAIN OBSTACLES not enough potent ARTs Sanctuaries HIV-1 drug resistance Insufficient immune responses HIV-1 infected cells need to be recognized by the immune system INDUCING HIV’s “COMING OUT” INDUCE GENE EXPRESSION
-cytokines (IL-2, IL-6, IL-7) receptor
-anti-CD3 antibodies CD3
-prostratin, DPP, DAG lactones DAG
-valproic acid DNA histones acetate acetyl valproic acid histone deacetylases INDUCE GENE EXPRESSION
-cytokines (IL-2, IL-6, IL-7) receptor
-anti-CD3 antibodies CD3
-prostratin, DPP, DAG lactones DAG
-valproic acid DNA IMPROVED ART Integrase inhibitors:
a) O (18) coumarin-based 1995 OH OH inhibitor
O O O O H O OH b) H (10) equisetin 1995 N
O OH
OH (25) L-731,988 1999 c) N O O OH
F HN HN N d) N 1999 N (23) 5-CITEP O OH Cl
O S N O F N e) H 2002 N (31) L-870,810 N O OH
OH f) O N 2006 O Cl (34) JTK-303 / GS 9137 F O OH
Savarino A. Expert Opin. Investig. Drugs 2006 hydrophobic portion Chloroquine:
A)HIV-1 maturation inhibitor B)P-glycoprotein blocker Effects of chloroquine (CQ) on viral particle glycosylation Data #1 Data #1 [H3] glucosamine 200
150
cpm
cpm 100 cpm cpm cpm
50
0 0 0.0001 0.001 0.01 0.1 1 CQ conc. [mM]
[mM[mM CQ] CQ] [S35] cysteine / CQ conc.: 0mM 10-1mM 1 mM methionine 120 KDa
Savarino et al. JAIDS 2004 Figure: Can chloroquine interact with sugar-modifying enzymes? This computer-assisted simulation of ligand/protein docking by use of the program GOLD12 indicates that chloroquine (red) fits to the active site of UDP N-acetylglucosamine 2 epimerase (grey). This evidence suggests that chloroquine could inhibit the enzyme that catalyses the rate-determining step in the sialic acid biosynthetic pathway.
Savarino et al. Lancet Infect Dis 2006 Effects of quinoline X4 virus R5 virus antimalarials in combination with known antiretroviral AZT agents
Nevirapine
Lopinavir
Structure and mechanism of action of an ATP- binding cassette transporter
Reyes et al., Science 2005 Chloroquine acts as a chemosensitizer by increasing the intracellular concentrations of ABC substrates
Savarino et al. Lancet Oncol. 2006. Sanctuaries of HIV-1 Replication during Therapy •Brain •Lymphoid tissue •Testis
The P-glycoprotein is involved in drug efflux from these organs
Effects of mefloquine and chloroquine on the intracellular concentrations of LPV
Treatment quantity of LPV / 106 cells (ng)
uptake efflux
LPV 22.6 ± 4.2 2.6 ± 0.5
LPV + MQ 1mM 10.3 ± 6.1 3.2 ± 0.2
LPV + CQ 1mM 17.6 ± 3.2 12.3 ± 4.6
LPV + RTV 5mM n.d. 3.6 ± 0.6
Savarino A. et al. Drug Develop Res, 2007, in press. STEP-3: KILLING HIV-INFECTED CELLS Nature Medicine - 12, 1365 - 1371 (2006) NATURAL MECHANISMS OF HIV-1- INFECTED CELL KILLING
•Antibody-mediated killing •CD8 cell responses •Natural killer (NK) cells ANTIBODY-MEDIATED CELL CELL KILLING IMMUNOTOXINS IMMUNOTOXINS IN ANTI-HIV-1 STRATEGIES •Anti-gp120 antibodies conjugated with different toxins (e.g. Cholera toxin) •Effective and selective killing of HIV-1-infected cells. •Cell killing enhanced in the presence of chloroquine CD8-cell mediated cytotoxicity Comparsa di malattie opportunistiche in relazione al numero di linfociti T CD4 Up to what CD4 count is the risk of AIDS reduced if ART is started ?
100 CD4 count (95% CI) 0-49 50 50-199 200-349 350-499 note log scale 500+ – 10
5
1 Rate % of AIDS (per year)
0 .5 1 1.5 2 Years from start of ART ART-Cohort Collaboration 2004 Pre-therapy Median CD4 cell count in ART-naive patients initiating ART in Europe and North America
300
250
200
150
100
50
0 1995-6 1997 1998 1999 2000 2001 2002-3 Year of initiating ART # pts: 1232 4785 4583 3699 3203 2783 1932 ART Cohort Collaboration, Lancet, 2006 Impact of HAART on the Incidence of Opportunistic Infections
HAART
350 Any OI
300 yrs yrs - -
250
200
150 Incidence per 100 pt Incidence Incidence per 100 pt Incidence
1992 1993 1994 1995 1996 1997 Year Impact of HAART on the Incidence of Opportunistic Infections
HAART
140
120 yrs yrs - - PCP 100 MAC 80
60 CMV retinitis 40 Incidence per 100 pt Incidence Incidence per 100 pt Incidence Toxoplasmosis 20
1992 1993 1994 1995 1996 1997 1998 1999 Year IDSA 2001 Do Opportunistic Infections Occur in 2007? 8000 Opportunistic infections Therapy
4000 Pubblicazioni 0
1985/90 1991/96 1997/00 2001/06 Years Incidence of opportunistic infections for various CD4+ cell count strata:
Traditionally believed thresholds value indicated by the red line
CMV/MAC/TOXO PCP/OC PULMTB/EXPULMTB 100
10
1
0,1 Incidence per 1000 PYFU (95%CI)
0,01
<100 <100 <100 >=500 >=500 >=500 100-199200-299300-399400-499 100-199200-299300-399400-499 100-199200-299300-399400-499
Latest CD4 count (cells/ ml)
N OIs: 134 45 13 9 2 2 89 55 61 35 13 16 12 9 10 11 11 14
EuroSIDA: Podlekareva et al, JID 2006 Occurrence of OIs in ART-Naive Patients: The ALLRT Cohort
• ART-naive patients in ACTG trials included in A5001 (N = 2154) • Most common OIs: PCP, MAC, esophageal candidiasis • Most OIs occurred during first 2 months on HAART • No data reported on OI prophylaxis
*Multivariate model controlled for race.
Smurzynski M, et al. CROI 2006. Abstract 782. Incidence of AIDS-Defining Events After Initiation of HAART
Mycobacterium avium Disease Kaposi’s Sarcoma
25 25 20 20 15 15 10 10 Incidence Incidence 5 5 0 0 (per 1000 person years) (per
(per 1000 person years) (per 0-3 4-5 7-12 13-24 25-36 0-3 4-5 7-12 13-24 25-36 Period After Starting HAART (mo) Period After Starting HAART (mo)
Cytomegalovirus Disease Pneumocystis jiroveci Pneumonia
25 25 20 20 15 15 10 10 Incidence
5 Incidence 5
(per 1000 person years) (per 0 0
0-3 4-5 7-12 13-24 25-36 1000 person years) (per 0-3 4-5 7-12 13-24 25-36 Period After Starting HAART (mo) Period After Starting HAART (mo)
ART-CC: d’Arminio Monforte et al. Arch Intern Med. 2005 DEMOGRAPHIC CHARACTERISTICTS OF PATIENTS WITH THE FIRST AIDS RELATED EVENT UCSC (n=2.569)
1985/1994 1995/1996 1997/2000 2001/2006 (1294 pts) (476 pts) (407 pts) (392 pts) Age (years) (median, IQR) 33 (30-38) 35 (32-40) 38 (34-44) 42 (36-48)
Male sex (%) 80 74 74 74 Median CD4 (IQR) 17 (1-72) 20 (0-83) 40 (8-141) 68 (20-160)
Risk group (%) (sex/IDU) 43/46 38/51 62/26 64/23
Prior exposure to dual NRTI therapy (%) 5 13 10 12
Exposure to HAART (%) _ _ 14 24
Current HAART use (%) _ _ 12 24 Incidenza dei diversi tipi di primi eventi AIDS in relazione ad anno di calendario nella coorte UCSC
PCP 50 PML TBC 10 Toxoplasmosi Linfomi cerebrali 40 Candidosi CMV ADC SK 30 Micobatteriosi
5 Polmoniti batteriche 20 ricorrenti N° casi-anno casi-anno N° N° casi-anno casi-anno N°
10
0 0 1985/90 1991/96 1997/00 2001/06 1985/90 1991/96 1997/00 2001/06 PI INHIBIT PNEUMOCYSTIS CARINII
C. Atzori et al. JID, 2000 HIV unifected controls
No HAART HAART CD4>200 CD4>200
HAART No HAART CD4>250 CD4<200
Prevalence of main neurological disorders (%). (1154 patients notified between January 2000 and June 2004)
30 % 28.5 25
20
20.4 15
10 12.5 9.7 9.7 5 7.1
3.6 2.3 0 1.3 1.0 0.6 TE HIVE PML Crypto Other EUO PCNSL TB NHL CMV HSV
Dati del REGISTRO IRINA
PROGNOSTIC FACTORS OF AIDS- RELATED PML
372 PATIENTS
45 MILANO
20 ACTG 105 GESIDA 78 IRINA 48 UCSC
76 PARIS
De Luca et al. in progress Hazard ratios and relative 95% confidence intervals of PML-related death for cidofovir treatment versus no cidofovir treatment
10
1 Hazard Ratio for PML-related death
favors cART+CDV0,1 favors cART alone all Irina HSR Paris UCSC Gesida De Luca et al. in progress
OPPORTUNISTIC INFECTIONS IN THE PRE–HAART ERA
Tacconelli et al., Int J Tuberc Lung dis, 1997
Goletti et al., J Immunol, 1996
TB INCREASES HIV REPLICATION AND CAUSES A DECREASED SURVIVAL Impact of HAART on Incidence of TB in HIV-Infected Adults
• Adults TB Incidence During HAART • Initial reduction in TB 5.5 incidence 11% to 3% • Incidence remained low over 4.5 P trend = .02 5 years but still 1% per annum 3.5 on HAART 2.5 • Patients with TB responded to HAART but to lesser extent 1.5 than patients without TB 0.5
TB Incidence Rate (Cases/100 PYs) TB Incidence -0.5 1 2 3 4 5 Years of HAART
Lawn S, et al. CROI 2006. Abstract 68. Greatest Reduction in TB Incidence With Use of Both HAART and INH
• HIV dramatically increases TB incidence; HAART and isoniazid prophylaxis independently demonstrated to decrease TB incidence • Observational study in > 11,000 patients in Rio de Janeiro, Brazil: both interventions better than either alone
Golub JE, et al IAC 2006. Abstract MOPE0395. Prevalence of and Mortality From Extensively Drug–Resistant (XDR) TB
• Outbreak of highly drug–resistant TB reported at rural South African clinic, associated with high mortality
N = 1538 HIV+ pts n = 544 (33%) culture positive for TB
n = 221 (41%) resistant n = 53 (24% of MDR) resistant to isoniazid and rifampin to all TB drugs tested (XDR (MDR TB) TB)
52/53 died Median time to death: 16 days
Gandhi NR, et al. IAC 2006. Abstract THLB0210. Response to HAART Among Patients With Incident TB During ART
Median Viral Load Decreased Median CD4+ Cell Count Increased ³ 7 P < .001 600 6 P = .025 copies/mL
10 5 400
4 200 3
Median VL, log VL, Median 2 0
Baseline VL VL at TB cells/mm Count, CD4+ Median Baseline CD4+ Count CD4+ Count at TB
Lawn S, et al. CROI 2006. Abstract 68. Barillari G. et al Lancet Oncol., 2003 EFFECT OF HIV PROTEASE INHIBITORS ON CANDIDA
Sap inhibition by HIV-PI in vitro
Treatment Sap productiona (ng/ml) Effect of Protease Inhibitors None (control 1) 226.6 on Experimental Vaginal Candidiasis
+ DMSO 1% (control 2) 198.5 (12.4)b Saline Indinavir >100 + Pepstatin A, 100 mg/ml < 25 (>89) Ritonavir DMSO 80
+ Indinavir, 10 mM < 25 (>89) 3 “ 1 mM 53.3 (76.5) 60 “ 0.1 mM 207.2 (8.6) 40 ± SE x 10 CFU/ml x 10 ± SE + Ritonavir, 10 mM < 25 (>89) 20
55.8 (75.3) Mean < 10 194.5 (14.2) 0 2 6 10 15 a as detected by ELISA (see Ref. 16, 21) b % inhibition with respect to the DMSO (PI diluent) Days control 2.
A.Cassone,et al. JID, 1999 A. Cassone et al, JID, 2002 3D STRUCTURAL SUPERIMPOSITION BETWEEN C.ALBICANS SAP2 AND HIV-1 PROTEASE USING THE VAST ALGORITHM (ANDREA SAVARINO) A B
E. Tacconelli, et al. Curr. Med. Chem 2004
Sarcoma di Kaposi
P-gp and KS
bright dim 2% 91% SLKSLK - -uptakeuptake
dim bright 30% 66% SLKSLK - -effluxefflux
bright dim 86% SLK –efflux+ IDV 10% SLK –efflux+ IDV Lucia MB et al, JAIDS 2001 Lucia MB et al, JAIDS 2002
CAP in HIV-Infected and HIV-Uninfected IDUs
• ALIVE cohort, Time to First Bacterial Pneumonia by HIV Status and CD4+ Cell Count Baltimore, HIV negative HIV+/CD4+ ≥ 500 N = 3889 HIV+/CD4+ 200-499 HIV+/CD4+ 100-199 – Male: 75% HIV+/CD4+ < 100 1.00 – HIV positive: 24% 0.75 – Cigarette smokers: 85% 0.50 Free Probability • ↑ risk at lower CD4+ cell - counts 0.25 – 3-fold in HIV+ IDUs with 0.00 ↑ 0 5 10 15 20 CD4+ > 500 vs HIV-negative Pneumonia Years of Follow-up Stein K, et al. IACIDUs 2006. Abstract MOAB0303. – 20-fold ↑ at CD4+ < 200 vs Trends in CAP in HIV-Infected and HIV- Uninfected IDUs
HAART associated with 0.50 RH (95% CI: 0.26-0.94) for CAP HIV negative 14 HIV positive 45 % of Study Visits on HAART 12 HAART 40 PYs 35 10 30 8 25 6 20 15 4 10 2 5
Pneumonia Cases/100 Pneumonia 0 0 1989 1991 1993 1995 1997 1999 2001 2003 Calendar Year
Stein K, et al. IAC 2006. Abstract MOAB0303. Community-Acquired MRSA in HIV-Infected Patients in San Diego
• 40.4 cases/1000 PY in HIV-positive • Predictors of MRSA patients in 2005 – Recent receipt of β-lactam – 18-fold higher rate than HIV antibiotics negative •OR: 2.46; P = .001 18 16 MRSA Prevalence 1993-2005 – History of syphilis 14 •OR: 4.40; P = .01 12 10 – Current CD4+ cell count 8 •OR per 100 CD4+ cells: 6 0.84; P = .03 4 Number of Cases – Maximum log HIV viral load 2 10 0 •OR: 4.52; P < .001
1994 1995 1996 1997 1998 1999 2000 2001 2002 2003 2004 2005 Year Crum-Cianflone N, et al. IAC 2006. Abstract MOAB0304. Community-Acquired MRSA in HIV-Infected Patients in San Diego
•Update: 2006 •All initial isolates •435 HIV-infected patients sensitive to vancomycin with 12,118 person-years and minocycline of follow-up – One isolate developed minocycline resistance after initial treatment with – 29 (6.7%) of patients developed this antibiotic community-acquired MRSA infection •28/29 (97%) was •Abscess of the scrotum or sensitive to TMP-SMX buttocks was the most •4/29 (14%) sensitive to common presentation erythromycin Crum-Cianflone N, et al. IAC 2006. Abstract MOAB0304. Kaplan-Meier survival estimates for patients experiencing their first AIDS-defining episode in the UCSC cohort, stratified by calendar years
1,0 1,0
,9 ,9
,8 Pre-HAART era:1985/94 ,8 Dual NRTI era: 1995/96 ,7 ,7
,6 ,6
,5 ,5
,4 ,4 Cumulative Survival Cumulative survival
,3 ,3
,2 ,2 ,1 ,1 0 20 40 60 80 100 120 140 160 180 200 220 240 260 280 300 0 20 40 60 80 100 120 140 160 180 200 220 240 260 280 300
Time from first defining-AIDS episode(months (months)) Time from first defining-AIDS episode (months)
1,0 1,0
,9 ,9
,8 ,8
,7 ,7
,6 ,6
,5 Early HAART era: 1997/00 ,5 Late HAART era:2001/07 ,4 ,4 Cumulative survival C u m u l a t i v e s u r v i v a l
,3 ,3
,2 ,2
,1 ,1 0 20 40 60 80 100 120 140 160 180 200 220 240 260 280 300 0 20 40 60 80 100 120 140 160 180 200 220 240 260 280 300
Time from firts defing-AIDS episode (months) Time from first defing-AIDS episode (months) Predictors of time-to-death after the first AIDS-defining episode (multivariate Cox’s proportional hazards model)
HR for 95% CI P death
Age (per 10 years more) 1.17 1.06-1.24 <0.001
CD4 (per 100 cell/mm3 higher) 0.93 0.90-0.97 <0.001 Use of HAART before the 0.65 0.44-0.97 0.035 episode Use of mono-dual NRTI 0.80 0.63-1.02 0.075 before the episode
Calendar year (per year later) 0.86 0.85-0.87 <0.001 HIV VIREMIA AND T CD4+ POST HAART IN HIV+ OLDER PERSONS
M. Tumbarello et al. BMC Infect. Dis. 2004 M. Tumbarello et al. AIDS 2003 Mortality trends in HIV: HIV Outpatient Study (HOPS)
Proportion (%) of Deaths Due to Nonopportunistic Illnesses Contributing to Nonopportunistic Causes Death as a Percentage (%) of All Deaths Between 2000 and 2002 40 35.6 80 71.7 35 70 30 60 25 22.7 50 45.7 20 17.2 40 15 30 9.8 10 20 5 10 0 0 1996 2002 Renal Hepatic Pulmonary P<.0001 for trend Cardiovascular
Palella FJ et al. Presented at: 11th Conference on Retroviruses and Opportunistic Infections, 2004; Abstract 872. Incidenza di neoplasie AIDS-definienti e non in pazienti in HAART
DAD: D’arminio Monforte et al. CROI 2007 Predictors of Anal Dysplasia in HIV-Positive and HIV-Negative MSM
• UCSD anal dysplasia screening clinic[1]
– Pap screening not associated with decreased prevalence of invasive anal cancer, although earlier stage at detection suggested – Pap correlated with biopsy (increasingly so with increased operator experience) • Anal dysplasia referral population study[2]
– 36% of HIV-positive men and 30% of HIV-negative men had high-grade anal dysplasia – Pap results did not correlate with biopsy – ARV use and duration not predictive of high-grade anal dysplasia
1. Press N, et al. CROI 2006. Abstract 808. 2. Montaner J, et al. CROI 2006. Abstract 807. Substantial Increase in Incidence of Anal Cancer in France
• French National Hospital Database • 81,752 HIV-infected patients; 97 incident cases of anal cancer
120 Overall Non MSM MSM Women 66.4 100
80 29.9 36.6 60 24.9 16.0 40 13.7 9.7 10.3 12.7 3.6 20 2.7 0 Incidence/100,000 PY Incidence/100,000 0 < April 1996 April 1996 - Dec 1998 > Dec 1998
Picketty C, et al IAC 2006. Abstract TUAB0305. Deaths in D:A:D Multivariable relationships with death rate latest CD4 count Latest CD4 count <50 50-99 100-199 All-cause mortality 200-349 350-499 >500
<50 50-99 100-199 200-349 350-499 >500 Liver-related mortality 1 10 100 Relative rate (95% CI)
D:A:D study: Weber et al, Arch Intern Med 2006 Italian Cohort HIV / HCV CO-INFECTION I C O N A Naive Antiretroviral
0.15
progression 0.10 HBV-/HCV+-
clinical
with HBV-/HCV- 0.05
proportion
Cumulative Cumulative 0.00 0 500 1000 1500 Days from antiretroviral treatment start
A. De Luca et al. Arch. Intern. Med , 2002 AIDS 2003; 17(12):1803-1809 Mortality due to hepatitis C-related liver disease in HIV-infected patients in France (Mortavic 2001 study) Eric Rosenthal; Marilyne Poirée; Christian Pradier; Christian Perronne; Dominique Salmon-Ceron; Loic Geffray; Robert P. Myers; Philippe Morlat; Gilles Pialoux; Stanislas Pol; Patrice Cacoub; for the GERMIVIC Joint Study Group Lancet 2004
HAARTà death for liver failure An increasing proportion of US adults with AIDS are women
AIDS cases among women as % of all adult/adolescent cases in USA 1996–2001 28 26.2% 26.2%
24 23.1% 24.0% 24.4% 21.7% women as % as of all women AIDS cases among among cases AIDS adult/adolescent cases adult/adolescent 20 1996 1997 1998 1999 2000 2001 Year
CDC HIV/AIDS surveillance report: www.cdc.gov In Western Europe, women account for up to 32% of people with HIV/AIDS
Women aged 15–49 years with HIV/AIDS in Western Europe (end 1999)
32% 27% 20% 19% 21% 22%
UNAIDS, 2000; www.unaids.org Trends in Mother-to-Infant Transmission Rate and Maternal Antiretroviral Therapy, WITS, 1990-1999 60 100
90 50 HAART 80 None ZDV 70 40 Monotherapy 60 (prophylactic) 30 24.5 50 Multi-ART 40 20 22.7 Inflection Point 1 21.4 19.8 30 %Receiving Therapy ZDV 20 10 10.7 Inflection Point 2 Monotherapy 9.1 3.4 3.6 3.1 10 Transmission Rate per100 (maternal indications) 3.3 0 0 1990 1991 1992 1993 1994 1995 1996 1997 1998 1999 Year of Enrollment HAART reduces transmission of HIV from mother to child vs no treatment or zidovudine monotherapy
25 January 1990 to June 2000 20% 20 •2,549 HIV-infected pregnant women 15 •1,542 infants born 10.4% 10
5
(% of total births) (% of total 3.8% (% of total births) (% of total Transmission rate rate Transmission Transmission rate rate Transmission 1.2% 0 No ZDV multi-ART* HAART treatment monotherapy
* Multi-ART: dual antiretroviral therapy with no or one highly active drug
Cooper et al. JAIDS 2002; 29:484–494 Incidence of birth defects associated with first-trimester exposure to individual agents
No. of birth defects per 100 live births 6
4
3.4 3.2 3.0 3.1 2 2.5 1.9
0 Any PI Nelfinavir Any NNRTI NVP EFV CDC n = 537 n = 301 n = 279 n = 216 n = 88 Background
Antiretroviral Pregnancy Registry Steering Committee. Interim report for 1/1/89–31/7/02. Registry Project Office, 2002 Nov Increased soluble markers of endothelial dysfunction in HIV-positive patients under highly active antiretroviral therapy [RESEARCH LETTERS] de Gaetano Donati, Katleena; Rabagliati, Ricardoa,b; Tumbarello, Marioa; Tacconelli, Evelinaa; Amore, Concettac; Cauda, Robertoa; Lacoviello, Liciac