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Lack of Effectiveness of ART as an HIV Prevention Tool for Sero -discordant Couples in a Rural ART Program in Uganda. J Birungi , H Wang, M Ngolobe , K Muldoon, S Khanakwa , R King, P Kaleebu , K Shannon, L Lourenco, J Min, J Montaner , E Mills, Y Chen, DM Moore. Background. - PowerPoint PPT PresentationTRANSCRIPT
Lack of Effectiveness of ART as an HIV Prevention Tool for Sero-discordant Couples in a Rural ART Program in
Uganda
J Birungi, H Wang, M Ngolobe, K Muldoon, S Khanakwa, R King, P Kaleebu, K Shannon, L Lourenco, J Min, J Montaner, E
Mills, Y Chen, DM Moore
Background• ART coverage has expanded to > 8 million people worldwide.
• Expansion of ART has been associated with reductions in new HIV diagnoses in industrialized countries.
• HPTN 052 found 96% efficacy of early ART in preventing HIV transmission in sero-discordant couples.
HAARP study conducted at a rural TASO HIV clinic-HAARP study “The Highly Active Anti-retroviral therapy as Prevention” Study funded by CHIR and CANFAR
- TASO stands for The AIDS Support Organization
-TASO is an NGO with 11 HIV Clinic across Uganda
-0ver 80,000 HIV positive Registered clients with 50,000 receiving HAART funded by PEPFAR
HAARP study site
Study Objective
• To examine the effectiveness of ART as prevention among sero-discordant couples in a programmatic setting in rural Uganda, without routine access to VL testing.
• Compare couples where the HIV +ve partner was on HAART with those whose partner was not yet on HAART.
Primary end point:
• HIV incidence among co-habiting/married, stable, sexual partners of HIV-positive TASO clients.
Study Design
Methods• Enrolled two groups of HIV sero-discordant couples:
– ART group : HIV -positive partner was receiving ART (CD4≤250 or WHO stage IV illness)
– Non-ART group: HIV positive partner not yet eligible for ART
• Both groups received HIV risk-reduction counseling and condoms every 3 months.
• HIV negative partner tested for HIV every 3 months.
Methods (continued)• Plasma and serum collected every 6 months
– VL testing at the end of study or on last sample prior to sero-conversion.
– HSV-2 testing conducted on enrollment samples (and repeated on last sample for those tested negative).
– Genotypic sequencing for new infections where VL ≥ 1000 copies/ mL.
Analytic Methods • Compared ART and non-ART couples using Wilcoxon Rank
Sum and Chi-squared tests.
• Calculated incidence rate ratios- ART Group Requirement: Received ART for >3 months
• Cox proportional hazards modeling with ART as a time-dependent variable.
Results • Enrolled 586 couples.
• 348 (59%) of the positive participants received ART during the study– 249 on ART at enrollment– 99 began ART after enrollment
• Median ART-use at enrollment (for participants on ART) was 2.5 years.
Baseline characteristics
Not ever on ART (n = 238)
Began ART during the study(n =99 )
On ART at enrollment
(n = 249)
P- value
CD4 cell count at enrollmentMedian (IQR) 515 (389 - 684) 248 (156 - 366) 392 (240 - 539) <0.001
HIV positive participant is male (%) 121 (51%) 60 (61%) 150 (60%) 0.074
Age of male partner Median (IQR) 40 (34 - 47) 41 (36 - 50) 43 (37 - 50) 0.002Age of female partnerMedian (IQR) 33 (29 - 40) 36 (30 - 40) 36 (30 - 40) 0.002 Always use condoms (male response) 138 (58%) 61 (62%) 167 (67%) 0.003Duration (years) of relationship Median (IQR) 10 (5 - 18) 12 (6 - 22) 12 (6 - 21) 0.018
Circumcision Status of male partner 102 (43%) 44 (45%) 83 (34%) 0.053
HSV2 sero-positive (HIV negative participant) 183 (77%) 84 (87%) 203 (83%) 0.067
Results - Baseline Characteristics• ART couples were more likely to report
– Condom-use at last sex (67% vs. 58%; p = 0.003)– Longer relationships (12 vs. 10 years; p=0.018)
• ART couples were older– Median 43 vs. 40 years for men; – 36 vs. 33 years for women; p =0.002, for both
• ART couples had – Lower rates of circumcision (p= 0.053)
• No differences between the two groups in: – Polygamy; Pregnancy intentions; Injectable contraception-use
Results - HIV Incidence• Median follow-up was 1.3 years • 17 infections diagnosed in follow-up
– 9 (ART group)– 8 (non-ART group)
• Incidence– 2.09 per 100 pyrs for ART group– 2.30 per 100 pyrs for non-ART group– Incidence Rate Ratio of 0.91 among ART participants (p=0.84)
• Only 7% of all ART pts had VL >1000 copies/ mL• 3/7 (43%) of ART sero-converters • 7/7 (100%) of non-ART sero-converters
• Only 3 virus pairs currently sequenced of non-ART couples– 2 of 3 were linked transmissions
Determinants of Seroconversion Seroconverters
(n=17)No seroconversion
(n=527)P- value
ART use (at least 3 months) 9 (53%) 317 (60%) 0.550
HIV positive participant male (%) 13 (76%) 293 (56%) 0.088
>1 sexual partner reported by female 0 8 (2%) 0.999
Age of sexual debut (female) Median (IQR) 15 (14 -16) 16 (15 -18) 0.018
Male sexual decision making (male response)
10 (59%) 184 (35%) 0.044
Duration of relationship with primary partner (in years)
8 (5-12) 12 (6-20) 0.167
Polygamous partnership 8 (47%) 126 (24%) 0.042
Male partner circumcised 4 (24%) 210 (40%) 0.163
HSV2 positive (HIV negative partner) 13 (93%) 425 (81%) 0.592
VL >1000 copies/ mL 9 (64%) 168 (35%) 0.027
Cox PH Modelling• Univariate – All participants– ART-use HR = 1.07 (0.41-2.80)
• Stratified analyses HR for ART use:
• 1.01 (0.34-3.03) in couples with uncircumcised men• 1.02 (0.13-7.85) in couples with circumcised men• 1.05 (0.35-3.18)in HIV negative participants who were HSV2 + at
enrollment• 1.03 (0.34-3.12) in couples where the HIV negative participant was
female
• Insufficient power for adjusted model
Conclusions• ART-use was not associated with reduced risk of
HIV transmission in this study• Reasons are unclear:
– ART use was associated with reduction in viral load– High VL was associated with increased transmission
• Possible explanations:– Single VL measurement is not reflective of true viremia– Underreporting of outside sexual partners– Co-factors facilitating transmission at low level viremia– Confounding factors not accounted for in our stratified analyses
• It is difficult to extrapolate the results of RCTs in ideal situations to real life setting in low-income countries
So, What does this mean for treatment as prevention?
• It is important to collect data on the real-world effectiveness of ART in terms of preventing HIV transmission among representative populations especially in Africa
• Our results do not question that ART works as a
prevention tool, only that the effect can be undermined by other biological, social and cultural factors which also affect HIV transmission risk.
Acknowledgments• TASO Uganda Senior
Management– Robert Ochai E.D.
• TASO Jinja Staff• Medical Research Council• Study participants• Dr. Christine Nabiryo• Dr. Alex Coutinho• Dr. Heiner Grosskurth• Canadian Institutes for Health
Research• Canadian Foundation for AIDS
Research• PEPFAR & American people
HAARP study team• David Moore PI• Pontiano Kaleebu Co-PI• Julio Montaner Co-PI• Moses Ngolobe • Maureen Nyonyintono • Sarah Khanakwa• Rachel King• Katie Muldoon, Lillian Lourenco • Hong Wang, Wendy Zhang, Yalin
Chen , Jeong Min• Kate Shannon, Ed Mills• CAPT network
Thank You