CROI 2017 Abstract e-Book

Abstract eBook

Poster and Themed Discussion Abstracts

1 Univ of Pittsburgh, Pittsburgh, PA, USA, 2 Statistical Cntr for HIV/AIDS Rsr and Prevention (SCHARP), Seattle, WA, USA, 3 Wits Reproductive Hlth and HIV Inst, Johannesburg, South Africa, 4 Univ of Washington, Seattle, WA, USA Background: The reverse transcriptase (RT) polymorphism E138A occurs naturally in 5% of treatment-naïve HIV-1-subtype C-infected individuals, but is also selected by the diarylpyrimidine (DAPY) class of NNRTIs causing 3-fold resistance to etravirine and rilpivirine. E138A could reduce the protective efficacy of the vaginal ring candidate dapivirine (DPV) in preventing HIV-1 infection. DPV resistance was investigated among recombinant subtype C viruses with E138A derived from seroconverters in ASPIRE. Methods: ASPIRE was a safety and effectiveness study of a DPV vaginal ring for HIV-1 prevention conducted at 15 sites in South Africa, Zimbabwe, Malawi and Uganda. Population sequencing of protease and RT (amino acids 1-560) was performed on plasma samples from 164 seroconverters with HIV-1 RNA levels ≥200 copies/ml using an in-house assay. Drug resistance mutations (DRM) were identified using the Stanford HIVdb program v7.0. DPV susceptibility of plasma-derived recombinant HIV-1 containing bulk-cloned full- length RT sequences from ASPIRE seroconverters with E138A was determined in TZM-bl cells. Fold-change (FC) values were calculated using a mean IC 50 from a matched number of seroconverters without E138A from each arm. Statistical significance was calculated using Fisher›s Exact and Likelihood Ratio tests. Results: The frequency of E138A was not significantly different (p=1.0) between seroconverters in the DPV arm (3 of 68; 4.4%) vs. placebo arm (5 of 96; 5.2%) of ASPIRE. Of participants with E138A, 2 of 3 from the DPV arm (2.2-FC and 5.9-FC) and 2 of 5 from the placebo arm (3.4-FC and 4.1-FC) had significantly (p<0.05) higher IC 50 compared to participants with wild type virus (Table). Mean IC 50 values for E138A-containing HIV-1 from the DPV arm (2.1 nM) was not different from the placebo arm (2.7 nM; p=0.70). Conclusion: E138A is a naturally occurring polymorphism in HIV subtype C that is associated with modest reductions in DPV susceptibility in some RT backgrounds but not others. The frequency and extent of reduced susceptibility associated with E138A as the major variant was independent of the ASPIRE study arm. Although the low frequency of E138A limited the sample size, these phenotypic data provide reassurance that the E138A mutation was not selected by the DPV vaginal ring and is unlikely to reduce efficacy of the DPV vaginal ring for HIV-1 prevention.

Poster and Themed Discussion Abstracts

952 NNRTI-CONTAINING ART IS EFFECTIVE FOR DAPIVIRINE RING BREAKTHROUGH HIV-1 INFECTION Sharon Riddler 1 , Jennifer Balkus 2 , John Mellors 1 , Urvi Parikh 1 , Carolyne Akello 3 , Sufia Dadabhai 4 , Felix Mhlanga 5 , Colin O’Rourke 2 , Jared Baeten 6 , for the MTN-015 and MTN-020/ ASPIRE StudyTeams 1 Univ of Pittsburgh, Pittsburgh, PA, USA, 2 Fred Hutchinson Cancer Rsr Cntr, Seattle, WA, USA, 3 Makerere Univ-Johns Hopkins Univ Rsr Collab, Kampala, Uganda, 4 The Johns Hopkins Univ, Baltimore, MD, USA, 5 Univ of Zimbabwe, Harare, Zimbabwe, 6 Univ of Washington, Seattle, WA, USA Background: A vaginal ring containing dapivirine, a non-nucleoside reverse transcriptase inhibitor (NNRTI), was safe and effective in preventing HIV-1 infection in African women. Among women who acquired HIV-1 infection during the ASPIRE study conducted by the Microbicide Trials Network (MTN-020), NNRTI resistance associated mutations were detected in both dapivirine ring and placebo ring recipients with no significant difference between arms. NNRTI-based antiretroviral therapy (ART) remains the first-line standard of care in many regions of the world. The impact of dapivirine ring use at the time of HIV-1 acquisition on the subsequent response to NNRTI-containing ART is unknown. Methods: The virologic failure rate following initiation of ART was assessed among women who acquired HIV-1 infection during participation in MTN-020, a randomized, placebo- controlled trial of a monthly dapivirine vaginal ring. Virologic failure was defined as lack of suppression of plasma HIV-1 RNA to <200 copies/ml by 6 months after ART initiation or viral rebound to ≥200 copies/ml after initial suppression at any time. Results: Among 168 participants with incident HIV-1 infection during dapivirine or placebo ring use in MTN-020, 158 (94%; 65 dapivirine, 93 placebo) had at least 1 follow-up visit, of whom 78 (49%) initiated NNRTI-containing ART during follow-up (29 dapivirine, 49 placebo). The median time from estimated HIV-1 seroconversion to ART initiation was 10.3 months. The median time from ART initiation to HIV-1 RNA <200 copies/ml was approximately 90 days for both dapivirine and placebo ring recipients. The Cox proportional hazards model estimate for the likelihood of virologic suppression between the dapivirine ring and placebo ring arms was 1.0 (95% confidence interval 0.6-1.6). Among 57 women with at least 6 months of post-ART follow-up, 10 (17.5%) experienced virologic failure, 6/36 (16.7%) placebo ring recipients and 4/21 (19%) dapivirine ring recipients (P=0.82). Conclusion: Compared to placebo, we observed no difference in the time to virologic suppression or the risk of virologic failure for women who had received the dapivirine vaginal ring and then initiated NNRTI-containing ART. These results provide reassurance that standard WHO-recommended ART regimens are effective in the setting of breakthrough HIV-1 infection in women who had received the dapivirine vaginal ring, although continued monitoring of viorologic response is warranted. 953 ACUTE INFECTION WITH A WILD-TYPE HIV-1 VIRUS IN PREP USER WITH HIGH TDF LEVELS Elske Hoornenborg 1 , Godelieve J. de Bree 2 , for the Amsterdam PrEP Project in the HIVTransmission Elimination Amsterdam Consortium (H-Team)

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