CROI 2017 Abstract e-Book

Abstract eBook

Poster and Themed Discussion Abstracts

1 Pub Hlth Service Amsterdam, Amsterdam, Netherlands, 2 Academic Med Cntr, Amsterdam, Netherlands Background: Clinical trials show that pre-exposure prophylaxis (PrEP) with tenofovir/emtricitabine is highly effective against acquisition of HIV-infection. World-wide, only one case of PrEP failure was reported in an individual infected with a multi-class resistant virus under adequate tenofovir-diphosphate (TFV-DP) levels. We report a case with potentially very high HIV-1 exposure who was infected with wild-type HIV-1 while adhering well to a daily PrEP regimen. Methods: A 50-year-old men who has sex with men (MSM) started daily PrEP via the Amsterdam PrEP (AMPrEP) study. At enrollment, he tested HIV negative (4th generation HIV Ag/Ab test and HIV RNA test). Pill counts and daily diary information indicated adequate adherence of 7 pills per week. This was confirmed by a TDF-DP level in DBS of 2234 and 2258 fmol/punch at respectively 6 and 8 months after start of PrEP. HIV Ag/Ab tests during follow-up were repeatedly negative at 1, 3 and 6 months after starting PrEP. The number of episodes of condomless anal sex (CAS) was remarkably high (table 1). Results: Eight months after PrEP start, HIV seroconversion was observed with an indeterminate HIV Ag/Ab test (Ab positive, Ag negative). At the same day, the patient had a negative serum HIV RNA test (LOD 50 copies/mL) and western blot showed an atypical pattern characterized by a single p160 band. We were not able to detect HIV by nested pol PCR (DNA and RNA) on bulk peripheral blood mononuclear cells and sigmoid biopsies. Based on these findings and fear of inducing drug resistance, PrEP was stopped and the patient was monitored at weekly intervals. Three weeks after Ab seroconversion, HIV RNA was detected in his plasma (40,000 cop/ml) without detectable resistance mutations using routine clinical sequencing. Combination antiretroviral therapy was started resulting in an undetectable viral load after one month. Conclusion: Wild-type HIV-1 infection, despite confirmed adherence to PrEP, occurred in a MSM with potentially high HIV-1 exposure. It remains speculative why the patient seroconverted. The presence of an aberrant immune response under appropriate serum TDF levels raises the possibility that a very high HIV exposure, possibly in combination with inadequate TDF levels in gut mucosa may have led to infection. This case underscores the importance of counseling and monitoring PrEP users, including frequent HIV testing. Furthermore, we should be alert for atypical seroconversion resulting in indeterminate HIV Ag/Ab test in individuals on PrEP.

Poster and Themed Discussion Abstracts

954 HIV GENETIC DIVERSITY TO INFER PREP ADHERENCE AT THE ESTIMATED TIME OF INFECTION Olivia Council 1 , Susan Ruone 1 , Philip Mock 2 , George Khalil 1 , Marcel Curlin 3 , Walid Heneine 1 , Kachit Choopanya 4 , Michael Martin 2 , Gerardo Garcia-Lerma 1 1 CDC, Atlanta, GA, USA, 2 Thailand MOPH-US CDC Collab, Nonthaburi, Thailand, 3 Oregon Hlth and Scis Univ, Portland, OR, USA, 4 Bangkok Tenofovir Study Group, Bangkok, Thailand Background: Adherence in pre-exposure prophylaxis (PrEP) trials can be inferred by measuring drug concentrations at the time of HIV diagnosis. However, results do not necessarily reflect pill taking behavior around the time of HIV infection. The Bangkok Tenofovir Study (BTS) evaluated the efficacy of daily oral PrEP with tenofovir (TDF) among persons who inject drugs. We used molecular tools and adherence diaries from BTS participants to define pill taking behavior at the estimated time of infection Methods: HIV genetic diversity was studied in 11 participants who became infected with HIV during periods of daily directly observed therapy (DOT) with TDF and in 13 placebo recipients. HIV env (V1-V5) was amplified from plasma collected at the first nucleic acid test positive (NAT+) visit using single genome amplification. The diversity structure of the virus population seen in this sample was used to estimate time since infection (±95% confidence interval) using the Poisson-Fitter tool. The number of TDF doses taken within the confidence interval of infection were then computed from adherence diaries Results: The estimated time since infection in the TDF group ranged from 8 (95%CI=1-16) to 75 (49-100) days (median=41) and did not differ from that seen in the placebo group (median=15 days; p=0.433). Analysis of missed TDF doses within the estimated period when HIV infection occurred showed perfect adherence in 5/11 (45%) participants, nearly perfect adherence in two (67/69 and 95/100 possible doses taken), low adherence in one (52 out of 71 possible doses taken) and non-adherence (no TDF taken) in three. The 2-5 missed doses in the two participants with nearly perfect adherence were recorded immediately before (3-4 days) or after (1-2 days) the estimated day of infection. TDF exposure in adherent participants was associated with low plasma virus loads at the first NAT+ visit (13,465 RNA copies/ml vs. 294,000 in placebo infections; p=0.033) and infection with single variants (8/8 vs.8/13 in the placebo group; p=0.063) although the latter was not significant at the 0.05 level Conclusion: We used molecular tools to characterize adherence to PrEP at the estimated time of HIV infection, and demonstrated breakthrough infections under conditions of perfect or near perfect adherence to TDF. These results highlight the utility of molecular tools to improve computation of the biological efficacy of PrEP. Pre-diagnosis drug activity by PrEP reduces acute viremia and may favor the transmission of single variants 955 CHARACTERIZATION OF HIV SEROCONVERTERS IN A TDF/FTC PREP STUDY: HPTN 067 Mariya V. Sivay 1 , Yinfeng Zhang 1 , Sarah E. Hudelson 1 , Maoji Li 2 , Estelle Piwowar-Manning 1 , Mark A. Marzinke 1 , Kevin Bokoch 3 , Robert Grant 4 , Susan H. Eshleman 1 , for the HPTN 067 StudyTeam 1 The Johns Hopkins Univ, Baltimore, MD, USA, 2 Fred Hutchinson Cancer Rsr Cntr, Seattle, WA, USA, 3 FHI 360, Durham, NC, USA, 4 Univ of California San Francisco Gladstone Insts, San Francisco, CA, USA Background: HPTN 067/ADAPT evaluated tenofovir disoproxil fumarate/emtricitabine (TDF/FTC) regimens for pre-exposure prophylaxis (PrEP). HIV-uninfected women (South Africa) and men who have sex with men (Thailand, US) received 5 weekly observed doses of TDF/FTC (DOT), and were then randomized to a daily, time-driven (twice weekly + post-sex dose), or event-driven (before and after sex) TDF/FTC regimen. We analyzed data from subjects who seroconverted in the study.

CROI 2017 413