CROI 2017 Abstract e-Book

Abstract eBook

Oral Abstracts

Results: Plasma CAB concentrations throughout weeks 1-15 were above 4xPA-IC90 and remained detectable until week 26. CAB concentrations in rectal, but not vaginal fluids, were also above 4xPA-IC90 throughout weeks 1-15. Median plasma viremia at the time of the first CAB LA injection was 7.8 log10 RNA copies/ml, fluctuated between undetectable (<50 copies) and 4.2 log10 RNA copies/ml throughout week 1-16 of treatment, and gradually increased to a plateau of ~4.0 log10 by week 19. Analysis of integrase sequences in plasma showed emergence of mutations in 3/6 macaques: one animal had G118R/A122T at weeks 8-23, one had E92G at week 20, and one had G140R at week 12, E92Q at weeks 12-19, and Q124R at weeks 22-26. The G118R/A122T and E92Q mutations were also detected in viruses from vaginal and rectal fluids. Phenotypic testing is needed to assess the level of CAB resistance conferred by these mutations. Conclusion: CAB initiation during acute infection frequently selects for mutations that are known to be associated with resistance to other INI including G118R, E92Q, and E92G. Some of the mutations were detected as early as 8 weeks and persisted during the pharmacologic tail. The finding of G118R and E92Q in rectal and vaginal fluid highlights risks of secondary transmission of these viruses. Our results reiterate the importance of strategies to prevent CAB LA PrEP initiation during undiagnosed HIV infection. 85 DAILY ORAL PREP IS EFFECTIVE AMONG WOMEN WITH ABNORMAL VAGINAL MICROBIOTA Renee Heffron 1 , R. Scott McClelland 1 , Jennifer Balkus 2 , Connie L. Celum 1 , Craig Cohen 3 , Nelly Mugo 4 , Elizabeth A. Bukusi 4 , Deborah J. Donnell 2 , Jared Baeten 1 , for the Partners PrEP Study Team 1 Univ of Washington, Seattle, WA, USA, 2 Fred Hutchinson Cancer Rsr Cntr, Seattle, WA, USA, 3 Univ of California San Francisco, San Francisco, CA, USA, 4 Kenya Med Rsr Inst, Nairobi, Kenya Background: Daily oral tenofovir-based PrEP demonstrated high efficacy in clinical trials for HIV prevention among women with high adherence. Recent data suggest that vaginal tenofovir gel may not effectively prevent HIV among women with bacterial vaginosis or other indicators of vaginal dysbiosis (e.g., non-Lactobacillus or Gardnerella¬ predominance). Those data raised concern whether daily oral tenofovir could be less effective among women with abnormal vaginal microbiota. Methods: Using data fromwomen in the Partners PrEP Study, a phase III placebo-controlled trial of daily oral PrEP conducted in Kenya and Uganda that had high (~80%) PrEP adherence and overall efficacy >70% in women, we assessed PrEP efficacy among subgroups of women defined by bacterial vaginosis status, measured annually. Nugent score by microscopy was used to measure bacterial vaginosis, with 0-3 indicating normal, 4-6 intermediate, and 7-10 bacterial vaginosis. We also considered the separate components of the Nugent score: detection of Gardnerella/Bacteroides and non-detection of Lactobacillus as markers of abnormal vaginal microbiota. Results: Of 1470 women, the median age was 33 years (13%were aged <25 years), and 24% had bacterial vaginosis at enrollment. PrEP had comparable efficacy for HIV prevention among women with normal microbiota (efficacy=77%), intermediate microbiota (73%), and bacterial vaginosis (63%) (interaction p-value=0.9, Figure). Similarly, PrEP efficacy was not different among women with detected versus undetected Gardnerella/Bacteroides (69% efficacy versus 77%, interaction p=0.7) and Lactobacillus (74% versus 70%, interaction p=0.9). Conclusion: Among African women with a high prevalence of bacterial vaginosis and high PrEP adherence, the efficacy of daily oral PrEP was not different among women with abnormal versus normal vaginal microbiota. Bacterial vaginosis and other indicators of vaginal dysbiosis do not diminish the efficacy of oral PrEP for HIV prevention.

Oral Abstracts

86LB IMPACT OF VAGINAL MICROBIOTA ON GENITAL TISSUE AND PLASMA CONCENTRATIONS OF TENOFOVIR Sharon L. Hillier 1 , Leslie A. Meyn 1 , Katherine Bunge 2 , Michele Austin 3 , Bernard J. Moncla 1 , Charlene S. Dezzutti 1 , Jill Schwartz 4 , Mark A. Marzinke 5 , Craig Hendrix 5 , Lisa C. Rohan 1 1 Univ of Pittsburgh, Pittsburgh, PA, USA, 2 Magee-Womens Hospital of UPMC, Pittsburgh, PA, USA, 3 Magee-Womens Rsr Inst, Pittsburgh, PA, USA, 4 CONRAD, Arlington, VA, USA, 5 Johns Hopkins Univ, Baltimore, MD, USA Background: Secondary analyses of CAPRISA 004 showed that women with a Lactobacillus dominant vaginal microbiota had higher detection of tenofovir (TFV) in cervicovaginal lavage (CVL) fluid than women with non-Lactobacillus dominant microbiota. The objective of this secondary analysis was to evaluate the impact of vaginal microbiota on TFV concentrations in the genital tract and plasma, and tenofovir diphosphate (TFV-dp) in genital tissues following timed vaginal application. Methods: 41 healthy HIV negative women (mean age 28, 71%white) used either TFV 1% gel (40 mg) or films (40 and 10 mg) for 6 days. After 6 self-administered doses, cervicovaginal fluid (CVF) was collected on the 7th day prior to the final dose. Women inserted the final dose in the clinic with confirmation of correct product placement. Two hours later, cervical biopsies were obtained for tissue TFV-dp. Plasma and CVL were collected for TFV quantification. Vaginal swabs for diagnosis of bacterial vaginosis (Nugent score) and quantitative PCR detection of G vaginalis (GVAG) and Atopobium vaginae (AVAG) were collected prior to product use. The relationship between vaginal microbiota and TFV concentrations was assessed using linear and quadratic regression models.

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CROI 2017