CROI 2017 Abstract e-Book

Abstract eBook

Oral Abstracts

Results: After 6 days of vaginal TFV use, trough TFV concentrations were lower in the CVF (P=0.032) and plasma (P=0.05) among women having higher levels of GVAG. Two hours after the final directly observed TFV product application, higher GVAG concentrations were significantly associated with decreased TFV-dp in cervical tissues (P=0.019) and lower TFV concentrations in plasma (P=.001, Figure 1A,B). There was also a linear association between increasing concentrations of AVAG and decreased TFV-dp in cervical tissue (P=0.006) and plasma concentrations of TFV (P=0.03). Women having Lactobacillus dominant microbiota (Nugent score 0-3) had significantly higher levels of TFV in the plasma (P=0.001) and TFV-dp in cervical tissues (P=0.045). CVL concentrations of TFV two hours after product application were not associated with vaginal microbiota (P>0.08). Conclusion: This study supports the CAPRISA findings and show that levels of TFV-dp in genital tissues and TFV in the plasma are correlated to markers of bacterial vaginosis (Nugent score, increased GVAG and AVAG). These data suggest that vaginal microbiota may impact the uptake of tenofovir when applied intravaginally. The mechanisms associated with reduced tenofovir uptake and its clinical implications require further study.

Oral Abstracts

87 ABUNDANCE OF PENILE ANAEROBES, IL-8, AND THE RISK OF HIV ACQUISITION, RAKAI, UGANDA Cindy M. Liu 1 , Jessica Prodger 2 , Aaron Tobian 2 , Rupert Kaul 3 , Alison Abraham 2 , Godfrey Kigozi 4 , Fred Nalugoda 4 , David Serwadda 5 , Lance Price 1 , Ronald H. Gray 2 1 George Washington Univ, Washington, DC, USA, 2 Johns Hopkins Univ, Baltimore, MD, USA, 3 Univ of Toronto, Toronto, Ontario, Canada, 4 Rakai Hlth Scis Prog, Kalisizo, Uganda, 5 Makerere Univ, Kampala, Uganda Background: The biological basis for the variability in HIV risk is not fully understood. The microbiome has been shown to affect the immune milieu of the genital mucosa, and we have shown that penile anaerobes were significantly decreased by medical male circumcision, which also reduced HIV acquisition. Thus, we hypothesize that genital microbiota may affect host susceptibility to HIV via immune activation. Methods: We conducted a case-control study using enrollment data from a male circumcision randomized trial in Rakai, Uganda. Cases (n=68) were men who acquired HIV during the 24-month follow-up and controls (n=199) were men who remained HIV-uninfected over the study period. Cases and controls were matched by randomization assignment. Real-time PCR and sequencing of the 16S rRNA V3V6 region of DNA extracted from eluent of sub-preputial swabs were used to estimate bacterial absolute abundance as the log 10 16S rRNA gene copies/swab. Logistic regression was used to assess the adjusted odds ratio (adjOR) of seroconversion associated with anaerobe abundance. Results: At enrollment, the cases had significantly higher abundance of penile anaerobes than controls, including Prevotella , Dialister , Finegoldia , and Peptostreptococcus . Higher abundance of penile anaerobes was associated with increased of HIV seroconversion (Table 1). The highest odds of HIV acquisition associated with each log 10 increase in abundance were for Prevotella (adjOR=1.54, 95% CI: 1.22-1.98), Finegoldia (adjOR=1.50, 95% CI: 1.12-2.07), Peptoniphilus (adjOR=1.48, 95% CI: 1.13-1.99), and Dialister (adjOR=1.47, 95% CI: 1.20-1.84). Cases were more likely than the controls to have detectable levels of IL-8, MCP-1, MIG, and MIP-3α (≥ 2 cytokines, p = 0.06). Additionally, sub-preputial IL-8 levels correlated significantly with anaerobe abundance. Conclusion: Penile anaerobes may play a role in HIV susceptibility in men comparable to bacterial vaginosis in women, suggesting the possibility that a sexually transmissible ecological imbalance increases HIV susceptibility in both sexes.

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CROI 2017