CROI 2017 Abstract e-Book

Abstract eBook

Poster and Themed Discussion Abstracts

1 Univ of Sao Paulo, Sao Paulo, Brazil, 2 Centro de Referência e Treinamento DST/AIDS–SP, Sao Paulo, Brazil, 3 Oswaldo Cruz Fndn–Fiocruz, Rio de Janeiro, Brazil Background: PrEP is effective in preventing HIV transmission, but concerns about a potential upsurge in rates of sexually transmitted infections (STI) are reported. The most prevalent STI are the Chlamydia trachomatis (CT) and Neisseria gonorrheae (NG), often seen in extra-genital sites and as asymptomatic infections in men who have sex with men (MSM). Recent data demonstrate that T cell activation and lower T regulatory cell frequency are associated with increased risk for sexually acquired HIV. In this study, we examined the association between asymptomatic anal CT/NG infection and immune activation among healthy MSM enrolled in a PrEP study. Methods: From the 546 complete sample of the open-label demonstration study PrEP Brasil, 34 asymptomatic participants with a positive anal swab for CT and/or NG while negative for other STIs were selected as cases; 35 controls were randomly selected based on sample availability among asymptomatic participants with negative anal swab. Groups were similar regarding demographic and clinical characteristics. Peripheral blood mononuclear cells samples were analyzed by flow cytometry Results: Compared to controls, individuals with asymptomatic CT and/or NG infection had a higher frequency of HLA-DR+CD38+ CD8+ T cells (1.5 vs. 0.9% p<0.005), trends toward higher proportions of activation markers in the memory phenotype (naïve/NA:0.2 vs. 0.1%, p=0.09; central memory/CM:2.9 vs. 1.9%, p=0.07; transitional memory/TM:2.4 vs. 1.2%, p=0.02; effector memory/EM:2.0 vs. 1.4%, p=0.06; and terminal effector/TE:1.9 vs. 1.9%, p=0.4). Exhaustion and senescence markers were also statistically higher. The percentage of activated CD8+ T cell expressing PD-1 (0.9 vs. 0.5%, p<0.01), CD95 (1.5 vs. 0.8%, p<0.01) and co-expressing both markers (0.9 vs. 0.5%, p<0.01) were significantly higher. Conclusion: Asymptomatic CT/NG anal infection are associated with systemic activation of the CD8+ T cells, potentially increasing the risk of sexually-acquired HIV. These findings were observed in CM, TM and EM subsets which reinforced the data by a shift toward non-naïve phenotype. Considering the effect of immune activation on HIV-transmission risk and the prevalence of asymptomatic STIs among MSM, either persistent diagnosis strategies or regular empiric treatment should be explored as additional HIV-preventive tool. Rather than merely increasing the risk of other STIs, PrEP provides an excellent opportunity to identify patients with asymptomatic STIs and offer counseling, screening and treatment. 949 MUCOSAL INFLAMMATION ABROGATES TENOFOVIR-GEL–MEDIATED PROTECTION FROM HIV INFECTION Lyle McKinnon 1 , Lenine Liebenberg 2 , Nonhlanhla Yende 2 , Lindi Masson 3 , Angela Kashuba 4 , Derseree Archary 2 , Quarraisha Abdool Karim 2 , Salim Abdool Karim 2 , Jo-Ann Passmore 2 , for the CAPRISA Mucosal Immunology Collaboration 1 Univ of Manitoba, Winnipeg, Manitoba, Canada, 2 CAPRISA, Durban, South Africa, 3 Univ of Cape Town, Cape Town, South Africa, 4 Univ of North Carolina at Chapel Hill, Chapel Hill, NC, USA Background: Partial efficacy in preventing HIV infection has been demonstrated by several trials of pre-exposure prophylaxis (PrEP). While adherence is a major predictor of PrEP efficacy, whether additional, biological factors related to HIV susceptibility predict how well PrEP prevents HIV in various sub-groups remains unclear. We addressed this in a prospective cohort analysis of mucosal inflammation in the context of the CAPRISA 004 trial of tenofovir (TFV) 1% gel. Methods: All available cervicovaginal lavage (CVL) specimens from HIV uninfected visits (n=2,144 visits in n=774 participants) were assayed for cytokine analysis using Biorad multiplex kits. Inflammation was defined by the number of elevated cytokines (upper quartile) as per our published analyses (Masson et al Clin Infect Dis 2015). Survival analyses using Cox regression were used to determine TFV efficacy in inflammation-defined strata. Adherence was defined by >50% of sex acts covered by gel as per Abdool Karim et al Science 2010. Multivariate analyses were used to control for potential confounders. Results: Using a cytokine score to define inflammation we confirmed that inflammation was associated with HIV outcome at the cohort level in a prospective survival analysis (n=774). HIV risk increased in a step-wise fashion in those with 3, 4, 5, 6, and 7 elevated cytokines (all p<0.05), providing strata for subsequent TFV efficacy sub-analyses. TFV efficacy was not observed in any of the groups where inflammation was present, with estimates ranging from 4 to -136% (all p>0.1). Conversely, those without inflammation were protected by TFV with efficacy ranging from 39 to 59% (p<0.05 for 4 of 5 comparisons). Efficacy was further enhanced in the group without inflammation and good adherence, with estimates of 76, 63, and 57% in those with fewer than 3, 4, and 5 or more elevated cytokines and who used the gel at >50% of sex acts (all p<0.05). In contrast, TFV efficacy estimates in high adherers with inflammation were -13, -9, and -19% for the same groups (all p>0.1). Conclusion: Individuals with mucosal inflammation were not protected by TFV gel, and adherence to gel, while protective overall, was of no benefit in the group where inflammation was present. Together, these data suggest mucosal inflammation, combined with adherence, is a major determinant of TFV gel efficacy. The mechanisms that underlie this observation, and validation of these findings in additional cohorts including those using other PrEP regimens, require further study. 950 IS SYNDROMIC DIAGNOSIS OF REPRODUCTIVE TRACT INFECTIONS ANTIQUATED IN THE HIV ERA? Harriet Nuwagaba-Biribonwoha 1 , Hannah Chung 1 , Asungushe Kayombo 2 , Deodatha Mugisha 1 , Kokuhumbya Kazaura 3 , Oscar Ernest 1 , Gissenge J. Lija 4 , Deborah Kajoka 4 , Jessica E. Justman 1 , Elaine J. Abrams 1 1 ICAP at Columbia Univ, New York, NY, USA, 2 Natl Inst of Med Rsr, Mwanza, Tanzania, 3 CDC Tanzania, Dar es Salaam, Tanzania, 4 Tanzania Ministry of Hlth, Community Development, Gender, Elderly and Children, Dar es Salaam, Tanzania Background: Syndromic diagnosis (SD) of reproductive tract infections (RTIs), based on patient signs and symptoms, is a widely implemented strategy in sub-Saharan Africa. We assessed sensitivity and specificity of SD against laboratory testing for RTIs among recently-diagnosed HIV-infected patients in Tanzania. Methods: A cross-sectional study was conducted among sexually-active HIV-positive adults ≥ 18 years (y) newly enrolling at the regional hospital HIV clinic in Bukoba Tanzania, 2012-14. Study procedures included an interview on current RTI symptoms (sores, discharge, dysuria), and a genital exam. A study nurse made the SD according to national RTI guidelines, verified by a medical doctor. Regardless of symptoms, laboratory testing of blood, urine samples and genital swabs for chlamydia trachomatis, neisseria gonorrhoea, herpes simplex virus 1/2, and treponema pallidumwas conducted. Among women, we also tested for trichomonas vaginalis, bacterial vaginosis and vaginal candidiasis. We analyzed the sensitivity and specificity of syndromic RTI diagnosis against a gold standard of laboratory testing, and determined the positive and negative predictive values (PPV, NPV). Results: We enrolled 615 participants: 301 men, median age 35.8y (IQR (30-41) and 314 women, median age, 33.2y (IQR 27-38). Half the men (56.2%) and 42.7% of women were married, median number of sexual partners in the previous 6 months was 1 for both. Median CD4 cell count was 249cells/µL (IQR 82-398) among men and 294cells/µL (IQR 132-486), among women. One third of men were circumcised (34.2%) at a median age of 10 years (IQR 3-19). Among 301 men, 58(19.3%) reported genital symptoms, 53(17.6%) had signs on examination; and 83(27.6%) had a syndromic RTI diagnosis. Among women 117(37.3%) reported symptoms, 67 (21.3%) had signs, and 184(58.6%) had a syndromic RTI diagnosis. On laboratory testing, 108 (35.9%) men and 247 (78.7%) women has RTIs. Among men, SD had a sensitivity of 37% (95% CI 28%-47%) and a specificity of 77% (95% CI 71%-83%), with a PPV of 1.66 (1.16-2.38) and NPV of 0.81 (0.69-0.95). Among women, SD had a sensitivity of 62% (95% CI 55-68%) and a specificity of 52% (95% CI 40%-65%), with a PPV of 1.29 (0.98-1.68) and a NPV of 0.74 (0.56-0.97). Conclusion: RTI prevalence was high. SD underestimated RTI prevalence in comparison to laboratory testing, particularly among men. Routine RTI screening through physical exam and laboratory testing should be implemented for all adults recently diagnosed with HIV. 951 DOES THE E138A MUTATION IN ASPIRE SEROCONVERTERS AFFECT SUSCEPTIBILITY TO DAPIVIRINE? Kerri Penrose 1 , Breanna J. Goetz 1 , Kelley C. Gordon 1 , Daniel W. Szydlo 2 , Marla J. Husnik 2 , Thesla Palanee-Phillips 3 , Jared Baeten 4 , John Mellors 1 , Urvi Parikh 1 , for the MTN020/ASPIRE StudyTeam

Poster and Themed Discussion Abstracts

CROI 2017 411