CROI 2016 Abstract eBook

Abstract Listing

Poster Abstracts

986 Combination HIV Prevention and HIV Incidence in a Ugandan Hotspot Fishing Community

Joseph Kagaayi 1 ; Mary K. Grabowski 2 ; Gertrude Nakigozi 3 ; Godfrey Kigozi 1 ; Fred Nalugoda 1 ; Robert Sekubugu 1 ; Ronald H. Gray 4 ; David Serwadda 5 ; Maria J.Wawer 4 ; Larry W. Chang 6 1 Rakai Hlth Scis Prog, Entebbe, Uganda; 2 Johns Hopkins Univ, Baltimore, MD, USA; 3 Rakai Hlth Scis Prog, Baltimore, MD, USA; 4 Johns Hopkins Bloomberg Sch of PH, Baltimore, MD, USA; 5 Makerere Univ Schoool of PH, Kampala, Uganda; 6 Johns Hopkins Univ Sch of Med, Baltimore, MD, USA Background: Targeted combination HIV prevention interventions have been advocated to control the HIV epidemic in high HIV incidence and prevalence hotspots in sub-Saharan Africa. However, there is limited empirical evidence on the population-level effects of these interventions. We present data on the rapid scale-up of treatment as prevention (TasP) and medical male circumcision (MMC) and trends in HIV incidence in a fishing community with high HIV prevalence (41%) in Rakai District, Uganda. Methods: Between November 2011 and May 2015, four survey rounds of the Rakai Community Cohort Study (RCCS), a population-based longitudinal study of HIV incidence, risk behaviors and HIV service utilization among residents aged 15-49, were conducted in a large Lake Victoria fishing village. HIV incidence was estimated as the number of new infections per 100 person years (py) between visits. We used multivariable Poisson regression models with generalized estimating equations, to estimate adjusted incidence rate ratios (aIRR) and 95% confidence intervals (95%CI) of HIV incidence comparing the period before the start of TasP and rapid scale-up of MMC (2011-2012) to periods after 2012. Results: 4,071 persons participated in at least one RCCS survey round. Average ART coverage among HIV-positive persons increased from 18.6% in November 2011 to 67.3% by May 2015, while MMC coverage among non-Muslimmen increased from 24.3% to 49.2% over the same time period. HIV incidence was 4.0/100py (95%CI: 2.6-5.7) between November 2011 and October 2012, falling to 3.3/100 py (95%CI: 2.4-4.5) between October 2012 and October 2014, and to 2.9/100 py (95%CI: 2.2-3.8) between October 2014 and May 2015. The aIRR comparing the period 2011-2012 to 2014-2015 was 0.75 (95% CI=0.47-1.20); the aIRR for men was 0.75 (95% CI=0.39-1.43) and 0.77 for women (95% CI=0.38- 1.56). Conclusions: Rapid scale-up of combination HIV prevention in very high risk fishing communities on Lake Victoria is feasible, and there is preliminary empirical evidence of the effects of these interventions in decreasing HIV incidence. 987 Genital Inflammation and HIV Shedding Post-Male Circumcision in Rakai, Uganda Eshan U. Patel 1 ; Mary K. Grabowski 2 ; Godfrey Kigozi 3 ; Ronald H. Gray 4 ; Andrew D. Redd 5 ; Allison R. Kirkpatrick 5 ; David Serwadda 6 ; Maria J.Wawer 4 ;Thomas C. Quinn 7 ; Aaron A.Tobian 7 1 NIH, Bethesda, MD, USA; 2 Johns Hopkins Univ, Baltimore, MD, USA; 3 Rakai Hlth Scis Prog, Entebbe, Uganda; 4 Johns Hopkins Bloomberg Sch of PH, Baltimore, MD, USA; 5 NIAID, NIH, Bethesda, MD, USA; 6 Makerere Univ Schoool of PH, Kampala, Uganda; 7 Johns Hopkins Univ Sch of Med, Baltimore, MD, USA Background: Among HIV infected men undergoing medical male circumcision (MC), resumption of sexual intercourse prior to wound healing is associated with increased risk of HIV transmission to female partners. We previously reported that penile HIV shedding increases post-MC. In this study, we examined the association between pro-inflammatory cytokines and penile HIV shedding. Methods: A prospective cohort study of 223 HIV-infected men undergoing dorsal slit MC was conducted between June 2009 and April 2012 in Rakai, Uganda. Preoperative and weekly penile lavages from 1-4 weeks post-MC (n=1034 visits) were tested for pro-inflammatory cytokines (IFN-γ, IL-10, IL-12p70, IL-13, IL-1β, IL-2, IL-4, IL-6, IL-8, and TNF-α) by an electrochemiluminescence immunoassay (Meso Scale Discovery Inc.). Cytokines with <1% detection (IFN-γ, IL-12p70, & IL-4) were excluded from analyses. Modified Poisson regression with generalized estimating equations and robust variance estimators were used to estimate prevalence risk ratios (PRRs) for penile HIV shedding at weeks 1-4 post-MC. Models were run for each cytokine individually. Among detectable samples, log 10 cytokine levels were compared by penile HIV shedding status using the Wilcoxon rank-sum test and correlations with penile log 10 HIV RNA were determined by Spearman’s rank-order test corrected for multiple comparisons (Bonferroni method). Results: Penile HIV and HSV-2 shedding was detected among 13.7% (141/1026) and 10.8% (87/805) of sample visits, respectively. Relative to baseline, detection of each cytokine was higher during wound healing weeks 1-3 post-MC ( P <0.01), except for IL-2 ( P =0.072; n=1031). Detection of all cytokines was lower among healed wounds ( P <0.01; n=791). Baseline plasma HIV VL, CD4 count, genital ulcer disease, and antiretroviral therapy were not associated with cytokine detection. HIV shedding 1-4 weeks post-MC was associated with the detection of IL-1β, IL-2, IL-6, IL-8, IL-13, and TNF-α after adjusting for HSV-2 shedding and study visit ( P <0.05; n=630). Log 10 IL-1β and IL-8 levels were higher among visits with HIV shedding than non-shedding visits 1-4 weeks post-MC ( P <0.01). Log 10 IL-1β, IL-6, IL-8, IL-13, and TNF-α levels were positively correlated with penile log 10 HIV RNA levels ( P< 0.01). Conclusions: An increase in genital pro-inflammatory cytokines is associated with HIV shedding fromMC wounds. Strategies to reduce genital inflammation post-MC and HIV shedding during wound healing may help to prevent male to female transmission.

Poster Abstracts

420

CROI 2016

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