CROI 2015 Program and Abstracts

Abstract Listing

Oral Abstracts

Results: Men with DS had significantly thicker SC in their inner foreskin than uncircumcised men: 12.09um ± 2.92 versus 9.87um ± 2.54 respectively (n=16; p<0.001; 500 total measurements). In DS individuals, the inner and outer foreskin epithelium SA collectively showed significant difference (outer: 0.0457 ± 0.0108mm 2 ; inner:0.0285 ± 0.0078mm 2 ) (p<0.001; 160 total measurements)). This observation was shared with epithelium-dermis adhesion (outer: 2.4583 ± 0.7891;inner: 1.7878 ± 0.5510) (p<0.01). CD4 T cells were also observed in the inner and outer foreskin. Conclusions: The DS confers a degree of protection due to the inner foreskin SC thickening similar to the protective thick skin SC phenotype of outer foreskin. Beyond the protective primary barrier, the increased fragility of the inner foreskin in comparison to outer foreskin presents a new parameter that may account for the inner foreskin being a more vulnerable area. 1084 HSV-2 Shedding FromMale CircumcisionWounds Among HIV-Infected Men Mary K. Grabowski 1 ; Godfrey Kigozi 2 ; Ronald H. Gray 1 ; Jordyn L. Manucci 3 ; David Serwadda 4 ; Eshan U. Patel 3 ; Fred Nalugoda 2 ; Maria J.Wawer 1 ;Thomas C. Quinn 5 ; Aaron A.Tobian 3 1 Johns Hopkins Bloomberg School of Public Health, Baltimore, MD, US; 2 Rakai Health Sciences Program, Kalisizo, Uganda; 3 Johns Hopkins University School of Medicine, Baltimore, MD, US; 4 Makerere University College of Health Sciences, Kampala, Uganda; 5 National Institute of Allergy and Infectious Diseases (NIAID), Bethesda, MD, US Background: A randomized trial showed that although medical male circumcision (MMC) reduces herpes simplex virus type 2 (HSV-2) acquisition among men, MMC had no impact on HSV-2 transmission to female partners. We conducted a prospective observational study in Rakai, Uganda to assess HSV-2 shedding post-MMC. Methods: HSV-2 shedding was evaluated among 176 HIV and HSV-2 co-infected men (145 self-reported antiretroviral therapy (ART)-naïve, 9 self-reported ART use with detectable plasma viral load (VL), and 22 self-reported ART with undetectable plasma VL of <400 copies/mL). All men underwent dorsal slit MMC. HSV-2 serostatus was determined by an HSV-2 ELISA (Kalon Biological Ltd, Guilford, UK) with positive serology defined as an optical density index value ≥ 1.5. Preoperative and weekly penile lavages for 6 weeks were tested for HSV-2 shedding and viral load using a real-time quantitative PCR assay with primers to glycoprotein B. HSV-2 shedding was defined as >50 copies of HSV-2 DNA/mL on two separate runs. Prevalence risk ratios (PRRs) and 95%CI were estimated using Poisson regression with generalized estimating equations and robust variance. Results: HSV-2 shedding was detected in 9.7% (17/176) of men prior to MMC. There was a non-significant increase in the proportion of men with post-MMC HSV-2 shedding relative to baseline at weeks one (12.9%, 22/170, PRR=1.33, 95%CI=0.74-2.38, p=0.329) and two (14.8%, 23/155, PRR=1.50, 95%CI=0.86-2.38, p=0.153). HSV-2 shedding returned to baseline levels by week six after MMC (6.9%, 10/144, PRR=0.71, 95%CI=0.36-1.41, p=0.330). Post-operative HSV-2 shedding did not differ significantly between men who reported ART use compared to those who did not report ART use (PRR=0.67, 95%CI=0.24-1.80). HSV-2 shedding was lower among men with MMC wounds that were certified as healed (PRR=0.61, 95%CI=0.36-1.06, p=0.082). Among men with detectable HSV-2 shedding, the median HSV-2 log 10 VL/mL was elevated at week one (median=3.2, IQR=2.2- 4.8) compared to baseline (median=2.3, IQR=1.8-2.9), though this difference was not statistically significant (p=0.09.) Levels of HSV-2 among men with detectable shedding were similar to baseline at all other post-operative visits. Conclusions: Penile HSV-2 shedding was non-significantly increased during the first two weeks after MMC. Men undergoing MMC should be counseled on sexual abstinence until wound healing and consistent condom use thereafter. 1088 Self-Selection of Circumcision Acceptors, Risk Compensation and Effectiveness of Circumcision Among Service Recipients, Rakai, Uganda Joseph Kagaayi 1 ; Xiangrong Kong 2 ; Godfrey Kigozi 1 ; Fred Nalugoda 1 ; Steven J. Reynolds 3 ; David Serwadda 4 ; Nelson K. Sewankambo 5 ; Maria J.Wawer 2 ; Ronald H. Gray 2 1 Rakai Health Sciences Program, Entebbe, Uganda; 2 Johns Hopkins Bloomberg School of Public Health, Baltimore, MD, US; 3 Division of Intramural Research, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD, US; 4 Makerere University School of Public Health, Kampala, Uganda; 5 Makerere University College of Health Sciences, Kampala, Uganda Background: There are limited data on characteristics of acceptors of safe male circumcision (SMC), risk compensation and effectiveness of SMC service programs. We compared baseline characteristics of SMC acceptors and non-acceptors, determined the effectiveness of SMC and compared trends in sexual behaviors of the two groups using data on men aged 15-49 years enrolled in the Rakai community cohort study in Uganda. Methods: 1192 non-Muslim HIV-negative SMC acceptors were compared to a stratified random sample of 2384 uncircumcised men. Baseline behaviors and trends over time were compared using multivariable modified Poisson with generalized estimating equations. HIV incidence rates between the groups were compared using the incidence rate ratio (IRR) from a multivariable Poisson regression model. Results: Overall SMC acceptors were younger, less likely to be currently or previously married, and had higher education attainment. Among sexually active men, baseline sexual behaviors were comparable between the groups. However SMC acceptors had 26 percent higher prevalence of genital ulcers compared to non-acceptors (p=0.025). After circumcision, the rate of increase in prevalence of sexual activity was 2.6 percent higher among SMC acceptors (p<0.001) compared to non-acceptors. On stratification by age, the difference was 3.2 percent higher, p=0.08 among youths (15-24) but no difference was seen above 24 years. The prevalence of sexual activity with women in higher risk occupations (bar attendants, alcohol brewers, restaurant workers, itinerant traders, fisher folk, housemaids), increased by 10.2 percent per year among SMC acceptors (p=0.007) but no change occurred among uncircumcised men. Trends in other sexual behaviors were similar between the groups. HIV incidence among SMC acceptors was 0.61/100 person years and 1.11/ 100 person years among non-acceptors (adj. IRR=0.50, p=0.05, 95 percent CI=0.25-1.01). Conclusions: The higher prevalence of genital ulcers among sexually active SMC acceptors suggests that higher risk sexually active men self-selected to receive SMC. The suggestion of faster increase in sexual activity among circumcised youths and the increase in partnerships with higher risk women suggest possible behavioral disinhibition and need to be investigated in other settings. Though these behaviors, did not attenuate the effectiveness of SMC, there is need to add avoidance of high risk partners to the current SMC messaging. 4:00 pm– 6:00 pm NeuroAIDS Pathogenesis and Antiretroviral Therapy 56 Randomized Clinical Trial of Antiretroviral Therapy for Prevention of HAND Fujie Zhang 1 ; Robert Heaton 2 ; HaoWu 3 ; Hua Jin 2 ; Hongxin Zhao 4 ; XinYu 5 ; Donald Franklin 2 ;Weiwei Mu 1 ; FlorinVaida 2 ; Scott Letendre 2 1 Chinese Center for Disease Control and Prevention, Beijing, China; 2 University of California San Diego (UCSD), San Diego, CA, US; 3 Capital Medical University, Beijing You’an Hospital, Beijing, China; 4 Capital Medical University Beijing Ditan Hospital, Beijing, China; 5 Peking University, Beijing, China Background: Neurocognitive (NC) impairment (NCI) is common among treated HIV+ adults and can occur for several reasons, including production of viral proteins in the CNS, neuroinflammation, and antiretroviral therapy (ART) neurotoxicity. To date, clinical trials have focused on treatment of existing NCI and have been largely inconclusive. We conducted a clinical trial to determine whether one ART regimen would better prevent NCI than another. Session O-5 Oral Abstracts Room 613

Oral Abstracts

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CROI 2015