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Herpes simplex type 2 (HSV-2) is associated with HIV acquisition among both placebo and vaccine recipients in the STEP trial of the Merck Adenovirus 5 (MRKAd5) HIV-1 vaccine
Presented by Ruanne Barnabas (United States).
R. Barnabas1, Y. Huang2, H. Janes2, R. Morrow3, J. Fuchs4, K. Mark5, M. Casapia6, D. Mehrotra7, S. Buchbinder4, L. Corey1,3, J. Wasserheit1,8, NIAID HIV Vaccine Trials Network
1Fred Hutchinson Cancer Research Center, Vaccine and Infectious Diseases Institute, Seattle, United States, 2Fred Hutchinson Cancer Research Center, Statistical Center for HIV/AIDS Research and Prevention, Seattle, United States, 3University of Washington, Laboratory Medicine, Seattle, United States, 4San Francisco Department of Public Health, San Francisco, United States, 5University of Washington, Division of Infectious Diseases, Seattle, United States, 6Asociación Civil Selva Amazónica, Iquitos, Peru, 7Merck Research Laboratories, North Wales, United States, 8University of Washington, Department of Global Health, Seattle, United States
Background: The randomized clinical trial of the MRKAd5 HIV-1 vaccine (Step study) demonstrated that the vaccine did not prevent HIV infection or reduce early viral load (VL). Moreover, in some subgroups, HIV incidence was higher in vaccinees than in placebo recipients. HSV-2 infection is associated with increased risk of HIV acquisition and elevated HIV VL. We examined whether trial volunteers with HSV-2 antibodies at baseline had (1) increased HIV acquisition, (2) elevated VL and/or (3) faster time to ART initiation.
Methods: HSV-2 associations were explored using the primary analysis data-set of 1836 men from North and South America, the Caribbean and Australia, including 88 men infected with HIV prior to unblinding. HSV-2 serostatus was determined by Western blot (WB) and HIV was diagnosed by immunoassay with WB confirmation. Cox proportional hazards regression models were used to estimate the association between HSV-2 seropositivity and HIV acquisition and time to ART initiation among HIV seropositives. The association between HSV-2 seropositivity and early pre-ART VL was assessed using linear regression.
Results: Baseline HSV-2 seroprevalence was 30% (n=550). HSV-2 increased risk of HIV-1 acquisition among placebo recipients; (unadjusted) uHR=2.2 [95%CI: 1.1-4.2]; (adjusted) aHR=3.5 [1.7-7.1], controlling for male circumcision (MC), region, age, baseline Ad5 serum antibody titer (≤18,>18) and risk behavior. Among all participants we noted uHR=1.7 [1.1-2.7]; aHR=2.3 [1.5-3.7] controlling for vaccine, MC, region, age, Ad5, risk behavior and vaccine-circumcision interaction. Controlling for HSV-2 did not change the vaccine effect among uncircumcised men (aHR=3.27 [1.39-7.68] compared with HR=2.65 [1.18-5.97]). No significant vaccine-HSV-2 interaction was found. No difference in pre-ART VL or time to ART initiation by HSV-2 serostatus was observed.
Conclusions: Baseline HSV-2 seropositivity was associated with a 2-3 fold increased risk of HIV acquisition. Adjusting for HSV-2 did not account for the higher HIV-1 acquisition rate observed in the vaccine group in the primary analysis.
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