Abstract
BackgroundCo-infection with herpes simplex virus type 2 (HSV-2) has been associated with increased HIV-1 RNA levels and immune activation, two predictors of HIV-1 progression. The impact of HSV-2 on clinical outcomes among HIV-1 infected pregnant women is unclear.MethodsHIV-1 infected pregnant women in Nairobi were enrolled antenatally and HSV-2 serology was obtained. HIV-1 RNA and CD4 count were serially measured for 12–24 months postpartum. Survival analysis using endpoints of death, opportunistic infection (OI), and CD4<200 cells µL, and linear mixed models estimating rate of change of HIV-1 RNA and CD4, were used to determine associations between HSV-2 serostatus and HIV-1 progression.ResultsAmong 296 women, 254 (86%) were HSV-2-seropositive. Only 30 (10%) women had prior or current genital ulcer disease (GUD); median baseline CD4 count was 422 cells µL. Adjusting for baseline CD4, women with GUD were significantly more likely to have incident OIs (adjusted hazard ratio (aHR) 2.79, 95% CI: 1.33–5.85), and there was a trend for association between HSV-2-seropositivity and incident OIs (aHR 3.83, 95% CI: 0.93–15.83). Rate of change in CD4 count and HIV-1 RNA did not differ by HSV-2 status or GUD, despite a trend toward higher baseline HIV-1 RNA in HSV-2-seropositive women (4.73 log10 copies/ml vs. 4.47 log10 copies/ml, P = 0.07).ConclusionsHSV-2 was highly prevalent and pregnant HIV-1 infected women with GUD were significantly more likely to have incident OIs than women without GUD, suggesting that clinically evident HSV-2 is a more important predictor of HIV-1 disease progression than asymptomatic HSV-2.
Highlights
HIV-1 and herpes simplex virus type 2 (HSV-2) co-infection presents important implications during pregnancy for women and their children
A multisite randomized controlled trial of daily acyclovir in over 3,000 HIV1-seropositive, HSV-2-seropositive African adults demonstrated that HSV-2 suppression produced a sustained reduction in HIV-1 viral load over a 2-year period in participants on acyclovir [10], and reduced risk of HIV-1 disease progression events by 16% when compared to placebo [20]
Ten women (3%) were diagnosed with syphilis at baseline; only one woman with serologic syphilis had an observed or reported ulcer; verifying that most genital ulcers in our cohort were due to HSV-2
Summary
HIV-1 and herpes simplex virus type 2 (HSV-2) co-infection presents important implications during pregnancy for women and their children. Prior studies in HIV-1 infected pregnant women have demonstrated associations between HSV-2 and genital ulcers and perinatal HIV-1 transmission [1,2,3,4], and co-infected women have increased genital shedding of HIV-1 [5]. Multiple short randomized trials of acyclovir or valacyclovir in co-infected patients have shown 0.25 to 0.5 log copies/ml reductions in HIV-1 viral load [10,14,15,16,17,18,19]. Co-infection with herpes simplex virus type 2 (HSV-2) has been associated with increased HIV-1 RNA levels and immune activation, two predictors of HIV-1 progression. The impact of HSV-2 on clinical outcomes among HIV-1 infected pregnant women is unclear
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