Herpes Simplex Virus (HSV) Suppression with Valacyclovir Reduces Rectal and Blood Plasma HIV-1 Levels in HIV-1/HSV-2-Seropositive Men: A Randomized, Double-Blind, Placebo-Controlled Crossover Trial

Section of Infectious Disease and International Health, Dartmouth-Hitchcock Medical Center, Lebanon, NH, USA.
The Journal of Infectious Diseases (Impact Factor: 6). 11/2007; 196(10):1500-8. DOI: 10.1086/522523
Source: PubMed


Herpes simplex virus type 2 (HSV-2) infection is common among human immunodeficiency virus (HIV)-infected persons, and HSV reactivation increases plasma and genital HIV-1 levels. We studied HIV-1 levels during HSV suppression in coinfected persons in a placebo-controlled crossover trial.
Twenty antiretroviral therapy (ART)-naive HIV-1/HSV-2-seropositive men who have sex with men in Lima, Peru, with CD4 cell counts >200 cells/ microL were randomized to receive either valacyclovir at 500 mg twice daily or placebo for 8 weeks, after which they underwent a 2-week washout period and then received the alternative regimen for 8 weeks. Specimens included daily anogenital swabs (for HSV DNA polymerase chain reaction [PCR]), thrice weekly rectal mucosal secretions (for HIV-1 RNA and HSV DNA PCR) obtained by anoscopy, and weekly plasma (for HIV-1 RNA PCR). Outcomes were rectal and plasma HIV-1 RNA levels by treatment arm.
HIV-1 was detected in 73% of 844 rectal and 99% of 288 plasma specimens. HSV was detected in 29% and 4% of mucocutaneous specimens obtained during placebo and valacyclovir administration, respectively (P<.001). Valacyclovir resulted in a 0.16 (95% confidence interval [CI], 0.07-0.25; P=.0008; 33% decrease) log(10) copies/mL lower mean within-subject rectal HIV-1 level and a 0.33 (95% CI, 0.23-0.42; P<.0001; 53% decrease) log(10) copies/mL lower plasma HIV-1 level, compared with values for placebo.
Valacyclovir significantly reduces rectal and plasma HIV-1 levels in HIV-1/HSV-2-coinfected men. HSV suppression may provide clinical benefits to persons not receiving highly active ART as well as public health benefits.

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    ABSTRACT: To assess the long-term effects of population-level HSV-2 infection on HIV incidence. Data from a population-based cohort in south-western Uganda were used to estimate HIV incidence from 1990 to 2007. Stored blood samples were tested for HSV-2, and the impact of HSV-2 prevalence and incidence on HIV incidence was estimated by calculating population attributable fractions (PAFs). The association between population-level annual HIV incidence and annual HSV-2 incidence/prevalence was analysed using linear regression. HIV incidence declined over time among men, from 8.72/1000 person-years (pyr) in 1990 to 4.85/1000 pyr in 2007 (P-trend <0.001). In contrast, there was no decline in HIV incidence among women (4.86/1000 pyr in 1990 to 6.74/1000 pyr in 2007, P-trend = 0.18). PAFs of incident HIV attributable to HSV-2 were high (60% in males; 70% in females). There was no evidence of an association between long-term trends in HIV incidence and HSV-2 prevalence or incidence. Assuming a causal relationship, a substantial proportion of new HIV infections in this population are attributable to HSV-2. The study did not find an effect of HSV-2 prevalence/incidence on trends in HIV incidence. HIV incidence did not vary much during the study period. This may partly explain the lack of association.
    Tropical Medicine & International Health 10/2013; 18(10):1257-66. DOI:10.1111/tmi.12176 · 2.33 Impact Factor
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    • "Herpes simplex virus (HSV) is known to cause diseases of various severities, including mucocutaneous diseases, neonatal herpes and herpes encephalitis [1]. Recent reports also suggest HSV infection could strongly increase risk for HIV infection [2]. HSV has become one of the most common sexual transmitted diseases in U.S.A., U.K., French and other western societies [3] [4] [5]. "
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    Statistics in Medicine 01/2013; 32(2). DOI:10.1002/sim.5526 · 1.83 Impact Factor
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    • "Recent studies have revealed that abnormal vaginal flora triggers the shedding of HSV and cytomegalovirus (CMV) in women genital tract [11,12]. On the other hand genital herpes infection is a major risk factor for acquisition and transmission of HIV via sexual contact [13,14]. Moreover, HIV copy number in female genital-tract discharge inversely correlates with lactobacilli counts in bacterial flora [15]. "
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    DARU-JOURNAL OF FACULTY OF PHARMACY 10/2012; 20(1):53. DOI:10.1186/2008-2231-20-53 · 1.64 Impact Factor
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