Effect of HSV-2 Suppressive Therapy on Genital Tract HIV-1 RNA Shedding among Women on HAART: A Pilot Randomized Controlled Trial

A E Nijhawan,J Ingersoll,J Kurpewski,S Chapman,A M Caliendo,A Rana,S Cu-Uvin,A K Delong

doi:10.1155/2012/868526

Abstract

Background. The role of suppressive HSV therapy in women coinfected with HSV-2 and HIV-1 taking highly active antiretroviral therapy (HAART) is unclear. Methods. 60 women with HIV-1/HSV-2 coinfection on HAART with plasma HIV-1 viral load (PVL) ≤75 copies/mL were randomized to receive acyclovir (N = 30) or no acyclovir (N = 30). PVL, genital tract (GT) HIV-1, and GT HSV were measured every 4 weeks for one year. Results. Detection of GT HIV-1 was not significantly different in the two arms (OR 1.23, P = 0.67), although this pilot study was underpowered to detect this difference. When PVL was undetectable, the odds of detecting GT HIV were 0.4 times smaller in the acyclovir arm than in the control arm, though this was not statistically significant (P = 0.07). The odds of detecting GT HSV DNA in women receiving acyclovir were significantly lower than in women in the control group, OR 0.38, P < 0.05. Conclusions. Chronic suppressive therapy with acyclovir in HIV-1/HSV-2-positive women on HAART significantly reduces asymptomatic GT HSV shedding, though not GT HIV shedding or PVL. PVL was strongly associated with GT HIV shedding, reinforcing the importance of HAART in decreasing HIV sexual transmission.

Highlights

Herpes simplex virus type 2 (HSV-2) is the most common cause of genital ulcer disease worldwide and has a seroprevalence of 60 to 90% in populations with human immunodeficiency virus type 1 (HIV-1) infection [1]
In persons who are co-infected with HIV-1 and HSV-2, symptomatic and asymptomatic reactivation of HSV-2 has been associated with increased HIV-1 levels in plasma and the genital tract (GT) [2,3,4]
Detection of HSV was significantly associated with reported two-week non-adherence to acyclovir. In this pilot randomized controlled trial study of 60 women, chronic suppressive therapy with acyclovir in HIV-1/HSV-2 positive women on highly active antiretroviral therapy (HAART) was not found to significantly reduce HIV shedding in the genital tract

Summary

Introduction

Herpes simplex virus type 2 (HSV-2) is the most common cause of genital ulcer disease worldwide and has a seroprevalence of 60 to 90% in populations with human immunodeficiency virus type 1 (HIV-1) infection [1]. In persons who are co-infected with HIV-1 and HSV-2, symptomatic and asymptomatic reactivation of HSV-2 has been associated with increased HIV-1 levels in plasma and the genital tract (GT) [2,3,4]. Plasma and genital tract levels of HIV-1 have been shown to significantly decrease with administration of HSV suppressive therapy, [5,6,7] though the role for HSV suppression in the prevention of HIV transmission is unclear. The majority of studies examining the role of HSV suppression in HIV-infected individuals have been conducted in resource-limited settings in individuals not receiving highly active antiretroviral therapy (HAART). Chronic suppressive therapy with acyclovir in HIV-1/HSV-2-positive women on HAART significantly reduces asymptomatic GT HSV shedding, though not GT HIV shedding or PVL. PVL was strongly associated with GT HIV shedding, reinforcing the importance of HAART in decreasing HIV sexual transmission

Methods

Results

Conclusion