The Effects of Herpes Simplex Virus-2 on HIV-1 Acquisition and Transmission: A Review of Two Overlapping Epidemics

Abstract

Increasing evidence demonstrates a substantial link between the epidemics of sexually transmitted HIV-1 and herpes simplex virus (HSV)-2 infection. More than 30 epidemiologic studies have demonstrated that prevalent HSV-2 is associated with a 2- to 4-fold increased risk of HIV-1 acquisition. Per-sexual contact transmission rates among couples from Rakai, Uganda indicate that at all levels of plasma HIV-1 RNA in the source partner, HSV-2-seropositive HIV-1-susceptible persons have a 5-fold greater risk of acquiring HIV-1 compared with HSV-2-negative persons. In vitro and in vivo studies suggest that mucosal HIV-1 shedding is more frequent and in greater amounts during mucocutaneous HSV-2 replication, including subclinical mucosal reactivations. Most HIV-1-infected persons are coinfected with HSV-2, and most experience frequent subclinical and clinical reactivations of HSV-2. Subclinical HSV reactivation elevates serum HIV-1 RNA levels, and daily therapy with acyclovir appears to reduce plasma HIV-1 RNA. These data show that greater attention to the diagnosis and treatment of HSV-2 among HIV-1-infected persons is warranted, especially those who continue to be sexually active, those not on antiretroviral therapy, or those whose disease is not well suppressed by antiretrovirals.

Population Levels of Psychological Stress, Herpesvirus Reactivation and HIV

“…Stress-related reactivation of HSV-2 and EBV may impact risk of HIV acquisition in several ways, including increased occurrence of HSV-2 related genital ulcer disease (GUD), enhancement of HIV-1 replication by infection with HSV-2 and/or EBV, transactivation of HIV-1 by EBV, and CD4 receptor binding similarities with EBV (Carbonari et al 1989;Corey et al 2004;Klatzmann et al 1984;Lin 1993;Scala et al 1993). Indeed, both epidemiological and laboratory findings support a role for ongoing HSV-2 reactivation as a risk factor for HIV-1 acquisition (Corey et al 2004).…”

“…Indeed, both epidemiological and laboratory findings support a role for ongoing HSV-2 reactivation as a risk factor for HIV-1 acquisition (Corey et al 2004). In a large review of epidemiological studies, Corey et al (2004) found a significant risk of HIV acquisition among individuals infected with HSV-2 in cohort, case-control and cross-sectional studies (Corey et al 2004).…”

Gynecologic issues in the HIV-infected woman

“…The treatment of HSV infections in HIV-infected patients is the same as in non-infected patients for episodic infections, and is only slightly modified to include higher doses for recurrent or suppressive therapy. Long term use of acyclovir as suppressive therapy for up to 10 years in HIV-infected individuals is both effective and safe (223), and demonstrates no significant interactions with antiretrovirals (225). If a herpetic lesion persists in an HIVinfected patient on antiviral therapy, HSV resistance should be suspected and appropriate testing should be performed.…”

“…Since acyclovir-resistant strains are usually not susceptible to valacyclovir or famciclovir, intravenous foscarnet should be used for treatment (221). HAART has been shown to reduce the incidence of herpetic ulcers, but it may not affect asymptomatic viral shedding (225). Because HSV-2 coinfection increases the chance of HIV transmission to seronegative partners, and because HSV-2 reactivation causes an elevation in HIV-RNA, there is some data to support serologic testing for HSV-2 in asymptomatic HIV-infected women, with chronic suppressive therapy in those demonstrating HSV-2 antibodies (225).…”

An HSV-1 gD mutant virus as an entry-impaired live virus vaccine

“…Herpes genitalis is a sexually transmitted infection caused primarily by HSV-2, although in some countries the proportion of genital ulcer disease caused by HSV-1 is rising [8][9][10][11]. Herpes genitalis infection increases the risk of acquiring HIV during sexual intercourse by 2-to 4-fold, while HSV-2 infection increases HIV viral load, possibly contributing to higher rates of HIV transmission and disease progression [12].…”