Genital Herpes and Human Immunodeficiency Virus: Double Trouble
Celum, Connie, Levine, Ruth, Weaver, Marcia, Wald, Anna, Bulletin of the World Health Organization
Herpes simplex virus type 2 (HSV-2), is a sexually transmitted infection (STI) that is chronic, widespread, and infectious during both its symptomatic and asymptomatic periods. This infection is a significant factor for increased risk of acquisition and transmission of HIV. A meta-analysis of studies on HSV-2 found that infection with HSV-2 doubled the risk of becoming infected with HIV through transmission during sexual activity (1). Furthermore, HSV-2 is the leading cause of genital ulcer disease worldwide. New prevention strategies are urgently needed to reduce the contribution of HSV-2 to HIV transmission, particularly in developing countries that have high prevalence of both HSV-2 and HIV.
The existence of a synergistic relationship between HSV-2 and transmission of HIV has been indicated by many observational and biological studies in which HSV-2 has been implicated as a cofactor in the acquisition and transmission of HIV. HSV-2 causes ulcers and micro-ulcerations, which are often asymptomatic and thus unrecognized; these breaks in the mucosa and the skin in the genital area create portals for the entry of HIV. HSV-2 lesions contain substantial numbers of CD4+ lymphocytes, which are target cells for HIV. Laboratory studies have shown that these CD4+ lymphocytes are likely to facilitate the acquisition of HIV in HIV-negative, HSV-2-positive individuals when they are exposed to HIV. Episodes of reactivation of HSV-2 are associated with increased shedding of HIV from lesions and genital mucosa.
Researchers who have conducted epidemiological and clinical studies on HSV and HIV have proposed that interventions that target HSV-2 infection would provide a way to intervene in transmission of both HIV and HSV-2. Until very recently, most sexually transmitted disease (STD) interventions have focused on bacterial STIs, which are easier to diagnose and treat than genital herpes. As a result, little attention has been paid to the diagnosis of genital herpes and there has been a lack of prevention interventions; consequently, the epidemics of HSV-2 and HIV continue to fuel each other. In some parts of sub-Saharan Africa, where HIV is of great concern, the prevalence of HSV-2 among women is as high as 75% (2).
Recently, large-scale, proof-of-concept, intervention trials have been launched at several sites to determine whether susceptibility to and infectiousness of HIV can be reduced either by treating HSV-2 episodically or by suppressing HSV-2 reactivation. Although there is no cure for genital herpes, the drugs acyclovir, valacyclovir and famciclovir can shorten initial or recurrent episodes ("episodic" therapy). These drugs may also be taken daily for suppression of herpes, which dramatically reduces the frequency and severity of recurrences of HSV-2 ("suppressive" therapy). Support for the concept that antiviral suppression can interrupt transmission of HSV-2 was provided by the results of a recent multi-country, randomized, double-blind study by Corey et al. who found that suppressive therapy with valacyclovir reduced transmission of HSV-2 by 50% for both men and women in heterosexual HSV-2-discordant couples (3).
It is not yet clear which strategy for the diagnosis and management of HSV-2 will be the most feasible and effective in developing countries. The options range from widespread screening for HSV-2 and suppressive antiviral therapy, to other strategies that may have benefits in reducing HSV-2 transmission as well as in HIV prevention. Studies currently being conducted will provide more data on which policy-makers can base their decisions as to the most feasible and cost-effective approaches. Additionally, WHO has incorporated empirical treatment for HSV-2 into irs management recommendations for the syndromic management of genital ulcer disease (4). The impetus for such a significant change in treatment approaches has come from the accumulation of recent research findings and the high prevalence of HSV-2 in many countries. …