HSV Infection in HIV Infected Individuals

Lawrence Corey, MD

This research project is concerned with evaluating the role HSV infection plays in the acquisition and transmission of HIV and in the progression of HIV infection. This project is a subproject of the program project "Clinical Epidemiology and Pathogenesis of Asymptomatic HSV" (PI-Lawrence Corey, MD). The investigators have previously shown that prior HSV-2 infection appears to significantly increase the risk of acquiring HIV-1 in homosexual men who engage in high-risk behavior. In individuals who are infected with both HSV-2 and HIV-1, high titers of HIV-1 RNA are found in active genital herpes lesions. In addition, natural history studies have shown the frequency of clinical and subclinical HSV-2 reactivation to be 2 to 4-fold higher in HIV-positive as compared to HIV-negative persons.

The specific aims are to:

1. Determine if prior HSV-2 infection increases the risk of acquisition of HIV-1 infection by sexual transmission in high-risk heterosexual and homosexual men and women. These studies are being done in collaboration with the NIAID HIVNET sites. The use of the HIVNET program allows the analysis of large numbers of study subjects needed to demonstrate that HSV-2 infection is a primary risk factor predisposing to the acquisition of HIV rather than only a marker for high-risk sexual behavior.
2. Evaluate the effect of subclinical reactivation of HSV on local HIV replication. The investigators have previously demonstrated HIV virions in genital herpes lesions, but most HSV shedding occurs in the absence of lesions, especially in the perianal region. In this specific aim, cervicovaginal secretions, rectal mucosa and semen will be examined to determine if asymptomatic HSV shedding is associated with an increase in HIV titers in these secretions. This study will compare HIV-1 shedding between persons with frequent or infrequent HSV reactivation, and between persons who shed HSV in high titers or low titers.
3. Evaluate the ability of HSV antiviral therapy to (a) suppress HIV shedding from genital herpes lesions and (b) reduce mucosal and systemic levels of HIV load. The investigators have found HIV virions in active herpes lesions and not in intact skin, and HIV RNA disappeared from the genital skin as the lesions resolved. Preliminary work has also shown that daily acyclovir consistently reduced plasma HIV-1 RNA. This first part of this specific aim is exploring the hypothesis that suppression of HSV replication with acyclovir will markedly reduce the presence of HIV-1 in genital lesions. The study is a cross-over comparison of the effect of acyclovir vs. placebo on HIV shedding from genital herpes lesions through two subsequent recurrences in HIV-infected persons. For the second part of this specific aim, the investigators are monitoring the effect of acyclovir on the levels of plasma and mucosal HIV RNA. This study is a cross-over evaluation of the effect of an 8-week treatment regimen with acyclovir on the plasma and mucosal HIV RNA levels in HSV-2 infected patients.
4. Describe the natural history of HSV infection in HIV-positive patients treated with highly active antiretroviral therapy (HAART) and determine if HAART restores the ability of the immune system to contain mucosal HSV replication. This study will be carried out in men receiving HAART treatment. HSV shedding rates in genital secretions are determined before and after administration of combination antiretroviral therapy.

This research project will define many aspects of the role reactivated HSV infection plays in the acquisition, transmission and progression of HIV infection. Moreover, these studies will provide important information that can be used to develop rational, scientifically-based guidelines on managing HSV infection in HIV-positive persons.

Report courtesy of Anna Marie Beckmann

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Recent Publications

Hobson A, Wald A, Wright N, Corey L. Evaluation of a quantitative competitive PCR assay for measuring herpes simplex virus DNA content in genital tract secretions. J Clin Microbiol 1997; 35:548-52.