"We know that proteins in the herpes virus can upregulate HIV transcription," said principal investigator Richard Zuckerman, MD, MPH, director, transplant infectious diseases, section of infectious disease and international health, Dartmouth-Hitchcock Medical Center, Lebanon, New Hampshire. "As a correlate to that, we wanted to see if by giving valacyclovir, if it would make a difference in patients' HIV-1 levels."

In his late breaker poster presentation, Dr. Zuckerman noted that most patients infected with HIV also are infected with HSV-2 (JAIDS 2004). Moreover, 2 studies suggested HSV-2 infection elevates the risk of acquiring and transmitting HIV (JID 2002; Lancet 2001).

In their randomized, double-blinded, placebo-controlled, crossover trial, Dr. Zuckerman and colleagues enrolled 20 men who reported having sex with men. Their median age was 31 years and half of them had a history of anal or genital herpes, symptomatic genital herpes during the trial, or prior herpes antiviral medication use.

Patients had both HIV-1 and HSV-2, had a CD4 count exceeding 200 cells/mm³, were at least 18 years old, and had never been treated with antiretroviral therapy.

Ten patients received oral valacyclovir 500 mg twice daily for 8 weeks and 10 received placebo, followed by a 2-week washout period. Patients who initially got placebo were then given valacyclovir for 8 weeks, and patients who initially got valacyclovir were given placebo.

Subjects collected daily anogenital swabs for samples of HSV DNA, and anoscopy was performed 3 times weekly to provide rectal HIV-1 RNA and HSV DNA samples. Blood plasma was collected weekly to provide HIV-1 RNA samples. Investigators then measured plasma and rectal HIV-1 RNA levels in each group.

Investigators found that HSV suppressive therapy decreased plasma HIV-1 levels by 53%, with an average reduction of 0.33 log₁₀ copies/mL. The therapy reduced rectal HIV-1 levels by 31%, with an average decrease of 0.16 log₁₀ copies/mL.

Valacyclovir had an enhanced impact on decreasing plasma HIV-1 levels in men with higher CD4 counts (P = .018).

"We need to do further work to see the long-term effect on HIV levels and transmission with HSV suppression," Dr. Zuckerman said.

The study was supported by a research grant from GlaxoSmithKline and the National Institutes of Health in the U.S.


[Presentation title: HSV Suppression With Valacyclovir Reduces Blood Plasma and Rectal HIV-1 Levels in HIV-1, HSV-2 Seropositive Men. Poster LB-25]

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