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Valacyclovir Reduces HIV-1 Levels in Men Coinfected With Herpes Simplex Type 2: Presented at IDSA

By Louise Gagnon

TORONTO, CANADA -- October 17, 2006 -- The use of therapy for herpes simplex virus type 2 (HSV-2) can help reduce plasma and rectal levels of HIV-1 in coinfected men, according to findings presented here at the Infectious Diseases Society of America (IDSA) 44^th Annual Meeting.

"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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