Emma Hitt, PhD

July 20, 2011

July 20, 2009 (Rome, Italy) — Patients coinfected with HIV and herpes simplex virus (HSV)-2 have slower progression of HIV if they take daily acyclovir. In a study conducted in Rakai, Uganda, acyclovir was found to reduce the rate of disease progression by 27%.

Steven J. Reynolds, MD, MPH, from thedivision of infectious diseases at Johns Hopkins University School of Medicine, in Baltimore, Maryland, presented the findings during an oral session here at the 6th International AIDS Society Conference on HIV Pathogenesis, Treatment and Prevention.

According to the researchers, daily suppression of HSV-2 reduces plasma HIV-1 concentrations and has been shown to delay HIV-1 disease progression modestly in previous studies.

"One recent report of results from 7 randomized controlled trials suggested that daily acyclovir or valacyclovir reduced plasma HIV-1 by 0.33 log10 copies/mL" (95% confidence interval [CI], –0.56 to –0.10), Dr. Reynolds said during his presentation.

The current study sought to investigate the impact of daily suppressive acyclovir on HIV-1 disease progression in a cohort of 440 dually infected patients in Rakai.

All participants were adults with CD4 T-cell counts between 300 and 400 cells/µL and were not receiving antiretroviral therapy (ART) because they were not yet eligible according to local guidelines.

Patients were randomized in a 1:1 fashion to receive either acyclovir 400 mg orally twice daily or placebo, and were then followed for 2 years. The primary outcome was a CD4 count below 250 cells/µL or initiation of ART for World Health Organization stage IV AIDS disease.

Overall, 110 participants in the placebo group and 95 in the treatment group reached the primary end point (hazard ratio [HR], 0.73; 95% CI, 0.56 to 0.97; P = .029), representing a significant 27% reduction in patients receiving acyclovir in terms of the proportion reaching progression of HIV.

The researchers calculated that adherence was high in both study groups; 81% to 95% of participants achieved more than 90% study drug coverage.

The benefits of acyclovir therapy were especially pronounced for patients with a higher viral load at the start of the study. The 2 highest viral-load quintiles were shown to have the strongest effect of treatment (HR, 0.64; 95% CI, 0.43 to 0.96; P = .03), whereas the 2 lowest viral-load quintiles showed no efficacy (HR, 0.90; 95% CI, 0.54 to 1.50; P = .688).

According to Dr. Reynolds, HSV-2 is the most common cause of genital ulcer disease, and HSV-2 seroprevalence rates are 70% to 90% among HIV-1 infected individuals. "HSV-2 reactivation is common and known to increase HIV-1 replication," he told Medscape Medical News.

"Despite the enormous success of ART scale-up, vast numbers of HIV-infected individuals in resource-limited settings are not yet on antiretroviral [treatment], either because of a lack of access or because they have not yet reached eligibility criteria yet," he said.

"Strategies to delay HIV disease progression could offset some of the burden faced by countries continuing to scale up treatment with limited resources," he said. "Treatment of chronic HSV-2 infection may be warranted in HIV-infected individuals," he added.

According to Dr. Reynolds, future studies of valacyclovir, which has better bioavailability than acyclovir, are warranted; it may have an even greater impact on HIV disease progression.

"It is great to see these findings replicated in a second cohort of patients, underscoring, for clinicians, the fact that acyclovir, an extremely safe drug, can have added benefits for individuals dually infected with HSV-2 and HIV-1," said independent commentator Jairam Lingappa, MD, associate professor in the Departments of Global Health and Medicine and adjunct associate professor in the Department of Pediatrics at the University of Washington, Seattle. Dr. Lingappa was previously a medical epidemiologist at the US Centers for Disease Control and Prevention.

"Further study is needed to determine how HSV-2 suppression should be integrated with antiretroviral drug treatment," he told Medscape Medical News. "This is particularly important in light of recent findings suggesting a benefit of initiating antiretroviral treatment in individuals with higher CD4 counts," he added.

The study was not commercially funded. Dr. Reynolds and Dr. Lingappa have disclosed no relevant financial relationships.

6th International AIDS Society (IAS) Conference on HIV Pathogenesis, Treatment and Prevention: Abstract TUAB0104. Presented July 19, 2011.


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