IAS: Herpes Drug Slows HIV Progress

ROME -- A drug that suppresses herpes simplex-2 (HSV-2) also curtails the progression of HIV, a researcher reported here.
In a randomized controlled trial in Uganda, acyclovir (Zovirax), taken twice a day, increased the time before co-infected participants needed HIV treatment or suffered an AIDS-defining illness, according to Steven Reynolds, MD, of the National Institute of Allergy and Infectious Diseases in Bethesda, Md.

In places where access to antiretroviral drugs is limited, the approach may ease the pressure on treatment resources, Reynolds told a session at the 2011 meeting of the International AIDS Society here.

He added that more research is needed to confirm the findings, but acyclovir treatment "may be warranted" in people with both HIV and HSV-2.

The study enrolled 440 people with both infections and assigned them randomly to get 400 mg of acyclovir twice daily or placebo, Reynolds reported.

Participants had a CD4-positive T-cell count of between 300 and 400 cells per microliter of blood and were not eligible for HIV treatment under Uganda's guidelines.

The goal was to measure the impact of acyclovir over a two-year period on the risk of reaching a level of 250 cells per microliter or fewer, or suffering a World Health Organization stage 4 event, Reynolds said. At either point, therapy would be indicated.

Over the study period, 205 participants reached the primary endpoint, he said -- 95 in the treatment arm and 110 in the placebo arm. Those figures yielded a hazard ratio for progression of 0.73, with a 95% confidence interval from 0.56 to 0.97, which was significant at P=0.029.

Analysis showed the difference was almost entirely driven by people who started the trial with a plasma viral load of greater than 50,000 copies of HIV RNA per ml, Reynolds said.

In that group, the hazard ratio for progression was 0.62, with a 95% confidence interval from 0.43 to 0.96, which was significant at P=0.03. In contrast, among those with a lower viral load, the hazard ratio was a nonsignificant 0.90, Reynolds reported.

The researchers also found that patients on placebo had a rising plasma viral load over time -- an annual average increase of 0.402 log10 copies of HIV RNA per ml -- while those on acyclovir saw their viral load fall by an average of 0.061 log10 copies per ml.

The difference was significant at P=0.001, Reynolds said.

But the study may be missing the point, in the light of recent findings in treatment as HIV prevention, according to Pedro Cahn, MD, of Fundación Huesped in Buenos Aires and a former president of the IAS.

Cahn himself is involved in a study testing a similar drug -- valacyclovir (Valtrex) -- for the same purpose, but he told MedPage Today that such strategies can only have an application as long as it's necessary to delay treatment because resources are scarce.

Cahn and others here are arguing that most resources should be put into expanding access to treatment, rather than using them to delay the medical need for therapy.

In the "big picture," it's now clear that full-scale treatment of people with HIV -- regardless of the stage of their illness -- is the best way to slow and perhaps halt the pandemic, Cahn said.

The researchers have made "very interesting scientific findings," he said. "The issue is what should we do once the scientific questions have been answered."

The study was supported by the NIH and PEPFAR. Reynolds is an employee of the National Institute of Allergy and Infectious Diseases.

Cahn has previously reported financial links with Abbott, Pfizer, GlaxoSmithKline, Pharmacia, and Roche.