An article published Online First and in an upcoming edition of The Lancet reports that recent research indicates that aciclovir, used to treat HSV2, could delay HIV-1 disease progression in patients co-infected with both conditions. In most cases, people who are infected with HIV-1 are dually infected with herpes simplex virus type 2 (HSV2). The article is the work of Dr Jairam Lingappa, University of Washington, Seattle, WA, USA, and colleagues in Africa and internationally.

It is established that daily suppression of the herpes virus reduces plasma HIV-1 concentrations. However, it is unclear if it delays HIV-1 disease progression. The authors investigated in this study the suppression of herpes simplex virus type 2 with acyclovir. In order to assess the efficacy of suppressive aciclovir on measures of HIV-1 disease progression, they studied African participants who were dually infected with HIV-1 and HSV2.

Fourteen sites in southern and east Africa were included in the trial. A total of 3,381 heterosexual people were recruited. They were all dually infected with HSV2 and HIV-1. Patients were randomly assigned in a 1:1 ratio to aciclovir 400 mg orally twice daily or placebo. They were monitored for up to twenty four months. Eligible participants had CD4 cell counts of 250 cells per μL or higher. In addition, none were taking antiretroviral therapy. Both patients and investigators were unaware of who was receiving which treatment. Effect of aciclovir on HIV-1 disease progression was defined by a combined primary endpoint of first occurrence of CD4 cell count of fewer than 200 cells per μL, antiretroviral therapy initiation, or non-trauma-related death. The researchers also assessed the endpoint of CD4 count falling to

The authors write in conclusion: “We have shown that aciclovir for herpes simplex virus type 2 suppression in people dually infected with HIV-1 and herpes type 2 with CD4 cell counts higher than 250 cells per μL who are not taking antiretroviral therapy can modestly reduce risk of HIV-1 disease progression. Further investigation is needed to establish if suppression of this herpes virus has a role in HIV-1 treatment for people not eligible for antiretroviral therapy.”

Dr Lingappa comments: “While the HIV disease ameliorating effect we have observed is modest, it could add one more tool to help people with HIV infection stay healthy for longer.”

In an associated note, Dr Anne Buvé and Dr Lutgarde Lynen, Institute of Tropical Medicine, Antwerp, Belgium, comment: “Further research is needed on the feasibility and cost- effectiveness of suppressive therapy for infection with HSV2 as a strategy to slow disease progression in HIV co-infected patients. In the meantime, efforts should be stepped up to ensure that HIV-infected patients in low-income and middle-income countries who have frequent recurrences of genital herpes or severe genital herpes receive suppressive therapy with aciclovir, as recommended in industrialised countries.”

“Daily aciclovir for HIV-1 disease progression in people dually infected with HIV-1 and herpes simplex virus type 2 a randomised placebo-controlled trial”
Jairam R Lingappa, Jared M Baeten, Anna Wald, James P Hughes, Katherine K Thomas, Andrew Mujugira, Nelly Mugo, Elizabeth A Bukusi, Craig R Cohen, Elly Katabira, Allan Ronald, James Kiarie, Carey Farquhar, Grace John Stewart, Joseph Makhema, Myron Essex, Edwin Were,Kenneth H Fife, Guy de Bruyn, Glenda E Gray, James A McIntyre, Rachel Manongi, Saidi Kapiga, David Coetzee, Susan Allen, Mubiana Inambao,Kayitesi Kayitenkore, Etienne Karita, William Kanweka, Sinead Delany, Helen Rees, Bellington Vwalika, Amalia S Magaret, Richard S Wang,Lara Kidoguchi, Linda Barnes, Renee Ridzon, Lawrence Corey, Connie Celum, for the Partners in Prevention HSV/HIV Transmission Study Team
DOI: 10.1016/S0140-6736(09)62038-9
The Lancet

Written by Stephanie Brunner (B.A.)