Most people who are infected with HIV-1 are dually infected with herpes simplex virus type 2 (HSV2). New research shows that aciclovir, used to treat HSV2, could delay HIV-1 disease progression in patients co-infected with both conditions. The findings are published in an Article Online First and in an upcoming edition of The Lancet--written by Dr Jairam Lingappa, University of Washington, Seattle, WA, USA, and colleagues both across Africa and globally.
Daily suppression of this herpes virus reduces plasma HIV-1 concentrations, but whether it delays HIV-1 disease progression is unknown. In this study, the authors studied suppression of herpes simplex virus type 2 with aciclovir in African participants who were dually infected with HIV-1 and HSV2 to assess the efficacy of suppressive aciclovir on measures of HIV-1 disease progression.
The trial took place at 14 sites in southern and east Africa, and recruited 3381 heterosexual people who were 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, and were followed up for up to 24 months. Eligible participants had CD4 cell counts of 250 cells per μL or higher and were not taking antiretroviral therapy. Patients and investigators did not know 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 <350 cells per μl.
The researchers found that aciclovir reduced risk of HIV-1 disease progression by 16%; 284 participants assigned aciclovir versus 324 assigned placebo reached the primary endpoint. In those with CD4 counts ≥350 cells per μL, aciclovir reduced the risk of CD4 cell counts falling to <350 cells per μl by 19%.
As recently reported, aciclovir treatment in individuals with genital herpes and HIV in this study population did not reduce HIV transmission to their heterosexual partners. The authors note in this new Lancet report that antiretroviral therapy would likely have a greater effect on reducing HIV-1 disease progression than was seen with aciclovir in this study. However, the current findings suggest that aciclovir may provide an additional option for individuals who have not reached medical thresholds for initiating antiretroviral therapy.
The authors conclude: "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 adds*: "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 accompanying Comment, Dr Anne Buvé and Dr Lutgarde Lynen, Institute of Tropical Medicine, Antwerp, Belgium, say: "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."