 Interventions that slow HIV-1 disease progression among persons with CD4 counts above 250 cellsmicroliter could postpone the need for antiretroviral therapy ART and prolong life-expectancy for HIV-infected persons. Herpes simplex virus type 2 HSV-2 has been shown to up-regulate HIV-1 replication at the cellular level. 1 This finding has been supported by clinical evidence that individuals who are HSV-2 seropositive at the time of HIV-1 seroconversion had higher HIV viral loads at 5 and 15 months post-seroconversion. 2 Earlier studies during the era of zidovudine Retrovir monotherapy showed a survival advantage when acyclovir ACV, Zovirax was added to the treatment of patients with HIV. 3 Acyclovir prophylaxis has been shown to decrease herpes simplex virus infections and varicella-zoster virus infections among HIV infected patients in a meta-analysis of randomized trials from North America and Europe. This analysis also found a reduced risk of mortality among patients treated with acyclovir. The potential of acyclovir to slow HIV-1 disease progression has not been assessed in a randomized trial in Africa where high rates of HSV-2 infection have been observed among HIV-1 infected individuals. This study proposes to assess the benefits of acyclovir prophylaxis among HIV-1 infected individuals dually infected with HSV-2 who are not on ART through a randomized double-blind placebo controlled trial. 