Acyclovir to Treat Patients Co-infected With HIV and Herpes Viruses in Uganda
Condition: HIV Infections; Herpes Genitalis
MeSH terms: Herpes Genitalis
Study type: Interventional
Phase: Phase 2

Summary: 
      This study will determine whether acyclovir, a medicine used to treat herpes simplex virus 2
      (HSV-2), can slow down the progression (worsening) of HIV disease in people with both HIV and
      HSV-2 infections. HSV-2 increases the amount of HIV virus in the blood of infected people and
      may make HIV progress faster. The study will evaluate:

      "Whether people who take acyclovir can avoid antiretroviral treatment until later in their
      lives

      "Whether people who take acyclovir get fewer genital ulcers

      "How well people are able to take acyclovir and any side effects they experience from it

      "Differences in the amount of HIV virus in the blood of patients who are and are not taking
      acyclovir, and how HIV/AIDS is different in these patients.

      People 18 years of age and older living in the Rakai district of Uganda who are infected with
      both HIV (early stage disease) and HSV-2 may be eligible for this study. Participants are
      randomly assigned to take the study drug, acyclovir, or a placebo (look-alike pill with no
      active ingredient) daily for 2 years. During this time, they visit the clinic once a month
      for a routine physical examination. Patients who develop genital ulcers or complications of
      HIV are treated for the problem, and patients whose HIV disease progresses, requiring them to
      begin antiretroviral therapy, are treated accordingly.
    

Detailed description: 
      Interventions that slow HIV-1 disease progression among persons with CD4+ counts above 250
      cells/microliter 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.
    

Intervention name(s): Acyclovir; Placebo
Intervention type(s): Drug; Drug
Intervention description(s): 400mg twice daily for 24 months; Placebo tablet twice daily for 24 months
Intervention MeSH terms: Acyclovir
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary purpose: Treatment
Keywords: AIDS; HIV Disease Progression; Quality of Life; HIV Viral Load; Genital Ulcers; HIV; Treatment Naive