Acyclovir to Treat Patients Co-infected With HIV and Herpes Viruses in Uganda
Condition: HIV Infections; Herpes Genitalis
MeSH terms: Herpes Genitalis
Intervention: Acyclovir; Placebo
Intervention description: 400mg twice daily for 24 months; Placebo tablet twice daily for 24 months
Intervention MeSH terms: Acyclovir
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Enrollment: 440.0
Sex: All
Minimum age: 18 Years
Maximum age: 65 Years
Healthy volunteers: No
Keywords: AIDS; HIV Disease Progression; Quality of Life; HIV Viral Load; Genital Ulcers; HIV; Treatment Naive

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.
    

Eligibility criteria:

        -  INCLUSION CRITERIA:

               1. Documentation of HIV-1 infection, by either two positive ELISAs or two discrepant
                  ELISAs with a confirmatory positive Western Blot

               2. Documentation of prior HSV-2 infection by Focus Kalon ELISA

               3. Absolute CD4+ T-cell count of greater than or equal to 300 and less than or equal
                  to 400 cells/microliter within 30 days prior to randomization

               4. All participants must be receiving Cotrimoxazole prophylaxis as part of standard
                  care unless contraindicated

               5. Age at least 18 years and above

               6. Laboratory values (within 30 days prior to randomization)

                    1. Aspartate transaminase (AST) no more than five times the upper limit of
                       normal (ULN)

                    2. Total bilirubin no more than 2 times ULN

                    3. Creatinine no more than 2.0 mg/dL

                    4. Platelet count at least 50 000/microliter

                    5. Hemoglobin at least 8g/dL

               7. Written informed consent

        EXCLUSION CRITERIA:

          1. Concurrent malignancy or any other disease state requiring cytotoxic chemotherapy

          2. Symptomatic for significant HIV-related illnesses (WHO stage III or IV), such as
             opportunistic infections and malignancies other than mucocutaneous Kaposi's sarcoma. A
             history of AIDS defining opportunistic infections other than mucocutaneous Kaposi's
             sarcoma or candida or treated tuberculosis

          3. Active HSV-2 disease as suggested by painful genital ulcer disease at time of
             screening or enrollment

          4. Current use of antiretroviral medications or Preventing Mother-to-Child Transmission
             (PMTCT) use of antiretrovirals within the previous 6 months

          5. Significant cardiac, pulmonary, kidney, rheumatologic, gastrointestinal, or CNS
             disease as detectable on routine medical history, physical examination, or screening
             laboratory studies.

          6. Psychiatric illness that, in the opinion of the PI, might interfere with the study
             compliance.

          7. Active substance abuse or history of prior substance abuse that may interfere with
             protocol compliance or patient safety.

          8. CD4+ count less than 300 or more than 400 cells/microliter.