Antiretroviral Therapy for Advanced HIV Disease in South Africa
Condition: HIV
MeSH terms: Acquired Immunodeficiency Syndrome; HIV Infections
Intervention: Zidovudine; Stavudine; Didanosine; Lamivudine; Efavirenz; Lopinavir/Ritonavir
Intervention description: 600 mg once daily; 40 mg once daily; <60 kg/125 mg twice daily or >60kg/200 mg twice daily; 300 mg once daily; 600 mg once daily; r/LPV 400mg/100mg twice daily
Intervention MeSH terms: Ritonavir; Lopinavir; Lamivudine; Zidovudine; Stavudine; Didanosine; Efavirenz
Phase: Phase 4
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Factorial Assignment
Masking: None (Open Label)
Enrollment: 1771.0
Sex: All
Minimum age: 14 Years
Healthy volunteers: No
Keywords: Protease Inhibitors; Reverse Transcriptase Inhibitors; AIDS; Opportunistic Infections; Resource-Poor

Summary:

      This study will determine how well four different antiretroviral drug therapies work in
      patients with advanced HIV disease. The trial is part of the South Africa-U.S. Project
      Phidisa Programme - a collaboration between the South African Military Health Service (SAMHS)
      of the South African National Defense Force (SANDF), the U.S. Department of Defense, and the
      U.S. National Institutes of Health - to help prevent HIV transmission among South African
      military and civilian employees and their families.

      Members of the SANDF with HIV infection may be eligible for this study. HIV-infected family
      members who are 14 years of age and older may also participate. All participants must have a
      CD4 count of less than 200 or an AIDS-defining illness.

      Participants are randomly assigned to one of the following four antiretroviral drug regimens,
      which require taking 5 pills or more every day:

        -  AZT (zidovudine) + ddl (didanosine) + EFV (efavirenz)

        -  AZT (zidovudine) + ddl (didanosine) + r/LPV (lopinavir/ritonavir)

        -  D4T (stavudine) + 3TC (lamivudine) + EFV (efavirenz)

        -  D4T (stavudine) + 3TC (lamivudine) + r/LPV (lopinavir/ritonavir)

      Patients are followed for up to 6 years. Clinic visits are scheduled once a month for the
      first 3 months and then once every 3 months for the next five years. Patients undergo a
      medical history, physical examination, and blood tests at each visit, and complete
      questionnaires of behavior, quality of life, and force readiness every year.
    

Eligibility criteria:

        -  INCLUSION CRITERIA:

        Uniformed SANDF personnel or family members of SANDF personnel who are registered as
        eligible for health services from the SAMHS.

        HIV positive as diagnosed and/or confirmed in PHIDISA I OR documented HIV infection from an
        accredited source.

        CD4+ cell count less than 200 cells/microL (or less than or equal to 14% for patients
        post-splenectomy) AND/OR any AIDS defining illness currently or historically. Patients with
        pulmonary tuberculosis must have a CD4+ cell count less than 200 cells/microL. Patients
        with KS must have a CD4+ cell count less than 200 cells/microL unless their sarcoma is
        progressive and/or requires chemotherapy.

        Antiretroviral treatment naive (less than 7 days cumulative exposure to any antiretroviral
        drug) or treated for post-exposure prophylaxis without becoming HIV infected at that time.

        Laboratory variables as follows:

          1. Haemoglobin greater than or equal to 9.0g/dL for men and greater than or equal to
             8.0g/dL for women.

          2. Absolute neutrophil count greater than or equal to 500 cells/microL.

          3. Platelet count greater than or equal to 25,000/mm(3).

          4. Serum transaminase (ALT or AST) less than or equal to 5 times upper limit of normal
             (ULN).

             14 years or older.

             Likely to be compliant with study procedures and clinical visits in the opinion of the
             clinical investigator (guidance is provided in the protocol to assist clinicians in
             making this decision).

             Have completed the PHIDISA treatment adherence counseling session.

             Provision of written informed consent.

             EXCLUSION CRITERIA:

             Any history of pancreatitis or serious pathology indicative of increased risk for
             pancreatitis.

             Current requirement for use of a medication that is contra-indicated with the PHIDISA
             II study drugs. Where possible, alternate therapies should be selected in order to
             facilitate randomization. Patients entering the study with tuberculosis should defer
             screening and randomization until successful completion of an induction course of
             anti-mycobacterium therapy including rifampicin. As appropriate this patient could
             recommence screening when starting the maintenance regimen of anti-tubercular drugs
             excluding rifampicin.

             Pregnancy (following delivery, such women may be enrolled).