Tuberculosis and Human Immunodeficiency Virus (HIV) Immune Reconstitution Syndrome Trial (THIRST)
Condition: HIV; Tuberculosis
MeSH terms: Tuberculosis; Immune Reconstitution Inflammatory Syndrome
Intervention: Fixed dose combination zidovudine/lamivudine/abacavir
Intervention description: All subjects will receive fixed dose combination zidovudine(300 mg) / lamivudine (150 mg) / abacavir (300 mg) by mouth twice daily. Medications will be provided as long as deemed beneficial by the site investigator and study subject for up to two years. Toxicity substitutions are allowed per protocol.
Intervention MeSH terms: Lamivudine; Zidovudine; Abacavir
Phase: Phase 4
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: None (Open Label)
Enrollment: 70.0
Sex: All
Minimum age: 13 Years
Healthy volunteers: No
Keywords: HIV; Tuberculosis; Treatment Naive

Summary:

      The purpose of this study is twofold: (1) to assess the feasibility and safety of fixed dose
      combination zidovudine/lamivudine/abacavir in HIV infected subjects with tuberculosis in a
      resource-limited setting, and (2) to assess the impact of delayed versus early initiation
      strategies for fixed dose combination zidovudine/lamivudine/abacavir on the rate of
      tuberculosis-associated immune reconstitution inflammatory syndromes.
    

Eligibility criteria:

        Inclusion Criteria:

          -  HIV Infection is documented by rapid HIV test or any licensed enzyme-linked
             immunosorbent assay (ELISA) test kit and confirmed with a different sample.

          -  Men or women admitted to Kibongoto or Marangu Hospitals with (a) recent (within 56
             days) smear positive tuberculosis (pulmonary or extrapulmonary,) (b)total lymphocyte
             count <1,200/mm3, and (c) less than 14 days of antituberculous therapy.

          -  Antiretroviral naive with the exception of regimens used to prevent mother-to-infant
             transmission of HIV during pregnancy.

          -  The following laboratory values obtained within 45 days prior to study entry: absolute
             neutrophil count (ANC) >=700/mm³, hemoglobin > 8 g/dL in women; >9 g/dL in men, serum
             creatinine <= 1.5 times upper limits of normal, AST <5 times upper limits of normal.

          -  For all women of reproductive potential (who have not reached menopause or undergone
             hysterectomy, bilateral oophorectomy, or tubal ligation), a negative urine pregnancy
             test within 48 hours of to study.

          -  All subjects must agree not to participate in a conception process (e.g., active
             attempt to become pregnant or to impregnate) and if participating in sexual activity
             that could lead to pregnancy, the female subject/male partner must use condoms (male
             or female) without a spermicidal agent.

          -  Not intending to relocate out of area for the duration of study participation.

          -  Willingness of subject to adhere to follow up schedule.

          -  Men and women >= age 13.

          -  Ability and willingness of subject or legal guardian/representative to give written
             consent.

        Exclusion Criteria:

          -  Serious illness, other than tuberculosis, that requires systematic treatment and/or
             hospitalization, until either completion of therapy or clinical stability on therapy
             in the opinion of the investigator for at least 14 days prior to study entry. Oral and
             vaginal candidiasis, mucocutaneous herpes simples, and other illnesses which are minor
             in the opinion of the site investigator are exceptions

          -  Diagnosis of or suspicion of tuberculosis of the central nervous system.

          -  > 14 days of antituberculous therapy prior to screening.

          -  > 28 days of antituberculous therapy for active tuberculosis within the 6 months prior
             to screening.

          -  Recent past (within 28 days of study entry) or planned use of corticosteroids.

          -  Any condition that in the opinion of the investigator would compromise the subject's
             ability to participate in the study.

          -  Radiation or systemic chemotherapy within 45 days of entry.

          -  Any immunomodulator, HIV vaccine, or other investigational therapy within 30 days
             prior to study entry.

          -  Active drug or alcohol use or dependence that, in the opinion of the investigator,
             would interfere with adherence to study requirements.

          -  Allergy/sensitivity to any study drugs or their formulations.