This study is designed to determine whether 6 months of anti-HIV drugs given along with tuberculosis treatment will delay the onset of AIDS in HIV infected African patients.

Condition	Treatment or Intervention	Phase
HIV Infections Tuberculosis	Drug: abacavir  Drug: lamivudine  Drug: zidovudine	Phase III

Tuberculosis (TB) is a common and serious complication of HIV infection in the developing world, especially in sub-Saharan Africa. Since the emergence of the HIV epidemic in Africa, the incidence rates of TB have risen dramatically, overwhelming national TB control programs across the continent. Over 50% of TB patients presenting to TB clinics in Africa are HIV infected. These patients often present in the early stages of HIV infection.

Recent World Health Organization guidelines on the management of HIV-associated pulmonary TB recommend antiretroviral (ARV) therapy in patients with CD4 cells less than 200 cells/mm3, but not for HIV infected TB patients who present with a high CD4 count. In Uganda, over half of HIV infected patients with active TB present to TB clinics with CD4 counts above 200 cells/mm3, and there is evidence that coinfected patients with a high CD4 count should be treated with ARV therapy. First, mortality in HIV-associated TB is high, even when patients respond to effective anti-tuberculosis therapy. Second, excess mortality associated with TB is most evident when CD4 counts are above 200 cell/mm3. Third, in coinfected patients, TB results in prolonged immune activation, which may enhance viral replication and accelerate the decline of CD4 cells.

This study will evaluate whether short-term ARV therapy given during treatment of active TB will slow progression of HIV disease in TB patients with CD4 counts of at least 350 cells/mm3. The study will also assess the possible risks (e.g., drug toxicities and resistance) and benefits (e.g., more rapid clearance of mycobacterium tuberculosis and reduced TB relapse) of punctuated ARV therapy.

Participants in this study will be HIV infected TB patients with CD4 counts of at least 350 cells/mm3. All participants will receive treatment for TB. Participants will be randomly assigned to receive 6 months of ARV therapy or to delay ARV therapy until CD4 counts drop below 200 cells/mm3. The participants will be followed for 2 years; CD4 counts will be compared between groups.

This study will also follow a group of HIV infected patients without active TB to quantify the extent to which CD4 cell decline is accelerated with active TB and to determine the extent to which a decline is neutralized in patients who receive punctuated ARV therapy.

Ages Eligible for Study:  13 Years   -   60 Years,  Genders Eligible for Study:  Both

Criteria

Inclusion Criteria

• Diagnosis of pulmonary TB (AFB Smear-positive or culture-positive)
• HIV infected
• CD4 count > 350 cells/mm3
• Residence within 20 km of Kampala
• Two contraceptive methods, including a barrier method, for women of child-bearing potential
• Informed consent for study participation

Christopher Whalen, MD       ccw@case.edu

Uganda
      Makerere University Medical School, Kampala,  Uganda

Study chairs or principal investigators

Christopher C Whalen, MD,  Principal Investigator,  Case Western Reserve University   
Roy Mugerwa, MD,  Principal Investigator,  Makerere University Medical School   
Diane Havlir, MD,  Principal Investigator,  University of California, San Francisco   

Study ID Numbers:  1 R01 AI051219-01A2
Record last reviewed:  February 2004
Record first received:  February 20, 2004
ClinicalTrials.gov Identifier:  NCT00078247
Health Authority: United States: Federal Government
ClinicalTrials.gov processed this record on 2004-10-20