Anti-HIV Drugs for Ugandan Patients With HIV and Tuberculosis

NCT ID: NCT00078247

Last Updated: 2010-08-12

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE3
• Total Enrollment: 350 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2004-10-31

Brief Summary

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.

Detailed Description

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 of abacavir sulfate, lamivudine, and zidovudine 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 250 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.

Conditions

HIV Infections; Tuberculosis

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

1

Participants will receive 6 months of ARV therapy and treatment for TB

Group Type: EXPERIMENTAL

Abacavir

Intervention Type: DRUG

300 mg tablet taken orally twice daily

Lamivudine

Intervention Type: DRUG

300 mg tablet taken orally daily

Zidovudine

Intervention Type: DRUG

300 mg tablet taken orally twice daily

Tuberculosis treatment

Intervention Type: DRUG

Tuberculosis treatment

2

Participants will not receive ARV therapy until CD4 counts drop below 250 cells/mm3. All participants will receive treatment for TB.

Group Type: EXPERIMENTAL

Abacavir

Intervention Type: DRUG

300 mg tablet taken orally twice daily

Lamivudine

Intervention Type: DRUG

300 mg tablet taken orally daily

Zidovudine

Intervention Type: DRUG

300 mg tablet taken orally twice daily

Tuberculosis treatment

Intervention Type: DRUG

Tuberculosis treatment

Interventions

Abacavir

300 mg tablet taken orally twice daily

Intervention Type: DRUG

Lamivudine

300 mg tablet taken orally daily

Intervention Type: DRUG

Zidovudine

300 mg tablet taken orally twice daily

Intervention Type: DRUG

Tuberculosis treatment

Tuberculosis treatment

Intervention Type: DRUG

Eligibility Criteria

Inclusion Criteria

• Diagnosis of pulmonary TB (AFB smear-positive or culture-positive)
• HIV infected
• CD4 count greater than 350 cells/mm3
• Residence within 20 km of Kampala, Uganda
• Willing to use acceptable forms of contraception during the study and for 6 weeks after stopping study medication
• Parent or guardian willing to provide informed consent, if applicable

Exclusion Criteria

• Pregnancy

• Minimum Eligible Age: 13 Years
• Maximum Eligible Age: 60 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Makerere University

OTHER

Sponsor Role: collaborator

National Institute of Allergy and Infectious Diseases (NIAID)

NIH

Sponsor Role: lead

Responsible Party

Case Western Reserve University

Principal Investigators

Christopher C. Whalen, MD

Role: PRINCIPAL_INVESTIGATOR

Case Western Reserve University

Roy Mugerwa, MD

Role: PRINCIPAL_INVESTIGATOR

Makerere University

Diane Havlir, MD

Role: PRINCIPAL_INVESTIGATOR

University of California, San Francisco

Locations

Makerere University Medical School

Kampala, , Uganda

Countries

Uganda

References

Chamie G, Charlebois ED, Srikantiah P, Walusimbi-Nanteza M, Mugerwa RD, Mayanja H, Okwera A, Whalen CC, Havlir DV. Mycobacterium tuberculosis microbiologic and clinical treatment outcomes in a randomized trial of immediate versus CD4(+)-initiated antiretroviral therapy in HIV-infected adults with a high CD4(+) cell count. Clin Infect Dis. 2010 Aug 1;51(3):359-62. doi: 10.1086/654799.

Reference Type: DERIVED

PMID: 20569064 (View on PubMed)

Other Identifiers

1R01AI051219-01A2

Identifier Type: NIH

Identifier Source: secondary_id

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1R01AI051219-01A2

Identifier Type: NIH

Identifier Source: org_study_id

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