Anti-HIV Drugs for Ugandan Patients With HIV and Tuberculosis

This study has been completed.
Sponsor:
Collaborator:
Makerere University
Information provided by:
National Institute of Allergy and Infectious Diseases (NIAID)
ClinicalTrials.gov Identifier:
NCT00078247
First received: February 20, 2004
Last updated: August 10, 2010
Last verified: August 2010

February 20, 2004
August 10, 2010
October 2004
Not Provided
  • CD4+ decline (slope) [ Time Frame: Throughout study ] [ Designated as safety issue: No ]
  • Time to AIDS [ Time Frame: Throughout study ] [ Designated as safety issue: No ]
Not Provided
Complete list of historical versions of study NCT00078247 on ClinicalTrials.gov Archive Site
  • Safety [ Time Frame: Throughout study ] [ Designated as safety issue: Yes ]
  • Response to antituberculous therapy [ Time Frame: Throughout study ] [ Designated as safety issue: No ]
  • Immune reconstitution [ Time Frame: Throughout study ] [ Designated as safety issue: No ]
  • Viral drug resistance [ Time Frame: Throughout study ] [ Designated as safety issue: No ]
Not Provided
Not Provided
Not Provided
 
Anti-HIV Drugs for Ugandan Patients With HIV and Tuberculosis
Delaying HIV Disease Progression With Punctuated Antiretroviral Therapy in HIV-Associated Tuberculosis

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.

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.

Interventional
Phase 3
Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
  • HIV Infections
  • Tuberculosis
  • Drug: Abacavir
    300 mg tablet taken orally twice daily
  • Drug: Lamivudine
    300 mg tablet taken orally daily
  • Drug: Zidovudine
    300 mg tablet taken orally twice daily
  • Drug: Tuberculosis treatment
    Tuberculosis treatment
  • Experimental: 1
    Participants will receive 6 months of ARV therapy and treatment for TB
    Interventions:
    • Drug: Abacavir
    • Drug: Lamivudine
    • Drug: Zidovudine
    • Drug: Tuberculosis treatment
  • Experimental: 2
    Participants will not receive ARV therapy until CD4 counts drop below 250 cells/mm3. All participants will receive treatment for TB.
    Interventions:
    • Drug: Abacavir
    • Drug: Lamivudine
    • Drug: Zidovudine
    • Drug: Tuberculosis treatment
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.

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Completed
350
Not Provided
Not Provided

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
Both
13 Years to 60 Years
No
Contact information is only displayed when the study is recruiting subjects
Uganda
 
NCT00078247
1R01AI051219-01A2, 1 R01 AI051219-01A2
Not Provided
Christopher C. Whalen, MD, Case Western Reserve University
National Institute of Allergy and Infectious Diseases (NIAID)
Makerere University
Principal Investigator: Christopher C. Whalen, MD Case Western Reserve University
Principal Investigator: Roy Mugerwa, MD Makerere University
Principal Investigator: Diane Havlir, MD University of California, San Francisco
National Institute of Allergy and Infectious Diseases (NIAID)
August 2010

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP