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
  Purpose

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 Intervention Phase
HIV Infections
Tuberculosis
Drug: Abacavir
Drug: Lamivudine
Drug: Zidovudine
Drug: Tuberculosis treatment
Phase 3

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: Delaying HIV Disease Progression With Punctuated Antiretroviral Therapy in HIV-Associated Tuberculosis

Resource links provided by NLM:


Further study details as provided by National Institute of Allergy and Infectious Diseases (NIAID):

Primary Outcome Measures:
  • CD4+ decline (slope) [ Time Frame: Throughout study ] [ Designated as safety issue: No ]
  • Time to AIDS [ Time Frame: Throughout study ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • 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 ]

Estimated Enrollment: 350
Study Start Date: October 2004
Arms Assigned Interventions
Experimental: 1
Participants will receive 6 months of ARV therapy and treatment for TB
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: 2
Participants will not receive ARV therapy until CD4 counts drop below 250 cells/mm3. All participants will receive treatment for TB.
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

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.

  Eligibility

Ages Eligible for Study:   13 Years to 60 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00078247

Locations
Uganda
Makerere University Medical School
Kampala, Uganda
Sponsors and Collaborators
Makerere University
Investigators
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
  More Information

Additional Information:
No publications provided by National Institute of Allergy and Infectious Diseases (NIAID)

Additional publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
Responsible Party: Christopher C. Whalen, MD, Case Western Reserve University
ClinicalTrials.gov Identifier: NCT00078247     History of Changes
Other Study ID Numbers: 1R01AI051219-01A2, 1 R01 AI051219-01A2
Study First Received: February 20, 2004
Last Updated: August 10, 2010
Health Authority: United States: Federal Government

Keywords provided by National Institute of Allergy and Infectious Diseases (NIAID):
Antiretroviral Therapy
Africa

Additional relevant MeSH terms:
HIV Infections
Acquired Immunodeficiency Syndrome
Tuberculosis
Disease Progression
Lentivirus Infections
Retroviridae Infections
RNA Virus Infections
Virus Diseases
Sexually Transmitted Diseases, Viral
Sexually Transmitted Diseases
Immunologic Deficiency Syndromes
Immune System Diseases
Slow Virus Diseases
Mycobacterium Infections
Actinomycetales Infections
Gram-Positive Bacterial Infections
Bacterial Infections
Disease Attributes
Pathologic Processes
Zidovudine
Lamivudine
Abacavir
Anti-HIV Agents
Antimetabolites
Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions
Reverse Transcriptase Inhibitors
Nucleic Acid Synthesis Inhibitors
Enzyme Inhibitors
Anti-Retroviral Agents

ClinicalTrials.gov processed this record on July 31, 2014