Anti-HIV Drugs for Ugandan Patients With HIV and Tuberculosis

HIV Infections Clinical Trial

Official title:

Delaying HIV Disease Progression With Punctuated Antiretroviral Therapy in HIV-Associated Tuberculosis

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00078247
• Other study ID #: 1R01AI051219-01A2
• Secondary ID: 1R01AI051219-01A
• Status: Completed
• Phase: Phase 3
• First received: February 20, 2004
• Last updated: August 10, 2010
• Start date: October 2004

Study information

• Verified date: August 2010
• Source: National Institute of Allergy and Infectious Diseases (NIAID)
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Federal Government
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 350
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 13 Years to 60 Years

Eligibility

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

Study Design

Allocation: Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Parallel Assignment, Masking: Open Label, Primary Purpose: Treatment

Related Conditions & MeSH terms

• HIV Infections
• Tuberculosis

Intervention

Drug:
• Abacavir
300 mg tablet taken orally twice daily
• Lamivudine
300 mg tablet taken orally daily
• Zidovudine
300 mg tablet taken orally twice daily
• Tuberculosis treatment
Tuberculosis treatment

Locations

Country	Name	City	State
Uganda	Makerere University Medical School	Kampala

Sponsors (2)

Lead Sponsor	Collaborator
National Institute of Allergy and Infectious Diseases (NIAID)	Makerere University

Country where clinical trial is conducted

Uganda, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	CD4+ decline (slope)		Throughout study	No
Primary	Time to AIDS		Throughout study	No
Secondary	Safety		Throughout study	Yes
Secondary	Response to antituberculous therapy		Throughout study	No
Secondary	Immune reconstitution		Throughout study	No
Secondary	Viral drug resistance		Throughout study	No

External Links

•   Click here for more information about abacavir
•   Click here for more information on lamivudine
•   Click here for more information on zidovudine
•   Click here for the Uganda-Case Research Portfolio on Tuberculosis Web site