Anti-HIV Drugs for Ugandan Patients With HIV and Tuberculosis

Study Overview
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Brief Summary
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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
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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.

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

Conditions
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HIV Infections, Tuberculosis

Intervention / Treatment
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* Drug: Abacavir
* Drug: Lamivudine
* Drug: Zidovudine
* Drug: Tuberculosis treatment


Participation Criteria
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Eligibility Criteria
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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

Ages Eligible for Study
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Minimum Age: 13 Years
Maximum Age: 60 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: 1<br>Participants will receive 6 months of ARV therapy and treatment for TB | Drug: Abacavir<br>* 300 mg tablet taken orally twice daily<br>Drug: Lamivudine<br>* 300 mg tablet taken orally daily<br>Drug: Zidovudine<br>* 300 mg tablet taken orally twice daily<br>Drug: Tuberculosis treatment<br>* Tuberculosis treatment<br>|
| Experimental: 2<br>Participants will not receive ARV therapy until CD4 counts drop below 250 cells/mm3. All participants will receive treatment for TB. | Drug: Abacavir<br>* 300 mg tablet taken orally twice daily<br>Drug: Lamivudine<br>* 300 mg tablet taken orally daily<br>Drug: Zidovudine<br>* 300 mg tablet taken orally twice daily<br>Drug: Tuberculosis treatment<br>* Tuberculosis treatment<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| CD4+ decline (slope) |  | Throughout study | 
| Time to AIDS |  | Throughout study | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Safety |  | Throughout study | 
| Response to antituberculous therapy |  | Throughout study | 
| Immune reconstitution |  | Throughout study | 
| Viral drug resistance |  | Throughout study | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Antiretroviral Therapy, Africa