The purpose of this study is to determine the best time to begin anti-HIV treatment in individuals who have HIV and tuberculosis (TB).

Study hypothesis: Immediate antiretroviral therapy (ART), initiated within approximately 2 weeks after initiation of TB treatment, will reduce the frequency of other AIDS-defining illnesses and death in HIV infected participants being treated for TB by at least 40% by Week 48 when compared to deferred ART initiated at least 8 weeks after initiation of TB treatment.

TB is the most important coinfection in the HIV epidemic; the bi-directional relationship between the two diseases is well established. HIV increases the risk for TB acquisition, reactivation, and reinfection, and reduces survival compared to patients with TB alone. In individuals with HIV, TB infection results in reduced survival, increased risk for opportunistic infections, and elevations in HIV replication. Improving the outcome of HIV infected individuals who develop TB is of high importance. Initiating ART shortly after initiating TB treatment may improve outcomes in individuals coinfected with HIV and TB. However, data to support this suggestion are limited. This study will determine the most appropriate time to initiate ART in HIV infected individuals who recently initiated treatment for TB.

This study will last 48 weeks and will comprise two steps. At study entry, participants will undergo clinical assessment, drug adherence training, and blood collection. In Step 1, participants will be randomly assigned to one of two arms. Participants in Arm A will initiate ART within 2 weeks after initiating TB treatment. Participants in Arm B will defer ART until 8 to 12 weeks after initiation of their TB treatment. In Step 2, Arm B participants will initiate ART; Arm A participants will not enter Step 2. ART will consist of efavirenz and emtricitabine (FTC)/tenofovir disoproxil fumarate (TDF); FTC and TDF may be given as individual agents. Drug substitutions may be made for participants who cannot tolerate the specified regimen. Blood collection and clinical assessments will occur at Weeks 4, 8, 12, 16, 24, 32, 40, and 48.

Ages Eligible for Study:  13 Years and above,  Genders Eligible for Study:  Both

Criteria

Inclusion Criteria:

• HIV infection
• Confirmed or probable TB. More information on the criterion can be found in the protocol.
• Chest x-ray within 30 days prior to study entry
• Current rifampin- or other rifamycin-based TB treatment initiated within 14 days prior to study entry
• CD4 count less than 200 cells/mm3 within 30 days prior to study entry
• Willing to use acceptable methods of contraception while on study drugs and for 6 weeks after stopping these drugs
• Able to swallow oral medications
• Parent of guardian willing to provide informed consent, if applicable

Exclusion Criteria:

• ART for longer than 7 days prior to study entry or treatment for any period of time with two or more antiretrovirals in combination. Participants who have taken nevirapine or zidovudine during pregnancy are not excluded.
• Allergy or sensitivity to any of the study drugs or their formulations
• History of multidrug-resistant TB
• Receipt of any investigational therapy or chemotherapy within 30 days prior to study entry
• Certain medications
• Pregnancy or breastfeeding