Immediate Versus Deferred Start of Anti-HIV Therapy in HIV-Infected Adults Being Treated for Tuberculosis

Tuberculosis (TB) is the most important co-infection 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 antiretroviral
therapy (ART) shortly after initiating TB treatment may improve outcomes in individuals
co-infected with HIV and TB. However, data to support this suggestion were limited before
this study began. This study will determine the most appropriate time to initiate ART in
HIV-infected individuals who recently initiated treatment for TB.

This study lasted 48 weeks and comprised two steps. At study entry, participants underwent
clinical assessment, drug adherence training, and blood collection. In Step 1, participants
were randomly assigned to one of two arms. Participants in Arm A initiated ART after
approximately 2 weeks of TB treatment. Participants in Arm B deferred ART until after 8 to 12
weeks of TB treatment. In Step 2, Arm B participants initiated ART; Arm A participants did
not enter Step 2. ART consisted of efavirenz (EFV) and emtricitabine (FTC)/tenofovir
disoproxil fumarate (TDF); FTC and TDF could be given as individual agents. Drug
substitutions could be made for participants who could not tolerate the specified regimen.
Blood collection and clinical assessments occurred at weeks 4, 8, 12, 16, 24, 32, 40, and 48.

Inclusion Criteria:

- HIV-infected.

- 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.

- Receipt of 1-14 cumulative days of rifampin- or other rifamycin-based TB treatment
that was initiated within 28 days prior to study entry.

- CD4 count less than 250 cells/mm^3 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.

- Karnofsky performance score =>20 at time of study entry.

Exclusion Criteria:

- ART for longer than 7 cumulative days prior to study entry or treatment for any period
of time with one or more antiretrovirals. Participants who have taken ART during
pregnancy or for occupational exposure 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.

- Breastfeeding.