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

• Percent of Participants Who Survived Without AIDS Progression. [ Time Frame: Through week 48 ] [ Designated as safety issue: Yes ]
  As this was a study of the strategy of providing antiretroviral therapy (ART) during the initial treatment of TB versus deferring ART until TB was treated for 8-12 weeks, all eligible participants randomized were followed for 48 weeks, whether they started ART as scheduled, whether they started ART at all, or even if the participant did not have TB and discontinued TB treatment. The percent surviving without a new AIDS-defining illness was calculated using a Kaplan-Meier estimator with an associated standard error.
  
  

• Percent of Participants Reporting a Grade 3 or 4 Adverse Event or Laboratory Abnormality [ Time Frame: Through week 48 ] [ Designated as safety issue: Yes ]
  All eligible participants were included in this analysis. The percent of participants whose highest reported grade of adverse events and laboratory abnormalities was Grade 3 or 4 was calculated with an associated standard error, where Grade 1=mild, Grade 2=moderate, Grade 3=severe, Grade 4=life threatening/disabling, and Grade 5=death.
  
  
• Time to First New AIDS-defining Illness or Death. [ Time Frame: Through week 48 ] [ Designated as safety issue: No ]
  All eligible participants were included in this analysis. Weeks from randomization to first new AIDS-defining illness or death was analyzed using a stratified Cox proportional hazards regression model. The stratification was by screening CD4 cell count: <50 cells/mm3 versus =>50 cells/mm3.
  
  
• Percent of Participants With Culture-confirmed Tuberculosis (TB) Who Survived Without AIDS Progression. [ Time Frame: Through week 48 ] [ Designated as safety issue: Yes ]
  This analysis was based on 374 participants with culture-confirmed TB at entry. The percent with culture-confirmed TB surviving without a new AIDS-defining illness was calculated using a Kaplan-Meier estimator with an associated standard error.
  
  
• Percent of Participants Who Interrupted or Discontinued at Least One Tuberculosis (TB) Medication Due to Toxicity. [ Time Frame: Through week 48 ] [ Designated as safety issue: Yes ]
  All eligible participants were included in this analysis. The percent of participants who interrupted at least one TB medication for more than one day due to toxicity or discontinued at least one TB medication due to toxicity was calculated with an associated standard error.
  
  
• Percent of Participants With Confirmed or Probable Tuberculosis (TB) Whose TB Resolved, or Who Required TB Treatment Through the End of Follow-up, or Died, or Were Lost to Follow-up. [ Time Frame: Through week 48 ] [ Designated as safety issue: Yes ]
  TB treatment outcome was assessed in the 800 eligible participants who had confirmed or probable TB at study entry. The sites determined if the TB was resolved. If TB was not resolved, TB treatment outcome status was determined based on whether TB treatment was ongoing at the last study visit; if the participant died while TB treatment was ongoing; or if the participant was lost to follow-up, withdrew consent, or other reason for lacking TB resolution status. Percents were calculated with associated standard errors.
  
  
• Percent of Participants Whose CD4 Increased by at Least 100 Cells/mm^3 Between Baseline and Week 48. [ Time Frame: Through week 48 ] [ Designated as safety issue: No ]
  All eligible participants were included in the analysis. Participants who were lost-to-follow-up (LFU) prior to week 48 or who were alive with a CD4 cell count increase of less than 100 cells/mm^3 were grouped separately those who died or whose CD4 cell count increased by at least 100 cells/mm^3. Participants missing CD4 cell counts at week 48 were coded as LFU in this analysis. The percents were calculated with associated standard errors.
  
  
• Percent of Participants With MTB IRIS. [ Time Frame: Through week 48 ] [ Designated as safety issue: Yes ]
  All eligible participants were included in this analysis. The percent of participants with Mycobacteria tuberculosis (MTB)-associated immune reconstitution inflammatory syndrome (IRIS) was calculated with an associated standard error.
  
  
• Percent of Participants With HIV IRIS. [ Time Frame: Through week 48 ] [ Designated as safety issue: Yes ]
  All eligible participants were included in this analysis. The percent of participants with HIV-associated immune reconstitution inflammatory syndrome (IRIS) was calculated with an associated standard error.
  
  
• Percent of Participants Whose HIV Viral Load Was Less Than 400 Copies/mL at Week 48. [ Time Frame: Through week 48 ] [ Designated as safety issue: No ]
  All eligible participants were included in the analysis. Participants who were lost-to-follow-up (LFU) prior to week 48 or who were alive with a HIV viral load at least 400 copies/mL were grouped separately those those who died or who had HIV viral loads below 400 copies/mL. Participants missing HIV viral loads at week 48 were coded as LFU in this analysis. Percents were calculated with associated standard errors.
  
  

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.