Timing of antiretroviral treatment, immunovirologic status, and TB risk: Implications for testing and treatment

Background: Tuberculosis (TB) risk and mortality increase in the 6 months after highly active antiretroviral therapy (HAART) initiation. This short-term risk may be a consequence of HAART initiation and immune reconstitution. Alternatively, it may be due to confounding by low CD4⁺ counts and high HIV viral loads (VLs). We assessed the TB risk before and after HAART initiation while appropriately controlling for time-updated laboratory values and HAART exposure. Methods: We conducted an observational cohort study among persons enrolled in the North American AIDS Cohort Collaboration on Research and Design from 1998 through 2011. A marginal structural model was constructed to estimate the association of HAART initiation and TB risk. Inverse probability weights for the probability of HAART initiation were incorporated. Results: Among 26,342 patients, 94 cases of TB were diagnosed during 147,557 person-years (p-y) of follow-up. The unadjusted TB rates were 93/100,000 p-y [95% confidence interval (CI): 63 to 132] before HAART initiation, 203/100,000 p-y (95% CI: 126 to 311) ≤6 months after HAART initiation, and 40/100,000 p-y (95% CI: 29 to 55) >6 months on HAART. After controlling for time-updated laboratory values, the adjusted odds of TB ≤6 months after HAART initiation and >6 months was 0.65 (95% CI: 0.28 to 1.51) and 0.29 (95% CI: 0.16 to 0.53), respectively. Conclusions: TB risk in the first 6 months after HAART initiation is not higher than that before HAART initiation after adjusting for CD4⁺ count and VLs. These findings suggest that short-term TB risk may be related to low CD4⁺ counts and high VLs near HAART initiation and support early HAART initiation to decrease TB risk.