Impact of Antiretroviral Therapy on Tuberculosis Incidence Among HIV-Positive Patients in High-Income Countries

Background. The lower tuberculosis incidence reported in human immunodeficiency virus (HIV)-positive individuals receiving combined antiretroviral therapy (cART) is difficult to interpret causally. Furthermore, the role of unmasking immune reconstitution inflammatory syndrome ( IRIS) is unclear. We aim to estimate the effect of cART on tuberculosis incidence in HIV-positive individuals in high-income countries. Methods. The HIV-CAUSAL Collaboration consisted of 12 cohorts from the United States and Europe of HIV-positive, ART-naive, AIDS-free individuals aged >= 18 years with baseline CD4 cell count and HIV RNA levels followed up from 1996 through 2007. We estimated hazard ratios (HRs) for cART versus no cART, adjusted for time-varying CD4 cell count and HIV RNA level via inverse probability weighting. Results. Of 65 121 individuals, 712 developed tuberculosis over 28 months of median follow-up (incidence, 3.0 cases per 1000 person-years). The HR for tuberculosis for cART versus no cART was 0.56 (95% confidence interval [CI], 0.44-0.72) overall, 1.04 (95% CI, 0.64-1.68) for individuals aged > 50 years, and 1.46 (95% CI, 0.70-3.04) for people with a CD4 cell count of < 50 cells/mu L. Compared with people who had not started cART, HRs differed by time since cART initiation: 1.36 (95% CI, 0.98-1.89) for initiation < 3 months ago and 0.44 (95% CI, 0.34-0.58) for initiation >= 3 months ago. Compared with people who had not initiated cART, HRs < 3 months after cART initiation were 0.67 (95% CI, 0.38-1.18), 1.51 (95% CI, 0.98-2.31), and 3.20 (95% CI, 1.34-7.60) for people < 35, 35-50, and > 50 years old, respectively, and 2.30 (95% CI, 1.03-5.14) for people with a CD4 cell count of < 50 cells/mu L. Conclusions. Tuberculosis incidence decreased after cART initiation but not among people > 50 years old or with CD4 cell counts of < 50 cells/mu L. Despite an overall decrease in tuberculosis incidence, the increased rate during 3 months of ART suggests unmasking IRIS.