Risk of Tuberculosis After Achieving Human Immunodeficiency Virus Virological Suppression on Antiretroviral Therapy: A Danish Nationwide Prospective Cohort Study

Background. In countries with low tuberculosis burden, the risk of tuberculosis in people living with human immunodeficiency virus (HIV; PWH) once HIV virological suppression is achieved is not fully understood. Methods. In a nationwide cohort, we included all adult PWH from the Danish HIV Cohort initiating antiretroviral therapy (ART) (1995-2017) without prior tuberculosis disease. We used Kaplan-Meier estimation and Poisson regression to calculate the tuberculosis incidence rate (IR) after 6 months of ART, along with associated risk factors and mortality rates. Results. Among 6849 PWH initiating ART (median follow-up, 7.4 years), 84 developed tuberculosis (IR, 1.4/1000 person-years [PY]), 54 of them > 6 months after ART initiation (IR, 0.97/1000 PY [95% confidence interval [CI]: 1.17-1.79); 1.95/1000 PY [1.34- 2.76] in non-Danish born, 0.36/1000 PY [.21-.62] in Danish born without injection drug use (IDU), and 2.95/1000 PY [1.53-5.66] in Danish born with IDU). Danish-born individuals with suppressed viremia and no IDU or known tuberculosis exposures had the lowest risk (IR, 0.05/1000 PY). In the adjusted analysis, being non-Danish born (adjusted IR ratio, 4.27 [95% CI: 2.36-7.72]), IDU (4.95 [2.55-9.62]), and previous AIDS-defining events (2.05 [1.06-3.94]) raised the tuberculosis risk, while suppressed HIV RNA levels (0.58 [.34-.99]) reduced it. The overall mortality rate for HIV/tuberculosis coinfected after ART was high, at 48.9/1000 PY (95% CI: 30.4-78.7). Conclusions. The tuberculosis risk remains elevated in PWH beyond 6 months after ART initiation, especially among migrants, those with IDU, those without suppressed HIV RNA, and those exposed to areas highly endemic for tuberculosis or with social risk determinants of health. Conversely, PWH without these risk factors have a tuberculosis risk similar to the general population and would not require targeted tuberculosis screening strategies.