Risk of severe bacterial infections including TB before and after immediate or deferred antiretroviral therapy: A multicenter, prospective, cohort study

Objectives: Deferring antiretroviral therapy (ART) until a CD4 count below cells/mm³ or other clinical indication in people with HIV (PWH) carries an increased risk of severe bacterial infections and tuberculosis (TB). It is not known if this increased risk is reversed after ART initiation. Methods: We analyzed 4684 adult PWH with CD4 cell counts above 500 cells/mm³ who were randomized to immediate or deferred ART in the Strategic Timing of AntiRetrovial Treatment trial. In May 2015, the deferred group was offered ART and follow-up continued until December 2021. Cox proportional hazards models were used to compare the risks of severe bacterial infections including TB in the immediate and deferred groups before and after ART initiation in the deferred group. Results: A total of 217 (4.6%) participants experienced a severe bacterial infection during the entire follow-up period. Pre-2016, the immediate group had a lower rate of severe bacterial infections compared to the deferred group (hazard ratio [HR] 0.38; 95% CI 0.26, 0.55). During 2016-2021, there was no longer a statistically significant difference (HR 0.75; 95% CI 0.49, 1.16). No differences were observed between clinical or demographic subgroups. Conclusion: The increased risk of severe bacterial infections seen after deferring ART is reversed once ART is initiated.