Impact of HIV and hospitalization on the incidence of subsequent rifampicin-resistant tuberculosis after initiation of first-line tuberculosis treatment: a retrospective cohort study in South Africa

Abstract

Background: People living with human immunodeficiency virus (PLHIV) may have a higher risk of acquired rifampicin-resistance during first-line tuberculosis (TB) treatment, potentially driving the multi-drug or rifampicin-resistant tuberculosis (MDR/RR-TB) epidemic. Nosocomial transmission may further elevate MDR/RR-TB risk. We assessed the impact of HIV and hospitalization on subsequent MDR/RR-TB diagnosis among individuals starting first-line TB treatment. Methods: The retrospective cohort included individuals with laboratory-confirmed rifampicin-susceptible TB (RS-TB), who started TB treatment (2013–2021). Subsequent TB diagnoses (MDR/RR-TB and RS-TB) over 2 years’ follow-up from TB treatment initiation were assessed. Routine health service data utilized. Findings: A total of 190,945 individuals were included; median age 34.0 (interquartile range (IQR), 25.5–44.9); 79,160 (42%) female and 69,636 (37%) PLHIV. Overall, 6870 (9.9%) PLHIV and 9342 (7.7%) HIV-negative individuals were diagnosed with recurrent TB within 24 months. Rifampicin drug susceptibility testing was available for 5354 (77.9%) and 8154 (87.3%) PLHIV and HIV-negative individuals, respectively. PLHIV with advanced HIV (cluster of differentiation 4 (CD4) <200 cells/μl) (adjusted-hazard ratio (HR) 2.86, 95% confidence interval (CI), 2.60–3.15) and individuals hospitalized (adjusted-HR 2.76, 95% CI, 2.50–3.05) for ≥1 week had significantly increased MDR/RR-TB risk compared to HIV-negative and non-hospitalized individuals, respectively. PLHIV had a higher risk of MDR/RR-TB relative to all other recurrent TB, regardless of CD4. Interpretation: This study suggests that PLHIV may have an increased risk of both acquiring rifampicin-resistance during TB treatment and re- or super-infection with already resistant Mycobacterium tuberculosis strain during hospitalization. While not causal, these data suggest the need for improved TB treatment for PLHIV including tailored drug regimens, potentially with increased rifampicin dosages, and emphasize the importance of TB infection control in healthcare settings.