Retreatment TB is a risk factor for multidrug-resistant TB among people with HIV in rural eastern Uganda: A nested case-control study

• Risk factors for MDR-TB among people with HIV (PWH) are understudied. • We found that retreatment TB is strongly associated with MDR-TB among PWH. • We recommend that PWH with prior TB treatment require MDR-TB surveillance. • Additionally, treatment adherence support may benefit PWH with retreatment TB. People with human immunodeficiency virus (PWH) have an increased risk of multidrug-resistant TB (MDR-TB) compared to those without HIV. To investigate the risk factors for MDR-TB among PWH in rural eastern Uganda. We conducted a nested case–control study at Soroti Regional Referral Hospital in rural eastern Uganda. TB records from January 2017 to May 2024 were retrospectively reviewed to identify all PWH. MDR-TB was defined as resistance to at least both Isoniazid and Rifampicin following GeneXpert Mycobacterium TB and Rifampicin assay and culture-based drug-susceptible testing. Cases were PWH with MDR-TB, while controls were a random sample of PWH without MDR-TB, in a 1:3 ratio. Multivariable binary logistic regression was used to identify factors independently associated with being a case rather than a control. Adjusted odds ratios (aORs) and 95% confidence intervals (CIs) were reported. We included 37 cases and 111 controls, and found retreatment TB was associated with being a case rather than a control (aOR 6.97; 95% CI 2.65–19.46). Male sex (aOR: 1.59; 95% CI: 0.67–3.93), clinically diagnosed pulmonary TB (aOR: 0.38; 95% CI: 0.10–1.23) or extrapulmonary TB (aOR: 0.37; 95% CI: 0.05–1.62), and recent anti-retroviral therapy initiation (aOR: 2.07; 95% CI: 0.83–5.28) were insignificantly associated with being a case. This study showed that retreatment TB is associated with a higher likelihood of MDR-TB among PWH in a referral hospital in rural eastern Uganda. These findings underscore the need for intensified drug resistance surveillance and adherence support among PWH with prior TB treatment.