Breakthrough Tuberculosis in a Large Cohort of People Living With HIV on Preventive Treatment.

Background Tuberculosis is a leading infectious cause of death globally and the main cause among those with HIV. TB preventive treatment (TPT) is key for preventing TB in people with HIV (PWH). Healthcare workers often worry about adverse effects of TPT regimens, including breakthrough TB-active TB during treatment. The burden of breakthrough TB remains largely unknown. This study aimed to determine the incidence and factors associated with breakthrough TB in PWH receiving HIV care. Methods We analysed the nationwide electronic patient management system (EPMS) for HIV care and TB registers in Namibia, following PWH registered for HIV care to determine TB incidence before, during and after TPT and applying logistic regression to determine factors associated with breakthrough TB. Results Of 334,606 PWH reviewed, 46,199 developed TB before, during, or after receiving TPT while being followed up for HIV care. PWH were followed for 114,667 patient-years (PYs) while receiving TPT, with breakthrough TB incidence of 1.40 per 100 PYs (95% CI: 1.33-1.47). The 1790 true breakthrough cases had a median age of 37 (IQR 30-45). Median time to breakthrough TB was 2.5 months. Only 43 (2.4%) cases were drug-resistant TB. In a logistic regression model comparing breakthrough versus non-breakthrough TB cases, receiving ART increased breakthrough TB risk (aOR = 2.88; 95% CI: 1.07-7.78). The 3 month isoniazid-rifapentine TPT regimen showed lower risk (aOR = 0.46; 95% CI: 0.36-0.63) than the 6 month isoniazid regimen, while 9H increased risk (aOR = 1.44; 95% CI: 1.18-2.52) but incidence rates were comparable between the regimens. Conclusion The incidence of breakthrough TB was low at 1.4 per 100 PYs of TPT provision but indicating a need for improved screening of PWH before TPT. The incidence rate of TB among PWH during and after the shorter TPT regimen (3HP) is comparable to that of the 6H and 9H regimens.