Screening for tuberculosis with Xpert MTB/RIF versus fluorescent microscopy among adults newly diagnosed with HIV in rural Malawi: a cluster randomized trial (CHEPETSA).

Background: Tuberculosis (TB) remains the leading cause of death among HIV-positive individuals globally. Screening for TB at the point of HIV diagnosis with a high-sensitivity assay presents an opportunity to reduce mortality.

Methods: We performed a cluster randomized trial of TB screening among adults newly diagnosed with HIV in 12 primary health clinics in rural Thyolo, Malawi (clinicaltrials.gov NCT01450085). Clinics were allocated in a 1:1 ratio to perform either point-of-care Xpert MTB/RIF (Xpert) or point-of-care light-emitting diode fluorescence microscopy (LED FM) for individuals screening positive for TB symptoms. Asymptomatic participants were offered isoniazid preventive therapy in both arms. Investigators, but not clinic staff or participants, were masked to allocation. Our primary outcome was the incidence rate ratio (RR) of all-cause mortality within 12 months of HIV diagnosis.

Results: Prevalent TB was diagnosed in 24 (2.4%) of 1001 individuals enrolled in clinics randomized to Xpert, versus 10 (1.2%) of 841 in clinics randomized to LED FM. All-cause mortality was 22% lower in the Xpert arm than in the LED FM arm (6.7 versus 8.6 per 100 person-years, RR 0.78; 95% confidence interval [CI]: 0.58-1.06). A planned subgroup analysis suggested that participants with more advanced HIV (World Health Organization clinical stage III or IV) disease had lower mortality in clinics randomized to Xpert than to LED FM (RR 0.43, 95%CI: 0.22-0.87).

Conclusion: In rural Malawi, using point-of-care Xpert MTB/RIF to test symptomatic patients for TB at the time of HIV diagnosis reduced all-cause 12-month mortality among individuals with advanced HIV.