More sensitive tests are needed for the diagnosis of smear-negative and HIV-associated tuberculosis. This study compares the sensitivities and specificities of three molecular tests, namely, the Xpert MTB/RIF test, the Xpert Ultra (Ultra), and RealTime MTB (RT-MTB), in a high HIV prevalence setting. Symptomatic adults were recruited from three outpatient sites, and each provided 4 sputum specimens. The diagnostic performance of Xpert MTB/RIF, Ultra, and RT-MTB was evaluated, with culture as a reference standard. HIV infection occurred in 62% of patients, with a median CD4 count of 220 cells/l. The Ultra test had the highest sensitivity of 89.3% (95% confidence interval [CI], 78.1 to 96) compared to those of the Xpert MTB/RIF at 82.1% (95% CI, 69.6 to 91.1; P ϭ 0.12) and RT-MTB at 78.6% (95% CI, 65.6 to 88.4; P ϭ 0.68). The specificity was highest with the Xpert MTB/RIF at 100% (95% CI, 98 to 100), followed by RealTime MTB at 96.7% (95% CI, 92.9 to 98.8; P ϭ 0.03) and the Ultra at 95.6% (95% CI, 91.5 to 98.1; P ϭ 0.08). In patients with smear-negative disease, the Ultra was more sensitive than the Xpert MTB/RIF (64.7% [95% CI, 38.3 to 85.8] versus 41.2% [95% CI, 18.4 to 67.1], respectively; P ϭ 0.12), and RT-MTB performed equally to Xpert MTB/RIF. In a comparison of the Ultra and RT-MTB on the same sputum specimen pellets, the Ultra was more sensitive than RT-MTB in the overall cohort (88.9% [95% CI, 77.4 to 95.8] versus 77.8% [95% CI, 64.4 to 88], respectively; P ϭ 0.03) and among people with HIV (87.5% [95% CI, 71 to 96.5] versus 68.6% [95% CI, 50 to 83.9], respectively; P ϭ 0.03). Although these results did not reach statistical significance, they suggest that the Ultra is more sensitive than the Xpert MTB/RIF and RT-MTB, most prominently in smear-negative disease. This was accompanied by a loss of specificity.

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Most (64%) second-line treatment failure in this clinic is related to adherence and can be overcome with careful adherence support. Controlled interventions are needed to determine what the optimal approach is to improving second-line outcomes and reducing the need for third-line ART.

No randomized clinical trials were found for WHO-recommended treatment of drug-resistant TB treatment where at least 20% of the cohort was coinfected with HIV. Nearly all patients (83%) experience ADR during DR-TB treatment. While no significant association between ADR and HIV coinfection was found, further research is needed to determine whether concomitant antiretrovirals or immunosuppression increases the risks for HIV-infected patients.