Tuberculosis Case Finding With Combined Rapid Point-of-Care Assays (Xpert MTB/RIF and Determine TB LAM) in HIV-Positive Individuals Starting Antiretroviral Therapy in Mozambique.

BACKGROUND: Tuberculosis is a major health concern in several countries, and effective diagnostic algorithms for use in human immunodeficiency virus (HIV)-positive patients are urgently needed. METHODS: At prescription of antiretroviral therapy, all patients in 3 Mozambican health centers were screened for tuberculosis, with a combined approach: World Health Organization (WHO) 4-symptom screening (fever, cough, night sweats, and weight loss), a rapid test detecting mycobacterial lipoarabinomannan in urine (Determine TB LAM), and a molecular assay performed on a sputum sample (Xpert MTB/RIF; repeated if first result was negative). Patients with positive LAM or Xpert MTB/RIF results were referred for tuberculosis treatment. RESULTS: Among 972 patients with a complete diagnostic algorithm (58.5% female; median CD4 cell count, 278/µL; WHO HIV stage I, 66.8%), 98 (10.1%) tested positive with Xpert (90, 9.3%) or LAM (34, 3.5%) assays. Compared with a single-test Xpert strategy, dual Xpert tests improved case finding by 21.6%, LAM testing alone improved it by 13.5%, and dual Xpert tests plus LAM testing improved it by 32.4%. Rifampicin resistance in Xpert-positive patients was infrequent (2.5%). Among patients with positive results, 22 of 98 (22.4%) had no symptoms at WHO 4-symptom screening. Patients with tuberculosis diagnosed had significantly lower CD4 cell counts and hemoglobin levels, more advanced WHO stage, and higher HIV RNA levels. Fifteen (15.3%) did not start tuberculosis treatment, mostly owing to rapidly deteriorating clinical conditions or logistical constraints. The median interval between start of the diagnostic algorithm and start of tuberculosis treatment was 7 days. CONCLUSIONS: The prevalence of tuberculosis among Mozambican HIV-positive patients starting antiretroviral therapy was 10%, with limited rifampicin resistance. Use of combined point-of-care tests increased case finding, with a short time to treatment. Interventions are needed to remove logistical barriers and prevent presentation in very advanced HIV/tuberculosis disease.

Low mortality rates at two years in HIV-infected individuals undergoing systematic tuberculosis testing with rapid assays at initiation of antiretroviral treatment in Mozambique.

BACKGROUND: Few studies have evaluated the mortality rate in individuals with HIV initiating antiretroviral therapy (ART), undergoing screening with combined or repeated rapid tests for tuberculosis (TB). METHODS: All individuals with HIV starting ART, irrespective of the presence of TB-related symptoms, received two consecutive Xpert tests plus a rapid test for the detection of mycobacterial lipoarabinomannan in urine (LAM). Mortality was evaluated by Kaplan-Meier analysis using the log-rank test in univariate analyses and Cox regression models with time-dependent covariates in multivariate analyses. RESULTS: Among 972 individuals screened with combined tests, 98 (10.1%) tested positive for TB with Xpert, LAM, or both. At the end of the study, 780 (80.2%) had completed 2 years of follow-up, 39 (4.0%) had died, and 153 (15.7%) were lost to follow-up. In the multivariate analyses, the factors significantly associated with mortality were missed ART (hazard ratio (HR) 7.05, 95% confidence interval (CI) 2.33-21.35), symptomatic HIV disease (WHO-HIV stage >1) (HR 3.31, 95% CI 1.28-8.54), and low CD4 count (<200/mm3) (HR 2.72, 95% CI 1.21-6.13), with no significant effect of TB status. In the subgroup of the 98 TB-positive individuals, only missed ART (HR 4.12, 95% CI 1.03-16.46) and missed anti-TB treatment (HR 9.25, 95% CI 2.65-32.28) were significantly associated with mortality. CONCLUSIONS: A low mortality rate was observed among individuals with HIV undergoing systematic testing for TB at initiation of ART. After adjusting for confounders, mortality was significantly associated with missed ART, advanced disease, and missed anti-TB treatment. These findings reinforce the need to promote early diagnosis of HIV and the adoption of screening strategies for TB that prevent presentation with severe disease.