Factors Associated With And Characteristic of HIV/Tuberculosis Co-Infection: A Retrospective Analysis of SECOND-LINE Clinical Trial Participants.

BACKGROUND Tuberculosis (TB) is a common infection in people living with HIV. However, the risk factors for HIV/TB co-infection in second-line HIV therapy are poorly understood. We aimed to determine the incidence and risk factors for TB co-infection in SECOND-LINE, an international randomised clinical trial of second-line HIV therapy. METHODS We did a cohort analysis of TB cases in SECOND-LINE. TB cases included any clinical or laboratory-confirmed diagnoses and/or commencement of treatment for TB following randomisation. Baseline factors associated with TB were analysed using Cox regression stratified by site. RESULTS TB cases occurred at sites in Argentina, India, Malaysia, Nigeria, South Africa and Thailand, in a cohort of 355 of the 541 SECOND-LINE participants. Overall, 20 cases of TB occurred, an incidence rate of 3.4 per 100 person-years (95% CI 2.1-5.1). Increased TB risk was associated with a low CD4+ cell count (≤200 cells/μL), high viral load (>200 copies/mL), low platelet count (<150 x109/L) and low total serum cholesterol (≤4.5mmol/L) at baseline. An increased risk of death was associated with TB, adjusted for CD4, platelets, and cholesterol. A low CD4+ cell count was significantly associated with incident TB, mortality, other AIDS diagnoses, and virologic failure. DISCUSSION The risk of TB remains elevated in PLHIV in the setting of second-line HIV therapy in TB endemic regions. TB was associated with a greater risk of death. Finding that low CD4+ T cell count was significantly associated with poor outcomes in this population supports the value of CD4+ monitoring in HIV clinical management.