Estimates suggest the global tuberculosis [TB] epidemic will result in 90 million new cases this decade, with the highest incidence rates occurring in sub-Saharan Africa where the prevalence of HIV infection is also high. This growing interface between the HIV and TB epidemics has raised concerns regarding the efficacy of conventional antituberculosis therapy in HIV/TB patients. Higher rates of TB-associated mortality, acquired drug-resistance, and relapse have been reported in TB patients with HIV. A potential explanation for these adverse outcomes is the low bioavailability of oral medications in HIV patients. Preliminary evidence suggests the oral absorption of anti-tuberculosis drugs is unreliable in HIV-infected patients, and that more than 30 % of all HIV-infected patients may malabsorb their drugs. This proposal outlines a 3 year prospective cohort study of 540 TB patients admitted to the Princess Marina Hospital in Gaborone, Botswana. Baseline, clinical, microbiologic, and laboratory data, including HIV serologies and serum for isoniazid (H), rifampin (R), ethambutol (E), and pyrazinamide (P) concentrations will be obtained. Patients will be followed for 18 months after the completion of therapy to assess outcome. A cross-sectional survey of the first 100 patients enrolled will be performed to measure the prevalence of drug malabsorption, and to identify risk factors and possible mechanisms for malabsorption. Patients who die of TB while on therapy, acquire drug-resistance, or relapse following therapy will be identified and incidence rates will be determined. Patients who die of TB or relapse will serve as case patients in different nested case-control studies to determine the therapeutic significance of malabsorption.
