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Tuberculosis is a leading cause of morbidity and mortality worldwide. Patients with extensively drug-resistant tuberculosis (XDR-TB) have had high mortality rates, especially when coinfected with HIV.A retrospective cohort study of the first 206 patients treated for XDR-TB in Eastern Cape Province, South Africa, October 2006 to January 2008, a province that has treated multidrug-resistant tuberculosis since 2000. All 206 patients were hospitalized for treatment until monthly sputum specimens were culture negative.Sixty-five patients diagnosed with XDR-TB died before XDR-TB treatment start. Among 195 patients starting treatment with a known HIV status, 108 (55.4%) were HIV positive, and 86 patients (44.1%) died during the first year of treatment. HIV-positive patients receiving antiretroviral treatment (ARVs) fared and HIV-negative patients, and more of both these groups survived than HIV-positive patients not on ARVs. However, HIV-negative patients experienced more serious adverse events requiring the withdrawal of medications than did HIV-positive patients, regardless of the use of ARVs.Experience in Eastern Cape Province, South Africa, suggests that patients can be treated for both XDR-TB and HIV. We have also shown that such combination therapy can be well tolerated by patients.