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HIV Coinfection in Multidrug- and Extensively Drug-Resistant Tuberculosis Results in High Early Mortality

¹ Departments of Medicine and Epidemiology & Population Health, Albert Einstein College of Medicine and Montefiore Medical Center, Bronx, New York; ² Department of Medicine, University of California, San Francisco, San Francisco, California; ³ Italian Cooperation, KwaZulu-Natal Department of Health, Pietermaritzburg, South Africa; ⁴ Philanjalo & Church of Scotland Hospital, Tugela Ferry, South Africa; ⁵ Harvard Medical School, Boston, Massachusetts; ⁶ Istituto Superiore di Sanita, KwaZulu-Natal Department of Health, Rome, Italy; ⁷ Enhancing Care Initiative KZN, University of KwaZulu-Natal, Durban, South Africa; and ⁸ Department of Medicine, Yale University School of Medicine, New Haven, Connecticut

Correspondence and requests for reprints should be addressed to Neel R. Gandhi, M.D., 111 E. 210th Street, Division of General Internal Medicine, Montefiore Medical Center, Bronx, NY 10467. E-mail: neelgandhi{at}alumni.williams.edu

Rationale: The multidrug-resistant (MDR) and extensively drug-resistant (XDR) tuberculosis (TB) epidemics are rapidly expanding in South Africa. Our initial report of HIV-associated XDR TB in South Africa revealed rapid and near complete mortality. Lower mortality has been described in the literature, but few of these patients have been HIV coinfected.

Objectives: To characterize mortality from MDR and XDR TB in a setting with high HIV-coinfection rates.

Methods: We conducted a retrospective observational study among 654 MDR and XDR TB cases diagnosed in Tugela Ferry, South Africa, from 2005 to 2007. Demographics and HIV status were abstracted from available medical records.

Measurements and Main Results: Survival was determined from the date of sputum collection until October 2008 and correlated with year of diagnosis and drug-susceptibility test results. From 2005 to 2007, 272 MDR TB and 382 XDR TB cases were diagnosed; HIV-coinfection rates were 90 and 98%, respectively. One-year mortality was 71% for MDR and 83% for XDR TB patients; 40% of MDR TB and 51% of XDR TB cases died within 30 days of sputum collection. One-year mortality among both MDR and XDR TB patients improved from 2005 to 2007; however, the majority of deaths still occurred within the first 30 days. One-year and 30-day mortality rates were worse with greater degree of drug resistance (P < 0.001).

Conclusions: Mortality from MDR and XDR TB in this high HIV-prevalence region is extraordinarily high, particularly within the first 30 days. Efforts to reduce mortality must focus on earlier diagnosis and early initiation of second-line TB and antiretroviral therapy.

Key Words: Mycobacterium tuberculosis • AIDS • multiple antibacterial drug-resistance • survival • South Africa

AT A GLANCE COMMENTARY Scientific Knowledge on the Subject Patients with MDR and XDR TB have achieved treatment success rates of 60 to 80% and 44 to 60%, respectively, in low HIV–prevalence settings. What This Study Adds to the Field Patients with MDR and XDR TB and HIV coinfection have markedly higher mortality rates than those previously reported in low HIV–prevalence settings.