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Effect of Antiretroviral Therapy on Treatment Outcomes in a Prospective Study of Extensively Drug-Resistant Tuberculosis (XDR-TB) HIV Coinfection Treatment in KwaZulu-Natal, South Africa

Yuengling, Katharine A., MPH*; Padayatchi, Nesri, MD; Wolf, Allison, MPH; Mathema, Barun, PhD, MPH*; Brown, Tyler, MD§; Horsburgh, C. Robert, MD║,¶; O'Donnell, Max R., MD, MPH*,†,‡

JAIDS Journal of Acquired Immune Deficiency Syndromes: December 1, 2018 - Volume 79 - Issue 4 - p 474–480
doi: 10.1097/QAI.0000000000001833
Clinical Science

Background: Extensively drug-resistant tuberculosis (XDR-TB)/HIV coinfection has been associated with high mortality and poor TB outcomes. We performed a prospective study to comprehensively characterize a cohort of patients with XDR-TB.

Methods: Adult patients with XDR-TB were enrolled at treatment initiation at a TB referral hospital in KwaZulu-Natal Province, South Africa, and followed through the end of treatment. Clinical data, questionnaires, adherence data, and sputum were collected monthly. Whole genome sequencing was performed on baseline Mycobacterium tuberculosis (MTB) isolates. Treatment outcomes were defined using standard definitions.

Results: One hundred five patients with XDR-TB (76.1% HIV-infected) were enrolled from August 2009 to July 2011. Among HIV-coinfected patients, 82.5% were on antiretroviral therapy initially and 93.8% cumulatively over the study period. At 24 months, 31.4% had a successful outcome and 68.6% had an unsuccessful outcome with 41% mortality. Antiretroviral therapy was associated with improved mortality in HIV-coinfected patients (P = 0.05), as was TB culture conversion (P < 0.0001). On whole genome sequencing, most strains were LAM4/KZN lineage (68%), with few single nucleotide polymorphism differences.

Conclusions: Despite improved HIV care, treatment outcomes and mortality were only modestly improved compared with previous South African XDR-TB/HIV treatment cohorts. Of note, this study was completed before the introduction of new antimycobacterial agents (eg, bedaquiline and delamanid). As new TB drugs and regimens become available, it is important to monitor treatment to ensure that benefits seen in clinical trials are reproduced in high-burden, low-resource settings.

*Department of Epidemiology, Mailman School of Public Health, Columbia University, New York, NY;

Centre for AIDS Programme of Research in South Africa (CAPRISA), Durban, South Africa;

Division of Pulmonary, Allergy, and Critical Care Medicine, Columbia University Medical Center, New York, NY;

§Infectious Disease Division, Massachusetts General Hospital, Boston, MA;

Department of Medicine, Boston University School of Medicine, Boston, MA; and

Department of Epidemiology, Boston University School of Public Health, Boston, MA.

Correspondence to: Max O'Donnell, Suite E101, 8th floor, PH building, 622 W. 168th street, New York, NY 10032 (e-mail:

Supported by the National Institutes of Health/National Institute of Allergy and Infectious Disease K23 [AI098479-01A1]; Gerstner Family Foundation, Doris Duke Clinical Scientist Career Development Award to M.O.; and CAPRISA MRC TB-HIV Pathogenesis Unit.

Presented at: (1) TB 2016: Science and Solidarity preconference to the AIDS 2016 Conference; July 16, 2016; Durban, South Africa. (2) American Thoracic Society 2016 International Conference; May 17, 2016; San Francisco, CA.

The authors have no conflicts of interest to disclose.

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Received March 07, 2018

Accepted June 25, 2018

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