The Impact of Concurrent Antiretroviral Therapy and MDR-TB Treatment on Adverse Events

• Type of Material: Article
• Authors: Jonathan P. Smith, Emory University; Neel Gandhi, Emory University; Sarita Shah, Emory University; Koleka Mlisana, University of KwaZulu-Natal; Pravi Moodley, University of KwaZulu-Natal; Brent A. Johnson, University of Rochester; Salim Allana, Emory University; Angela Campbell, Emory University; Kristin Nelson, Emory University; Iqbal Master, King Dinuzulu Hospital; James C.M. Brust, Albert Einstein College of Medicine and Montefiore Medical Center
• Language: English
• Date: 2020-01-01
• Publisher: LIPPINCOTT WILLIAMS & WILKINS
• Publication Version: Author Accepted Manuscript (After Peer Review)
• Copyright Statement: 2020
• License: Creative Commons Attribution-NonCommercial 4.0 International
• Final Published Version (URL): http://dx.doi.org/10.1097/QAI.0000000000002190
• Title of Journal or Parent Work: JAIDS-JOURNAL OF ACQUIRED IMMUNE DEFICIENCY SYNDROMES
• Volume: 83
• Issue: 1
• Start Page: 47
• End Page: 55
• Grant/Funding Information: This study was funded by the US National Institute of Allergy and Infectious Diseases (NIAID), National Institutes of Health (NIH): R01AI087465 and R01AI089349 (both to NRG). It was also supported in part by NIH/NIAID grants: R01AI114304 (to JCMB), K24AI114444 (to NRG), Emory Center for AIDS Research (CFAR) P30AI050409, Einstein-Rockefeller-CUNY CFAR P30AI124414, Emory TB Research Unit (TBRU) U19AI111211, Einstein/Montefiore Institute for Clinical and Translational Research (ICTR) UL1TR001073 and the Georgia Clinical and Translational Science Alliance UL1TR002378.
• Keywords: Science & Technology; HIV; MDR-TB; OUTCOMES; Immunology; Life Sciences & Biomedicine; HEARING-LOSS; TESTS; MODEL; side effects; toxicity; MULTIDRUG-RESISTANT TUBERCULOSIS; adverse events; ETHAMBUTOL; Infectious Diseases
• Research Categories: Health Sciences, Epidemiology; Health Sciences, Public Health; Health Sciences, Immunology

Abstract

Background:South Africa has among the highest incidence of multidrug-resistant tuberculosis (MDR-TB) and more than 70% of patients are HIV co-infected. MDR-TB treatment is associated with frequent adverse events (AEs). Although guidelines recommend concurrent treatment of MDR-TB and HIV, safety data on concurrent therapy are limited.Methods:We conducted a prospective observational study of MDR-TB patients with and without HIV-coinfection in South Africa between 2011 and 2015. Participants received standardized MDR-TB and HIV regimens. Participants were followed monthly for the duration of MDR-TB therapy and screened for clinical and laboratory AEs. Audiometry was performed monthly during the intensive phase; color discrimination testing was performed every 2 months.Results:We enrolled 150 HIV-infected and 56 HIV-uninfected participants. Nearly all experienced at least one clinical (93%) or laboratory (96%) AE. The most common clinical AEs were peripheral neuropathy (50%) and difficulty sleeping (48%); the most common laboratory AEs were hypokalemia (47%) and decreased creatinine clearance (46%). Among 19 clinical and lab AEs examined, there were no differences by HIV status, except for diarrhea (27% HIV-infected vs. 13% HIV-uninfected, P = 0.03). Hearing loss was experienced by 72% of participants (8% severe loss). Fourteen percent experienced color discrimination loss (4% severe loss). There were no differences in frequency or severity of hearing or vision loss by HIV status.Conclusions:AEs were common, but not more frequent or severe among MDR-TB/HIV co-infected participants receiving concurrent antiretroviral therapy. Given the favorable treatment outcomes associated with concurrent treatment, antiretroviral therapy initiation should not be delayed in MDR-TB patients with HIV-coinfection.