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J Acquir Immune Defic Syndr. 2018 Aug 15;78(5):536-542. doi: 10.1097/QAI.0000000000001705.

Risk of Nephrotoxicity in Patients With Drug-Resistant Tuberculosis Treated With Kanamycin/Capreomycin With or Without Concomitant Use of Tenofovir-Containing Antiretroviral Therapy.

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Centre for the AIDS Programme of Research in South Africa, Nelson R Mandela School of Medicine, College of Health Sciences, University of KwaZulu-Natal, Durban, South Africa.
Medical Research Council-CAPRISA HIV-TB Pathogenesis and Treatment Research Unit, Doris Duke Medical Research Institute Durban, South Africa.
Department of Pulmonology and Critical Care, Groote Schuur Hospital, University of Cape Town, South Africa.
Department of Health Policy and Management, Mailman School of Public Health, Columbia University, New York City, NY.
Department of Infectious Diseases, Division of Internal Medicine, Greys Hospital, KwaZulu-Natal, South Africa.
Drug-resistant TB Unit, King Dinizulu Hospital, KwaZulu-Natal, South Africa.



The intersection of HIV and drug-resistant (DR) tuberculosis (TB) presents the challenge of managing convergent drug toxicities.


We conducted a retrospective study of adult patients with DR-TB treated with a kanamycin/capreomycin-based (KM) regimen, with or without concomitant antiretroviral therapy (ART). We estimated the incidence of nephrotoxicity (defined as an increase in serum creatinine greater than 26.5 ┬Ámol, or an increase in serum creatinine to 1.5 times the baseline value, or a decline in glomerular filtration rate to less than 60 mL/min/1.73 m), and evaluated the association between reported drug use and nephrotoxicity using Kaplan-Meier plots.


A total of 215 patients with DR-TB were treated with a kanamycin/capreomycin-based regimen, with or without concomitant ART. The incidence rate of nephrotoxicity was 3.6 [95% confidence interval (CI): 1.4 to 7.3], 6.9 (95% CI: 5.2 to 9.0), and 12 (95% CI: 3.3 to 30.9) cases per 100 person-months of follow-up in the KM only group (n = 42), the KM + TDF (tenofovir disoproxil fumarate) group (n = 163), and the KM + Other ART group (n = 10), respectively. Using the KM only group as a reference, the hazard ratio was 2.06 (95% CI: 0.92 to 4.63) in the KM + TDF group, and 4.09 (95% CI: 1.17 to 14.25) in the KM + Other ART group. Advancing age was an independent predictor of nephrotoxicity (adjusted hazard ratio 1.29, 95% CI: 1.14 to 1.46).


Our findings provide evidence of a significant risk of nephrotoxicity during treatment with a kanamycin/capreomycin-based DR-TB regimen, with or without concurrent treatment with ART. This study lends further support to calls for the substitution of TDF during the intensive phase of DR-TB treatment and for close monitoring of renal function during DR-TB treatment, especially in settings where the use of kanamycin/capreomycin is unavoidable.

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