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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.

Author information

1
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.
2
Medical Research Council-CAPRISA HIV-TB Pathogenesis and Treatment Research Unit, Doris Duke Medical Research Institute Durban, South Africa.
3
Department of Pulmonology and Critical Care, Groote Schuur Hospital, University of Cape Town, South Africa.
4
Department of Health Policy and Management, Mailman School of Public Health, Columbia University, New York City, NY.
5
Department of Infectious Diseases, Division of Internal Medicine, Greys Hospital, KwaZulu-Natal, South Africa.
6
Drug-resistant TB Unit, King Dinizulu Hospital, KwaZulu-Natal, South Africa.

Abstract

BACKGROUND:

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

METHODS:

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.

RESULTS:

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).

CONCLUSIONS:

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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