N Padayatchi1, M Gopal2, R Naidoo3, L Werner3, K Naidoo3, I Master4, M R O'Donnell5. 1. Centre for the AIDS Programme of Research in South Africa (CAPRISA), Nelson R. Mandela School of Medicine, Doris Duke Medical Research Institute, University of KwaZulu-Natal, Private Bag X7, Congella, 4013, South Africa padayatchin@ukzn.ac.za. 2. Gulf Coast Pulmonary Medicine, Port Charlotte, FL 33952, USA. 3. Centre for the AIDS Programme of Research in South Africa (CAPRISA), Nelson R. Mandela School of Medicine, Doris Duke Medical Research Institute, University of KwaZulu-Natal, Private Bag X7, Congella, 4013, South Africa. 4. King Dinuzulu Hospital, PO Box Dormerton 4015, South Africa. 5. Centre for the AIDS Programme of Research in South Africa (CAPRISA), Nelson R. Mandela School of Medicine, Doris Duke Medical Research Institute, University of KwaZulu-Natal, Private Bag X7, Congella, 4013, South Africa Division of Pulmonary Medicine, Department of Internal Medicine, Montefiore Medical Center, Albert Einstein College of Medicine, 1300 Morris Park Avenue, Bronx, NY 10461, USA.
Abstract
BACKGROUND: Extensively drug-resistant (XDR) tuberculosis (TB) and HIV coinfection is associated with low cure rates and high mortality. Clofazimine has shown activity in vitro against Mycobacterium tuberculosis, but clinical experience with clofazimine in XDR-TB and HIV coinfection is limited. METHODS: This was a retrospective cohort study of adult XDR-TB patients in KwaZulu-Natal, South Africa, treated with either a clofazimine- or non-clofazimine-containing XDR-TB treatment regimen. The primary outcome measure was TB culture conversion at 6 months. Survival analysis and multivariate logistic regression compared time to event in different strata and identified risk factors for TB culture conversion. RESULTS: Between August 2009 and July 2011, eligible XDR-TB patients (n = 85) were initiated on treatment for XDR-TB. Most patients (86%) were HIV-infected and receiving antiretroviral therapy (90%). Patients receiving a clofazimine-containing regimen (n = 50) had a higher percentage of culture conversion (40%) compared with patients (n = 35) receiving a non-clofazimine regimen (28.6%). On multivariate analysis, there was a 2-fold increase in TB culture conversion at 6 months (hazard rate ratio 2.54, 95% CI 0.99-6.52, P = 0.05) in the group receiving a clofazimine-containing regimen. Adverse effects due to clofazimine were minor and rarely life-threatening. CONCLUSIONS: Clofazimine was associated with improved culture conversion in the treatment of XDR-TB/HIV. Adverse effects were minor and non-life-threatening. Based on these preliminary data, further study of clofazimine in XDR-TB/HIV treatment is warranted. Given the present low rates of culture conversion in XDR-TB treatment, we recommend empirical inclusion of clofazimine in treatment regimens for XDR-TB.
BACKGROUND: Extensively drug-resistant (XDR) tuberculosis (TB) and HIV coinfection is associated with low cure rates and high mortality. Clofazimine has shown activity in vitro against Mycobacterium tuberculosis, but clinical experience with clofazimine in XDR-TB and HIV coinfection is limited. METHODS: This was a retrospective cohort study of adult XDR-TBpatients in KwaZulu-Natal, South Africa, treated with either a clofazimine- or non-clofazimine-containing XDR-TB treatment regimen. The primary outcome measure was TB culture conversion at 6 months. Survival analysis and multivariate logistic regression compared time to event in different strata and identified risk factors for TB culture conversion. RESULTS: Between August 2009 and July 2011, eligible XDR-TBpatients (n = 85) were initiated on treatment for XDR-TB. Most patients (86%) were HIV-infected and receiving antiretroviral therapy (90%). Patients receiving a clofazimine-containing regimen (n = 50) had a higher percentage of culture conversion (40%) compared with patients (n = 35) receiving a non-clofazimine regimen (28.6%). On multivariate analysis, there was a 2-fold increase in TB culture conversion at 6 months (hazard rate ratio 2.54, 95% CI 0.99-6.52, P = 0.05) in the group receiving a clofazimine-containing regimen. Adverse effects due to clofazimine were minor and rarely life-threatening. CONCLUSIONS:Clofazimine was associated with improved culture conversion in the treatment of XDR-TB/HIV. Adverse effects were minor and non-life-threatening. Based on these preliminary data, further study of clofazimine in XDR-TB/HIV treatment is warranted. Given the present low rates of culture conversion in XDR-TB treatment, we recommend empirical inclusion of clofazimine in treatment regimens for XDR-TB.
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