1. Concomitant use of nonnucleoside analogue reverse transcriptase inhibitors and rifampicin in TB/HIV type 1-coinfected patients.
- Author
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Sathia L, Obiorah I, Taylor G, Kon O, O'Donoghue M, Gibbins S, Walsh J, and Winston A
- Subjects
- Adult, Alkynes, Antiretroviral Therapy, Highly Active, Benzoxazines pharmacokinetics, Chemical and Drug Induced Liver Injury prevention & control, Cyclopropanes, Drug Administration Schedule, Drug Monitoring, Female, HIV Infections complications, HIV Infections metabolism, Humans, Male, Nevirapine pharmacokinetics, Prospective Studies, Reverse Transcriptase Inhibitors pharmacokinetics, Treatment Outcome, Antibiotics, Antitubercular therapeutic use, Benzoxazines therapeutic use, HIV Infections drug therapy, HIV-1, Nevirapine therapeutic use, Reverse Transcriptase Inhibitors therapeutic use, Rifampin therapeutic use, Tuberculosis drug therapy
- Abstract
Pharmacokinetic interactions between rifampicin and nonnucleoside analogue reverse transcriptase inhibitors (NNRTIs) pose challenges in the treatment of TB/HIV coinfection. We describe NNRTI plasma concentrations (PC) and treatment outcomes in TB/HIV coinfected patients receiving rifampicin and NNRTIs concomitantly. Single center prospective data were collected on all TB/HIV-coinfected patients who received concomitant NNRTI and rifampicin between 2001 and 2005. Of 103 TB/HIV coinfected patients, 26 received concomitant rifampicin with efavirenz (EFV) and 17 with nevirapine (NVP). NNRTIs were commenced after rifampicin in 18/26 (69%) and 7/17 (41%) subjects treated with EFV and NVP, respectively. Of these 88% completed antituberculosis therapy. There were two (5%) deaths, both due to lymphoproliferative malignancy. Three (7%) patients transferred care or discontinued therapy. Of subjects 83% had normal liver function tests (LFTs) and 11% had Grade 1-2 and 6% Grade 3-4 LFT abnormalities during concomitant therapy. PCs were measured in 31 patients. The first PCs were within the therapeutic range in 5/7 on NVP 200 mg bd, 2/4 on NVP 300 mg bd, 3/7 EFV 600 mg od, and 7/13 on EFV 800 mg od. PCs were subtherapeutic in 4/11 (36%) and 3/20 (20%) subjects on NVP and EFV, respectively. No virological rebounds were observed. Of subjects receiving concomitant NVP or EFV with rifampicin, 64% and 80%, respectively, had therapeutic NNRTI PCs. Subtherapeutic PCs were not associated with virological failure. Good clinical outcomes and a low incidence of hepatotoxicity were observed.
- Published
- 2008
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