title: Concomitant use of nonnucleoside analogue reverse transcriptase inhibitors and rifampicin in TB/HIV type 1-coinfected patients.
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.
authors.affiliation: Imperial College Healthcare NHS Trust, London W21NY, UK. upali.sathia@imperial.nhs.uk
authors.forename: Leena
authors.initials: L
authors.lastname: Sathia
authors.forename: Ifeyinwa
authors.initials: I
authors.lastname: Obiorah
authors.forename: Graham
authors.initials: G
authors.lastname: Taylor
authors.forename: Onn
authors.initials: O
authors.lastname: Kon
authors.forename: Marie
authors.initials: M
authors.lastname: O'Donoghue
authors.forename: Sara
authors.initials: S
authors.lastname: Gibbins
authors.forename: John
authors.initials: J
authors.lastname: Walsh
authors.forename: Alan
authors.initials: A
authors.lastname: Winston
mesh_terms: D000328:Adult; D000480:Alkynes; D000904:Antibiotics, Antitubercular / Q000627:therapeutic use*; D023241:Antiretroviral Therapy, Highly Active; D048588:Benzoxazines / Q000493:pharmacokinetics / Q000627:therapeutic use*; D056486:Chemical and Drug Induced Liver Injury / Q000517:prevention & control; D003521:Cyclopropanes; D004334:Drug Administration Schedule; D016903:Drug Monitoring; D005260:Female; D015658:HIV Infections / Q000150:complications / Q000188:drug therapy* / Q000378:metabolism; D015497:HIV-1; D006801:Humans; D008297:Male; D019829:Nevirapine / Q000493:pharmacokinetics / Q000627:therapeutic use*; D011446:Prospective Studies; D018894:Reverse Transcriptase Inhibitors / Q000493:pharmacokinetics / Q000627:therapeutic use*; D012293:Rifampin / Q000627:therapeutic use*; D016896:Treatment Outcome; D014376:Tuberculosis / Q000188:drug therapy*
chemical_list: D000480:Alkynes; D000904:Antibiotics, Antitubercular; D048588:Benzoxazines; D003521:Cyclopropanes; D018894:Reverse Transcriptase Inhibitors; D019829:Nevirapine; C098320:efavirenz; D012293:Rifampin