title: Hepatotoxicity in patients co-infected with tuberculosis and HIV-1 while receiving non-nucleoside reverse transcriptase inhibitor-based antiretroviral therapy and rifampicin-containing anti-tuberculosis regimen.
abstract: To evaluate the rate of and risk factors for hepatotoxicity in tuberculosis (TB) and human immunodeficiency virus type 1 (HIV-1) co-infected patients while receiving non-nucleoside reverse transcriptase inhibitor (NNRTI)-based antiretroviral therapy (ART) and a rifampicin (RMP)-containing anti-TB regimen. We analyzed data from the N2R study which was an open label, randomized, comparative trial comparing treatment outcomes between 71 TB/HIV-1 co-infected patients receiving efavirenz (EFV)-based and nevirapine (NVP)-based ART; all of whom were receiving RMP-containing anti-TB treatment. Demographic data, liver function test, CD4 cell count, plasma HIV-1 RNA, hepatitis B surface antigen and anti-hepatitis C virus antibody were collected before initiating ART (week 0). Liver enzymes and total bilirubin levels were monitored at 6 weeks, 12 weeks and 24 weeks after ART initiation. All patients were followed until TB therapy was completed. Of 142 patients, 8 patients were excluded. Among the remaining 134 patients, the mean+/-SD age was 36.8+/-8.6 years and 67.2% were male. Severe hepatotoxicity (grade 3 or 4) developed in 4 patients (2.9%); 3 patients (4.6%) in the NVP group and 1 patient (1.4%) in the EFV group. Severe hyperbilirubinemia (grade 3 or 4) occurred in 7 patients (5.2%); 5 patients (7.7%) in the NVP group and 2 patients (2.9%) in the EFV group. Grade 1 or 2 hepatotoxicity occurred in 34 patients (31.4%). Hepatitis C virus co-infection (adjusted OR 3.03; 95%CI 1.26-7.29) was an independent risk factor associated with grade 1-4 hepatotoxicity (p=0.013). Monitoring of hepatotoxicity should be considered in TB/HIV-1 co-infected patients who are infected with HCV and receiving NVP.
authors.affiliation: Bamrasnaradura Infectious Diseases Institute, Ministry of Public Health, Nonthaburi, Thailand. mwiroj@yahoo.com
authors.forename: Wiroj
authors.initials: W
authors.lastname: Mankhatitham
authors.forename: Aroon
authors.initials: A
authors.lastname: Lueangniyomkul
authors.forename: Weerawat
authors.initials: W
authors.lastname: Manosuthi
mesh_terms: D000328:Adult; D000480:Alkynes; D000904:Antibiotics, Antitubercular / Q000009:adverse effects* / Q000627:therapeutic use; D048588:Benzoxazines / Q000009:adverse effects; D056486:Chemical and Drug Induced Liver Injury / Q000453:epidemiology*; D003521:Cyclopropanes; D005260:Female; D015658:HIV Infections / Q000150:complications* / Q000188:drug therapy; D015497:HIV-1; D006801:Humans; D006932:Hyperbilirubinemia / Q000139:chemically induced / Q000453:epidemiology; D008111:Liver Function Tests; D016015:Logistic Models; D008297:Male; D008875:Middle Aged; D019829:Nevirapine / Q000009:adverse effects; D018894:Reverse Transcriptase Inhibitors / Q000009:adverse effects*; D012293:Rifampin / Q000009:adverse effects / Q000627:therapeutic use; D012307:Risk Factors; D013785:Thailand / Q000453:epidemiology; D014376:Tuberculosis / Q000150:complications* / Q000188:drug therapy; D055815:Young Adult
chemical_list: D000480:Alkynes; D000904:Antibiotics, Antitubercular; D048588:Benzoxazines; D003521:Cyclopropanes; D018894:Reverse Transcriptase Inhibitors; D019829:Nevirapine; C098320:efavirenz; D012293:Rifampin