Hepatotoxicity in an African antiretroviral therapy cohort: the effect of tuberculosis and hepatitis B

• Published in: AIDS (London) Vol. 21; no. 10; pp. 1301 - 1308
• Main Authors: Hoffmann, Christopher J, Charalambous, Salome, Thio, Chloe L, Martin, Desmond J, Pemba, Lindiwe, Fielding, Katherine L, Churchyard, Gavin J, Chaisson, Richard E, Grant, Alison D
• Format: Journal Article
• Language: English
• Published: Hagerstown, MD Lippincott Williams & Wilkins 19.06.2007
• Subjects: Adult; Alanine Transaminase - analysis; Anti-HIV Agents - administration & dosage; Anti-HIV Agents - adverse effects; Antibiotics. Antiinfectious agents. Antiparasitic agents; Antitubercular Agents - therapeutic use; Antiviral agents; Aspartate Aminotransferases - analysis; Biological and medical sciences; Chemical and Drug Induced Liver Injury; Drug Therapy, Combination; Drug toxicity and drugs side effects treatment; Female; Hepatitis B - immunology; Hepatitis B Surface Antigens - blood; HIV Infections - complications; HIV Infections - drug therapy; HIV Infections - immunology; Human immunodeficiency virus; Human viral diseases; Humans; Incidence; Infectious diseases; Liver - drug effects; Liver - enzymology; Male; Medical sciences; Middle Aged; Mycobacterium; Occupational Diseases - drug therapy; Occupational Diseases - epidemiology; Occupational Diseases - immunology; Pharmacology. Drug treatments; Retrospective Studies; South Africa - epidemiology; Toxicity: digestive system; Treatment Outcome; Tuberculosis - complications; Tuberculosis - drug therapy; Tuberculosis - epidemiology; Viral diseases; Viral diseases of the lymphoid tissue and the blood. Aids; South Africa; Africa; Antiretroviral agent; Benzoxazine derivatives; RNA-directed DNA polymerase; Acetylenic compound; Toxicity; hepatitis B; Non nucleoside compound; toxic hepatitis; Hepatic disease; Mycobacterial infection; Efavirenz; Viral hepatitis B; Reverse transcriptase inhibitor; Nucleoside analog; Antiviral; Pyrimidine nucleoside; Hepatotoxicity; Viral hepatitis C; Immunopathology; Alanine; Enzyme; Transferases; Enzyme inhibitor; Lamivudine; AIDS; Immune deficiency; Infection; Allosteric inhibitor; Nucleotidyltransferases; Chemotherapy; Treatment; Tuberculosis; HIV; Aminoacid; Dideoxynucleoside; Viral disease; Bacteriosis; Digestive diseases; Zidovudine; HAART
• ISSN: 0269-9370
• DOI: 10.1097/QAD.0b013e32814e6b08

Hepatotoxicity is a significant complication of antiretroviral therapy (ART). We assessed the incidence of and risk factors for hepatotoxicity among HIV-infected individuals on ART in South Africa. We conducted a retrospective cohort study in a workplace HIV care program in South Africa which uses a first-line regimen of efavirenz, zidovudine, and lamivudine and provides routine clinical and laboratory monitoring. We included subjects with baseline and follow-up alanine transaminase and aspartate aminotransferase tests. Severe hepatotoxicity cases were identified during the first 12 months of ART. Potential risk factors, including concomitant medication use, tuberculosis, and hepatitis B and C, were determined from clinical records, database queries, and serological testing. Associations with hepatotoxicity were investigated using Cox proportional hazards modeling. Of the 868 subjects (94% male, median age 41 years), the median nadir CD4 cell count was 136/microl, 25% received concomitant tuberculosis treatment during ART, and 17% of a randomly selected subset were positive for hepatitis B surface antigen (HBsAg). We identified 7.7 episodes of severe hepatotoxicity per 100 person-years. Tuberculosis treatment increased risk 8.5 fold, positive HBsAg 3.0 fold, and nadir CD4 cells count < 100/microl 1.9 fold. Importantly, the fraction of patients with severe hepatotoxicity on ART (4.6%) was similar to the fraction with liver enzyme elevations > 5 times the upper limit of normal before starting ART (4%). In this African ART cohort, we found a low incidence of and minimal morbidity due to hepatotoxicity. HBsAg and concomitant tuberculosis therapy significantly increased the risk of hepatotoxicity.