title: Nevirapine-associated early hepatotoxicity: incidence, risk factors, and associated mortality in a primary care ART programme in South Africa.
abstract: BACKGROUND
  The majority of antiretroviral treatment programmes in sub-Saharan Africa are scaling up antiretroviral treatment using a fixed dose first-line antiretroviral regimen containing stavudine, lamivudine, and nevirapine. One of the primary concerns with the use of this regimen is nevirapine-associated hepatotoxicity.
  
  
  RESULTS
  Study participants were 1809 HIV-infected, antiretroviral naïve adults initiating nevirapine-based antiretroviral therapy between November 2002 and December 2006. The primary outcome was early hepatotoxicity. Secondary outcomes were associations with hepatotoxicity and mortality at six months. The cumulative proportion of early hepatotoxicity ranged from 1.0-2.0% giving an incidence-rate at 102 days of 3.6-7.6 per 100 person-years. Median time to hepatotoxicity was 32 (IQR 28-58) days. At 12 weeks, only 8% of patients had alanine aminotransferase monitoring at all the time-points recommended by national guidelines. No association was found between age, gender, baseline CD4 count, concurrent tuberculosis infection, prior participation in a prevention of mother-to-child-transmission program, or baseline weight and early hepatotoxicity. There was no association between early hepatotoxicity and mortality.
  
  
  CONCLUSIONS
  The cumulative proportion of early hepatotoxicity in nevirapine based antiretroviral therapy was low in this resource-constrained setting. Hepatotoxicity was not associated with mortality. Frequent routine monitoring of alanine aminotransferase proved difficult to implement in this public sector primary care programme. Focused monitoring in the first month may be a more cost-effective and pragmatic option in settings with limited resources. Correlation with clinical signs and symptoms may allow future alanine aminotransferase testing to be dictated by clinical criteria.
authors.affiliation: South African Medical Unit, Médecins Sans Frontières, Johannesburg, South Africa. kathryn.chu@joburg.msf.org
authors.forename: Kathryn M
authors.initials: KM
authors.lastname: Chu
authors.forename: Andrew M
authors.initials: AM
authors.lastname: Boulle
authors.forename: Nathan
authors.initials: N
authors.lastname: Ford
authors.forename: Eric
authors.initials: E
authors.lastname: Goemaere
authors.forename: Valerie
authors.initials: V
authors.lastname: Asselman
authors.forename: Gilles
authors.initials: G
authors.lastname: Van Cutsem
mesh_terms: D000328:Adult; D000410:Alanine Transaminase / Q000097:blood; D023241:Antiretroviral Therapy, Highly Active / Q000009:adverse effects; D018791:CD4 Lymphocyte Count; D056486:Chemical and Drug Induced Liver Injury / Q000097:blood / Q000209:etiology* / Q000401:mortality; D005260:Female; D005500:Follow-Up Studies; D015658:HIV Infections / Q000188:drug therapy*; D006801:Humans; D015994:Incidence; D008099:Liver / Q000187:drug effects* / Q000473:pathology; D008297:Male; D015999:Multivariate Analysis; D019829:Nevirapine / Q000009:adverse effects* / Q000627:therapeutic use; D011320:Primary Health Care / Q000379:methods; D018894:Reverse Transcriptase Inhibitors / Q000009:adverse effects / Q000627:therapeutic use; D012307:Risk Factors; D013019:South Africa / Q000453:epidemiology; D015996:Survival Rate; D013997:Time Factors
chemical_list: D018894:Reverse Transcriptase Inhibitors; D019829:Nevirapine; D000410:Alanine Transaminase