title: The prevalence and risk of hepatitis flares in a Serbian cohort of HIV and HCV co-infected patients treated with HAART.
abstract: Despite substantial benefits of HAART treatment of HIV-infected patients, cumulative long-term toxicity, including drug-induced hepatotoxicity, has emerged as an important complication. Thus, to examine the prevalence and risk of developing severe hepatic injury during HAART, we conducted a retrospective study in a cohort of 364 HIV-infected patients treated with HAART between January 1998 and May 2006, for whom data on alanine aminotransferase activity were available both before and during HAART. HCV co-infection was recorded in 35.4% of the series, but was found not to influence either the efficacy of HAART or survival (P>0.05). Severe hepatotoxicity occurred in a total of 24 patients (6.6%). Multivariate logistic regression defined HCV co-infection (OR 16.6, 95% CI 3.8-46.0, P<0.0001), and the use of SQV/RTV and d4T (OR 3.1, 95% CI 1.2-8.16, P=0.02, and OR 7.1, 95% CI 1.0-54.5, P=0.05, respectively) as independent risk factors for aggravation of hepatitis. In addition, there was a significant increase in the probability of developing liver damage over years of treatment (Log rank, P<0.01). Conversely, the probability of developing hepatotoxicity was not associated with an increase in the CD4 cell count to values greater than 350/microL (Log rank, P=0.59). In conclusion, in the setting of chronic viral hepatitis, hepatotoxicity during HAART may be attributed to the cumulative toxicity of drugs that induce mitochondrial toxicity, along with particular PIs and/or NNRTIs. Furthermore, our data suggest prudent use of D-drugs, still common in resource-limited countries, in HCV co-infected patients.
authors.affiliation: HIV/AIDS Department, Institute for Infectious & Tropical Diseases, Clinical Centre of Serbia, Belgrade University School of Medicine, Bulevar Oslobodjenja 16, 11000 Belgrade, Serbia. djordjejevtovic@hotmail.com
authors.forename: Dj
authors.initials: Dj
authors.lastname: Jevtović
authors.forename: J
authors.initials: J
authors.lastname: Ranin
authors.forename: D
authors.initials: D
authors.lastname: Salemović
authors.forename: I
authors.initials: I
authors.lastname: Pesić
authors.forename: G
authors.initials: G
authors.lastname: Dragović
authors.forename: S
authors.initials: S
authors.lastname: Zerjav
authors.forename: O
authors.initials: O
authors.lastname: Djurković-Djaković
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D023241:Antiretroviral Therapy, Highly Active / Q000009:adverse effects*; D018791:CD4 Lymphocyte Count; D005260:Female; D005500:Follow-Up Studies; D015658:HIV Infections / Q000150:complications / Q000188:drug therapy*; D019698:Hepatitis C, Chronic / Q000150:complications* / Q000473:pathology; D006801:Humans; D008099:Liver / Q000187:drug effects / Q000473:pathology; D008111:Liver Function Tests; D016015:Logistic Models; D008297:Male; D008875:Middle Aged; D015995:Prevalence; D012189:Retrospective Studies; D012307:Risk Factors; D019438:Ritonavir / Q000009:adverse effects; D019258:Saquinavir / Q000009:adverse effects; D018119:Stavudine / Q000009:adverse effects; D015996:Survival Rate; D013997:Time Factors; D015022:Yugoslavia
chemical_list: D018119:Stavudine; D019258:Saquinavir; D019438:Ritonavir