Date Published: March 9, 2012
Publisher: BioMed Central
Author(s): Anchalee Avihingsanon, Gail V Matthews, Sharon R Lewin, Pip Marks, Jose Sasadeusz, David A Cooper, Scott Bowden, Stephen Locarnini, Greg J Dore, Kiat Ruxrungtham.
Hepatotoxicity (HT) after HAART initiation has been reported in 2-14% of HIV positive individuals [1-3], and the risk increases significantly in HBV or HCV coinfected individuals [1,4]. Definitions of HT vary but the most commonly used is based on the AIDS Clinical Trial Group (ACTG) criteria in which an increase in ALT and/or AST above 5 × upper limit of normal (ULN) (Grade 3) is defined as severe HT. HF (HF) appears to be particularly common within the first months after HAART initiation, suggesting a potential immunological component to its development. The outcome following HF may be beneficial with subsequent serological change; on the other it may also be associated with morbidity, and even mortality. Although, HF after initiation of HAART in HIV-HBV coinfected individuals is well recognized, prospective data on predictors and subsequent outcome are limited.
Full eligibility criteria for this study are given elsewhere , but in brief, subjects were HIV-1 antibody positive and naïve to ARV with chronic hepatitis B infection (HBV surface antigen (HBsAg)-positive > 6 months apart with HBV DNA > 100,000 copies/mL). Subjects were excluded if they had evidence of other causes for chronic liver disease ie hepatitis C virus, acute hepatitis A virus, autoimmune disease, serum ALT level > 1000 IU/L. Early HF was defined as ALT > 5 × ULN during the first 12 weeks.
Thirty-six advanced HIV/HBV co-infected patients with a median CD4 count of 36 cells/mm3 (interquartile range (IQR) 19-208 cells/mm3) and HIV RNA of 4.7 log10 c/ml (IQR 4.3-5.1 log10 c/ml) were enrolled. HBV DNA was high at baseline (median 8.4 log10 c/ml, IQR 8.1-9.5 log10 c/ml), 61% of the group were HBeAg positive and 53% had normal baseline ALT. Twenty-nine patients (81%) were infected with HBV genotype C. Seven (19%) had experienced a prior AIDS defining illness, six (17%) were on isoniazid and rifampicin for tuberculous treatment. Twenty-four (67%) and 58% were on co-trimoxazole and fluconazole, respectively, for opportunistic infection (OI) prophylaxis.
EHF after HBV active HAART initiation was frequently observed in this population.
The rate of HF is high during the first 12 weeks of HBV-active HAART initiation in an advanced immunodeficient Asian population. Although the mechanisms underlying this may be multifactorial, our findings most strongly support a significant role for HBV immune restoration disease as the major contributing factor. A strategy of short-course lead-in anti-HBV therapy (using drugs without anti-HIV activity) could be studied as a potential mechanism to decrease HBV burden and prevent HF after HAART initiation in such individuals.
The Kirby Institute for infection and immunity in society is funded by the Australian Government Department of Health & Ageing and is affiliated with the Faculty of Medicine, The University of New South Wales. KR and Vaccine & Cellular Immunology Laboratory are partly funded by the Research-team Strengthening Grant, National Center for Genetic Engineering and Biotechnology (BIOTEC), Thailand. Other authors declare that they have no competing interests.
All authors participated in the design of the study. AA and GVM drafted the manuscript. JS, SC and SL performed the laboratory tests. SRL, PM, DAC, GJD and KR reviewed the paper. All authors have seen and approved the final manuscript.