Journal
AIDS
Volume 20, Issue 6, Pages 863-870Publisher
LIPPINCOTT WILLIAMS & WILKINS
DOI: 10.1097/01.aids.0000218550.85081.59
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Funding
- NCRR NIH HHS [5-M01-RR-00722] Funding Source: Medline
- NIAID NIH HHS [UO1-AI-37613, UO1-AI-37984, UO1-AI-35040, R01AI060449, UO1-AI-35042, UO1-AI-35039, UO1-AI-35043] Funding Source: Medline
- NIDA NIH HHS [K08DA00441] Funding Source: Medline
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Background: Little is known about the prevalence and pattern of hepatitis B virus (HBV) mutations in HIV/HBV co-infected individuals on long-term lamivudine (3TC) therapy. Methods: HBV polymerase/envelope/basal core promoter/pre-core sequences from 81 HIV-HBV co-infected persons who received at least 6 months 3TC were compared to HBV reference sequences. Host and viral characteristics associated with HBV mutations were determined. Results: HBV viraemia was detected in 53 persons (65%) and was associated with lower CD4 cell count nadir and higher HIV RNA at the time of testing but not with 3TC duration. Known 3TC-resistant mutations occurred in 50% and 94% of viremic patients with < 2 years and > 4 years 3TC, respectively. The CD4 cell count at testing was significantly higher in those with 3TC-resistant mutations. The triple polymerase mutant (rtL173V, rtL180M, rtM204V), which behaves as a vaccine escape mutant in vitro, occurred in 17% of viraemic patients. Polymerase mutations that may confer resistance to other anti-HBV agents were also detected. Conclusions: In HIV-HBV co-infected patients, greater immunocompromise is associated with continued HBV viraemia while on 3TC, and development of 3TC-resistant mutations are inevitable with prolonged 3TC use. These Mutant viruses may limit future therapeutic options due to cross-resistance or may produce HBV vaccine escape mutants. Thus, timing and selection of antiretroviral therapy is critical in this population. (C) 2006 Lippincott Williams & Wilkins.
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