Effect of HIV co-infection on mutation patterns of HBV in patients with lamivudine-resistant chronic hepatitis B.
A retrospective review was performed comparing lamivudine-resistance mutation patterns between patients infected with hepatitis B virus (HBV) with or without human immunodeficiency virus (HIV) co-infection. Medical records that included a genotypic test of patients infected with HBV and treated with lamivudine as the only anti-HBV drug were reviewed. Pol gene mutations were assessed by direct sequencing of the reverse transcriptase fragment 125-213 aa. Eighty-nine patients infected with HBV (29 co-infected with HIV) with rtM204V or rtM204I mutations were included. Multiple mutations associated with the YMDD motif were observed in 33 (55%) of 60 patients infected with HBV only and in 28 (96.6%) of patients co-infected with HIV/HBV. In this latter group, the prevalence of the rtV173L + rtL180M + rtM204V triple mutation was 31% versus a prevalence of 3.4% observed among patients infected with HBV only. All patients with the triple mutational pattern showed sE164D + sI195M changes in the envelope gene. Multivariate analysis demonstrated that HIV co-infection (adjusted OR 11.2, 95% CI 2.0-61.0) and HBV genotype A (adjusted OR 7.2, 95% CI 1.5-34.8) were the only independent variables associated with the chance of harboring rtM204V. Patients with HBV genotype A or HIV co-infection were more likely to harbor the rtM204V mutation. Patients co-infected with HIV showed multiple mutations more frequently, including the triple mutation that may elicit a vaccine escape phenotype. Among patients co-infected with HIV/HBV, strict HBV DNA monitoring is essential to detect treatment failure and adapt therapy to avoid limitations of future therapeutic options or the emergence of a public health threat.
Iacomi
Fabio
F
Clinical Department of Infectious Diseases, National Institute for Infectious Disease, L. Spallanzani, Rome, Italy.
Vincenti
Donatella
D
Vairo
Francesco
F
Solmone
Mariacarmela
M
Mariano
Andrea
A
Piselli
Pierluca
P
Puro
Vincenzo
V
Capobianchi
Maria Rosaria
MR
Antonucci
Giorgio
G
D000328:Adult; D000998:Antiviral Agents / Q000627:therapeutic use*; D004279:DNA, Viral / Q000235:genetics; D024882:Drug Resistance, Viral; D005260:Female; D015686:Gene Products, env / Q000235:genetics; D015684:Gene Products, pol / Q000235:genetics; D015658:HIV Infections / Q000150:complications* / Q000188:drug therapy*; D006515:Hepatitis B virus / Q000235:genetics*; D019694:Hepatitis B, Chronic / Q000821:virology*; D006801:Humans; D019259:Lamivudine / Q000627:therapeutic use*; D008297:Male; D008875:Middle Aged; D020125:Mutation, Missense; D012189:Retrospective Studies; D017422:Sequence Analysis, DNA
D000998:Antiviral Agents; D004279:DNA, Viral; D015686:Gene Products, env; D015684:Gene Products, pol; D019259:Lamivudine