HBV lamivudine resistance mutations in a cohort of mono-infected and HIV-co-infected patients

Abstract number: O180

Antonucci G., Solmone M., Piselli P., Vairo F., Vincenti D., Iacomi F., Puro V., Capobianchi M.R.

Objectives: Pattern and prevalence of mutations between HIV-HBV coinfected (HIVpos) and HBV monoinfected (HIVneg) individuals on lamivudine (LAM) therapy have not been extensively documented. We investigated the frequency of mutations and variables potentially associated with an increased risk of HBV mutations in HBsAg+ individuals.

Methods: Among 128 patients tested for LAM resistance, after the exclusion of inappropriate tests (performed <90 days from LAM initiation or >180 days from last LAM treatment) we analysed 102 pts (64 HIVneg and 38 HIVpos). pol gene mutations were assessed by direct sequencing reverse transcriptase fragment 125–213aa, while HBV genotype by comparison with reference sequences. Association of pol mutations with selected factors was assessed by means of odds ratios fitting multiple logistic regression (MLR) equations and their 95% confidence intervals (CI), adjusting for sex, age, HIV- and HCV-coinfection, LAM exposure, HBeAg positivity and HBV genotype.

Results: Average LAM exposure was higher in HIVpos than in HIVneg (39 vs. 29 months, p = 0.054) as well as genotype A prevalence (58% vs. 14%, p < 0.0001). LAM-resistance mutations were detected in 71/102 individuals (69.6%): 26/38 (68%) HIVpos and 45/64 (70%) HIVneg patients. Mutation was significantly associated with prolonged LAM exposure (MLR-OR=4.9 CI:1.2–20.3, >3 vs <1 years) and older age (MLR-OR=1.2 CI:1.0–1.6, for each 5 years increase). M204V mutation was observed in 42 patients (60%); interestingly this mutation was found in almost all HIVpos (24/25, 92%) and only in 18/45 (40%) HIVneg patients (p < 0.0001). Prevalence of triple mutations (M204V+L180M+V173L) was higher in HIVpos (31% vs. 2%, p < 0.001). Independently to HIV-infection, HBeAg expression is more likely to be associated with M204V than M204I mutation (MLR-OR=7.9 CI:1.5–42.8).

Conclusions: In conclusion, main predictor for pol mutations is prolonged LAM exposure. In HIVpos patients, M204V and multiple mutation were more prevalent; independently from HIV positivity, M204V mutation was associated with HBeAg expression. Further studies are needed, to clarify the kinetics and significance of different mutation patterns observed in monoinfected and HIV-HBV-coinfected pts.