Anti-hepatitis B virus (HBV) nucleos(t)ides analogs (NA) exert selective pressures on polymerase (pol) and surface (S) genes, inducing treatment resistance and increasing the risk of
vaccine escape mutants. The rate of emergence for these mutations is largely unknown in patients coinfected with human immunodeficiency virus (HIV) and HBV undergoing dual-active
therapy. In a 3-year, repeat-sampling, prospective cohort study, HBV viral genome sequences of 171 HIV-HBV coinfected patients, presenting with HBV
viremia for at least one visit, were analyzed every 12 months via
DNA chip. Logistic and Cox proportional hazard models were used to determine risk factors specifically for S gene mutations at baseline and during follow-up, respectively. HBV-
DNA levels >190 IU/mL substantially decreased from 91.8% at inclusion to 40.3% at month 36 (P < 0.001), while
lamivudine (
LAM) or
emtricitabine (
FTC) use remained steady (71.9%) and
tenofovir (TDF) use expanded (month 0, 17.5%; month 36, 66.7%; P < 0.001). The largest increase of any mutation class was observed in l-
nucleoside-associated pol gene/
antiviral-associated S gene mutations (cumulative incidence at the end of follow-up, 17.5%) followed by alkyl
phosphonate-associated pol-gene (7.4%), immune-associated S gene (specifically any
amino acid change at positions s120/s145, 6.4%), and d-
cyclopentane-associated pol-gene mutations (2.4%). Incidence of l-
nucleoside-associated pol-gene/
antiviral-associated S gene mutations was significantly associated with concomitant
LAM therapy (adjusted hazard ratio [HR], 4.61; 95% confidence interval [CI], 1.36-15.56), but inversely associated with TDF use (adjusted HR/month, 0.94; 95% CI,0.89-0.98). Cumulative duration of TDF was significantly associated with a reduction in the occurrence of immune-associated S gene mutations (HR/month, 0.88; 95% CI, 0.79-0.98). No major liver-related complications (e.g.,
fulminant hepatitis, decompensated liver, and
hepatocellular carcinoma) were observed in patients with incident mutations.
CONCLUSION: