Tenofovir-based combination therapy for HIV/HBV co-infection: factors associated with a partial HBV virological response in patients with undetectable HIV viraemia.

OBJECTIVE: The aim of this study was to identify and describe patients with detectable hepatitis B virus (HBV) DNA in the presence of undetectable HIV RNA after 48 weeks of tenofovir disoproxil fumarate (TDF)/emtricitabine (FTC) or lamivudine (3TC) treatment.
DESIGN: Case-control study. Cases or delayed responders were defined as detectable HBV DNA (>20 IU/ml) with undetectable HIV RNA (<40 c/ml) after 48 weeks TDF/3(F)TC combination therapy. Controls or virological responders were defined as both undetectable HIV and HBV after 48 weeks TDF/3(F)TC therapy.
RESULTS: Twenty-three cases were identified and matched to 24 controls. 87% cases and 46% controls were eAg-positive (P=0.005). Nine of 23 (39%) cases and seven of 24 (29%) controls had 3TC monotherapy prior to TDF. Similar proportions had 3TC/FTC resistance pre-TDF (30% cases, 24% controls). The cases had significantly higher baseline HBV DNA pre-3TC (median 1.2×10(8) vs. 3.1×10(6) IU/ml; P=0.009) and pre-TDF (1.1×10(8) vs. 2.6×10(4) IU/ml; P=0.012). Sixteen of 23 cases eventually achieved undetectable HBV DNA after 42.2 (27.2, 54.9) months. Six of 23 still have detectable HBV DNA after 46.2 (28.2, 65.6) months. Only one delayed responder patient developed a new 3(F)TC mutation and they received intensification with entecavir and achieved undetectable HBV DNA. No patient developed TDF resistance.
CONCLUSION: We report the largest series of HIV/HBV co-infected patients failing to achieve undetectable HBV after 48 weeks TDF/3(F)TC despite undetectable HIV viraemia. This outcome was associated with positive eAg and higher baseline HBV DNA. Our data suggest that clinicians should not intensify therapy with entecavir unless there is evidence of new 3TC/FTC mutations as the majority of patients go on to suppress HBV. TDF resistance was not seen.