Source aLaboratoire de Virologie, Hôpital Saint-Louis, AP-HP, Paris, France bInserm U941, Paris, France cUniversité Paris-Diderot, Paris, France. dInserm UMR-S707, Paris, France eInserm U1052, Lyon, France fLaboratoire de bactériologie-virologie, Hôpital Saint-Antoine, Paris, France gService de maladies infectieuses, Hôpital Saint-Louis, Paris, France hService de maladies infectieuses, Hôpital de la Croix-Rousse, Hospices Civils, Lyon, France iService de maladies infectieuses, Hôpital Tenon, Paris, France jService de maladies infectieuses, Hôpital Saint-Antoine, Paris, France kUniversité Pierre et Marie Curie, Paris VI, France lService d'hépatologie, Hôpital de la Croix-Rousse, Hospices Civils, Lyon, France mUniversité Lyon 1, Lyon, France.

OBJECTIVE: Hepatitis B surface (HBsAg) and envelope (HBeAg) antigen-loss are the primary goals of treating chronic hepatitis B virus (HBV). Although their quantification is useful for other antivirals, such is not the case with tenofovir disoproxil fumarate (TDF), particularly in HIV-infection.

DESIGN: Prospective, multicenter, cohort study in 143 antiretroviral-experienced HIV-HBV co-infected patients initiating TDF.

METHODS: HBsAg- (IU/ml) and HBeAg-levels (S/CO) were measured every 6 months. HBsAg- and HBeAg-decline (Δ) were assessed by mixed-effect linear models. Quantification criteria were used to assess predictability of antigen-loss with time-dependent receiver operating characteristic curves.

RESULTS: After a median follow-up of 30.3 months, cumulative incidence rate of HBsAg-loss was 4.0% (n = 4) in the entire study population and HBeAg-loss was 21.0% (n = 17) in the 96 HBeAg-positive patients. ΔHBsAg was steady during follow-up (HBeAg-positive: -0.027 and HBeAg-negative: -0.017 log10IU/mL/month), while ΔHBeAg-ratio was strongly biphasic (-27.1 S/CO/month before and -6.5 S/CO/month after 18 months). Baseline HBeAg and ΔHBeAg were significantly different in patients harboring pre-core mutations (p < 0.01), while both ΔHBsAg and ΔHBeAg were significantly slower among HBeAg-positive patients with CD4+ T-cell count <350/mm (p < 0.05). HBeAg-ratio ≤10 S/CO at 12-months of therapy was the optimal marker of HBeAg-loss, with high sensitivity (0.82) and specificity (0.84) at 36-months. In patients with HBsAg-loss, 3/4 (75.0%) had a baseline level of HBsAg ≤400 IU/mL.

CONCLUSIONS: During TDF-treatment, HIV-induced immunosuppression and HBV genetic variability are associated with differences in HBsAg- and HBeAg-decline among antiretroviral-experienced, co-infected patients. Considering the decline of HBsAg-level is slow, further evaluation is needed to determine its role as a marker of therapeutic efficacy.