Occult hepatitis B virus infection in the setting of hepatitis C virus (HCV) and human immunodeficiency virus (HIV) co-infection: clinically relevant or a diagnostic problem?

The clinical relevance of occult hepatitis B virus (HBV) infection, defined as detectable HBV DNA serum/liver, in the absence of hepatitis B surface antigen (HBsAg), is unclear. We determined the prevalence of serum occult HBV infection in HIV/HCV co-infected patients enrolled in APRICOT, a randomized multinational trial that investigated the efficacy and safety of peginterferon alfa-2a (40 kDa) plus ribavirin for treatment of HCV. We also examined the effect of prior HBV exposure to liver histology at baseline. Only HBsAg-negative patients were eligible. At screening, serum HBV DNA was assessed by commercial assay (detection limit = 200 copies/mL). Patients were divided into four serological groups: anti-HBs+/anti-HBc+; anti-HBs-/anti-HBc+; anti-HBs+/ anti-HBc-; anti-HBs-/anti-HBc-. Baseline liver biopsy grade and stage were compared among groups. Serum HBV DNA was undetectable in all patients, (n = 866). Results of anti-HBs and anti-HBc was available for 176 patients: 60 (34.1%) anti-HBs+/anti-HBc+; 60 (34.1%) anti-HBs-/anti-HBc+; 11 (6.3%) anti-HBs+/anti-HBc-; 45 (25.6%) anti-HBs-/anti-HBc-. There were no differences among the groups in the histological grade or stage at baseline liver biopsies. Occult HBV infection in serum was not detected in this large immunocompetent cohort. Moreover, prior exposure to HBV did not appear to have any affect on baseline liver histology.

Effect of ribavirin on intracellular and plasma pharmacokinetics of nucleoside reverse transcriptase inhibitors in patients with human immunodeficiency virus-hepatitis C virus coinfection: results of a randomized clinical study.

The intracellular triphosphorylation and plasma pharmacokinetics of lamivudine (3TC), stavudine (d4T), and zidovudine (ZDV) were assessed in a pharmacokinetic substudy, in 56 human immunodeficiency virus-hepatitis C virus (HIV-HCV) coinfected patients receiving peginterferon alfa-2a (40KD) 180 microg/week plus either placebo or ribavirin (RBV) 800 mg/day in the AIDS PEGASYS Ribavirin International Coinfection Trial. There were no significant differences between patients treated with RBV and placebo in plasma pharmacokinetics parameters for the nucleoside reverse transcriptase inhibitors (NRTIs) at steady state (weeks 8 to 12): ratios of least squares mean of area under the plasma concentration-time curve (AUC(0-12 h)) were 1.17 (95% confidence interval, 0.91 to 1.51) for 3TC, 1.44 (95% confidence interval, 0.58 to 3.60) for d4T and 0.85 (95% confidence interval, 0.50 to 1.45) for ZDV, and ratios of least squares mean plasma C(max) were 1.33 (95% confidence interval, 0.99 to 1.78), 1.06 (95% confidence interval, 0.68 to 1.65), and 0.84 (95% confidence interval, 0.46 to 1.53), respectively. Concentrations of NRTI triphosphate (TP) metabolites in relation to those of the triphosphates of endogenous deoxythymidine-triphosphate (dTTP) and deoxcytidine-triphosphate (dCTP) were similar in the RBV and placebo groups. Differences (RBV to placebo) in least squares mean ratios of AUC(0-12 h) at steady state were 0.274 (95% confidence interval, -0.37 to 0.91) for 3TC-TP:dCTP, 0.009 (95% confidence interval, -0.06 to 0.08) for d4T-TP:dTTP, and -0.081 (95% confidence interval, -0.40 to 0.24) for ZDV-TP:dTTP. RBV did not adversely affect HIV-1 replication. In summary, RBV 800 mg/day administered in combination with peginterferon alfa-2a (40KD) does not significantly affect the intracellular phosphorylation or plasma pharmacokinetics of 3TC, d4T, and ZDV in HIV-HCV-coinfected patients.