The Dose-Response Relationship of Peginterferon Alfa-2a and Ribavirin in the Treatment of Patients Coinfected with HIV-HCV

Purpose: The relationship between peginterferon/ribavirin exposure and the probability of achieving a sustained virologic response (SVR) in HIV-HCV coinfected patients is not well described. We conducted a retrospective analysis of HIV-HCV coinfected patients randomized to 48 weeks of treatment with peginterferon alfa-2a (40 kD) 180 mu g/week and ribavirin 800 mg/day in the multinational APRICOT study to define optimal exposure thresholds. Method: Actual drug exposure was estimated in 287 patients, taking into consideration dose reductions for adverse events or laboratory abnormalities. Results: SVR overall and SVR in those completing treatment was, respectively, 29% and 37% among HCV genotype-1 patients and 59% and 68% among genotype non-1 patients. No patients with <= 40% exposure to ribavirin achieved an SVR. Receiver operating characteristic analysis identified that threshold exposures to both drugs of >75% (genotype-1) and >60% (genotype non-1) are associated with SVR. An existing generalized additive model populated with data from HCV monoinfected patients was updated to predict an overall SVR of 37% if genotype-1 patients received ribavirin 1000 or 1200 mg/day but at the cost of a higher incidence of anemia (23%). Conclusion: Completion of scheduled treatment and exceeding certain thresholds for exposure to peginterferon alfa 2a (40 kD) and ribavirin is associated with higher SVR rates.