Background:  In an ongoing 1-part, randomized, double-blind, placebo-controlled, parallel-group, phase 2 trial of telaprevir in combination with pegylated interferon-alfa-2a (peg-IFN-a-2a)+ribavirin (RBV) in genotype 1 HCV treatment-naïve HIV⁺ patients, a week-24 interim analysis was performed.

Methods:  Patients in each part were randomized into 2 groups:  telaprevir 750 mg every 8 hours + pegIFN 180 μg/week + RBV 800 mg/day for 12 weeks followed by 36 weeks of pegIFN+RBV (T/PR group) and placebo + pegIFN+RBV for 48 weeks. The telaprevir dose was 1125 mg every 8 hours when the ART regimen included efavirenz (EFV). In part A, patients had no concurrent ART. In part B, patients were on stable, predefined ART with either an EFV- or an atazanavir (ATV)/ritonavir (r)-based regimen. 

Results:  Of 62 patients randomized, 60 received ≥1 dose, 13 in part A, 47 in part B; 44 patients reached week 24 on the study drug. Mean age was 46 years; 88% were male; 27% were African American; 68% had subtype 1a; 3.3% had cirrhosis. At baseline, 92% and 81% of part A and B patients had HCV RNA ≥800,000 IU/mL, respectively; mean CD4 counts were 690 cells/mm³ and 562 cells/mm³, respectively. Undetectable HCV RNA at week 4, 12, weeks 4 and 12, and week 24 are shown in the table; 2 patients experienced HCV RNA breakthrough on telaprevir (n = 1 EFV, n = 1 ATV/r). There were no HIV RNA breakthroughs. Absolute CD4 counts declined from baseline in both groups, although CD4 percentage remained unchanged. Overall, in the treatment groups compared to placebo, abdominal pain, vomiting, nausea, pyrexia, dizziness, depression, and pruritus occurred ≥10% difference; bilirubin adverse events occurred more frequently in ATV/r patients (27% vs 0%) as did indirect hyperbilirubinemia. No severe rashes were reported. Three treated patients in part B experienced an adverse event (cholelithiasis, jaundice, hemolytic anemia [severe adverse event]) that led to discontinuation of 1 or more study drugs. Telaprevir pharmacokinetics was comparable across ART regimens. The pharmacokinetics of ART when co-administered with telaprevir resulted in changes consistent with prior didanosine (ddI) studies in healthy volunteers.

Conclusions:  At the week-24 interim analysis, substantially higher on-treatment responses were observed in patients treated with a telaprevir-based regimen than placebo. Overall, undetectable HCV RNA at weeks 4 and 12 was achieved in 63% of treated patients compared to 4.5% on placebo. Bilirubinemia was notable in patients treated with an ATV/r-based regimen; however, safety and tolerability of telaprevir in combination with pegIFN+RBV was comparable to that previously observed in HCV-mono-infected patients.