Background:  Persons co-infected with hepatitis C virus (HCV)/HIV are reported to have more rapid liver disease progression than those with HCV alone. We hypothesized that maintenance therapy with pegylated interferon could reduce fibrosis progression among non-responders.

Methods:  HCV/HIV-co-infected subjects, naïve/refractory to HCV treatment, were treated with pegylated interferon-α-2a 180 µg/week + weight-based ribavirin 1000 to 1200 mg once daily for 12 to 18 weeks. Early virologic response was defined as HCV RNA undetectable (<600 IU) or 2-log drop at week 12. Non-early virologic responses underwent liver biopsy and were randomized to receive pegylated interferon 180 µg alone or observation for 72 weeks. Liver biopsy obtained at start and end of therapy were blinded and read by a single pathologist; 134 subjects required to determine whether pegylated interferon maintenance produced 0.18 unit/year reduction in the rate of Metavir fibrosis progression.

Results:  We enrolled 330 subjects, of whom 329 initiated pegylated interferon/weight-based ribavirin. Median age was 48 years; 83% male; 43% white, 37% black, non-Hispanic and 15% Hispanic; median HCV viral load was 6.6 log IU; CD4⁺ was 498 cells/mm³; 32% were interferon experienced; 74% had HIV RNA <50 copies/mL at entry. Early virologic response was observed in 55.6% (95%CI 50 to 61%; intent-to-treat analysis) of subjects; 42% achieved undetectable HCV. A strong association identified between early virologic response and gender (male >female), race (white >Hispanic >black), fibrosis (non-cirrhotic >cirrhotic), aspartate aminotransferase (AST) (lower >higher), absolute neutrophil count and hemoglobin (both higher >lower). We randomized 86 non-early virologic responders to pegylated interferon vs observation, of whom 72% were male; 71% non-white; median age was 49 years; median CD4 was 392 cells/mm³; 77% had HIV <50 copies/mL; median HCV RNA was 545,500 IU. Median entry Metavir score was 2; 28% had advanced fibrosis (F3, F4). A Safety Monitoring Committee determined that the maintenance hypotheses could not be tested due to the lack of progression with observation. Prior to early closure, 62 entries completed 72 weeks. Of the 62, 45 have paired liver biopsy (24 pegylated interferon, 21 observation). median fibrosis change was 0.0 units/year (Q1,Q3: –0.69, 0.61) with observation compared to the expected rate of 0.18 units/year. Pegylated interferon-treated subjects also had a median fibrosis score change of 0.0 (Q1,Q3: 0.0, 0.69)

Conclusions:  Pegylated interferon/weight-based ribavirin achieved higher levels of early virologic response than observed in ACTG 5071 which used lower doses of ribavirin (55.6% vs. 41%). Race appears to be an important independent factor in early virologic response. In contrast to recent reports, this randomized controlled trial failed to identify significant change in hepatic fibrosis among untreated non-early virologic responses over 72 weeks.