By Liz Highleyman

HIV positive individuals with chronic hepatitis C tend to respond less well to interferon-based therapy than HIV negative people (though recent study results have been mixed). The pivotal APRICOT trial was one of the first to demonstrate that pegylated interferon plus ribavirin is superior to the older conventional interferon or interferon monotherapy in an HIV-HCV coinfected population.

Investigators with the international trial have continued to conduct retrospective analyses of the study data in order to uncover further details about factors associated with treatment success or failure. One such analysis, looking at partial rapid response, was presented at the recent 59th Annual Meeting of the American Association for the Study of Liver Diseases (AASLD 2008).

Briefly, APRICOT included 868 HCV-HIV coinfected patients in 19 countries who were randomly assigned to receive conventional interferon alfa plus fixed-dose 800 mg/day ribavirin, pegylated interferon alfa-2a (Pegasys) plus placebo, or pegylated interferon plus ribavirin for 48 weeks (1,000-1,200 mg/day weight-adjusted ribavirin is now considered the standard of care for this population). The sustained virological response (SVR) rate was highest in the pegylated interferon plus ribavirin arm: 40% overall, 29% for patients with HCV genotype 1, and 62% for those with genotypes 2/3.

In the present analysis, Maribel Rodriguez-Torres and colleagues looked at the 176 coinfected APRICOT participants who had HCV genotype 1 and were randomly assigned to the pegylated interferon plus ribavirin arm. Most (about 80%) were men and the mean age was about 40 years.

Having previously shown that complete rapid virological response (RVR), or undetectable HCV RNA (< 50 copies/mL) at week 4 of therapy, was associated with a high rate of sustained response, the researchers now looked at various degrees of partial rapid response.

Results

• 13% of genotype 1 patients achieved RVR.

• The SVR rate was substantially higher among patients who achieved complete RVR (< 50 copies/mL) at week 4 versus those who did not do so (82% vs 22%, respectively).

• A similar pattern was seen for early virological response (EVR) at week 12 (91% vs 25%, respectively).

• Among patients without complete RVR, the probability of sustained response rose in association with larger 4-week reductions in HCV RNA.

• Among participants with "unquantifiable" HCV RNA (defined as 50-600 copies/mL) at week 4, the SVR rate was 79%.

• Among patients with > 3 log decline at 4 weeks, 43% achieved SVR.

• Among patients with > 2 log decline, 32% achieved SVR.

• Among patients with > 1 log decline, 13% achieved SVR.

• Among patients with less than a 1 log decline at 4 weeks, only 8% achieved SVR.

• A similar pattern was observed with regard to proportions of patients within each partial response subgroup who achieved EVR: 86%, 57%, 36%, 19%, and 6%, respectively).

Based on these findings, the researchers concluded, "Among HIV-HCV coinfected genotype 1 patients treated for 48 weeks with [pegylated interferon alfa-2a plus 800 mg/day ribavirin], at least 3 log reduction in HCV RNA by week 4 or an unquantifiable or undetectable viremia were associated with a high or very high probability of SVR."

Given these results, they recommended that RVR, unquantifiable HCV RNA, or a HCV viral load reduction of > 3 log between baseline and week 4 "should be a strong incentive to continue planned treatment."

"Inclusion of week 4 and week 12 criteria in the treatment algorithm to identify early responders could maximize SVR rates and improve the overall benefit-risk ratio and should be validated in future trials," they added.

11/21/08

Reference
M Rodriguez-Torres, J Rockstroh, J Depamphilis, and others. Prediction of SVR in HCV genotype 1 patients co-infected with HIV based on virological responses at week 4 and 12 of treatment with peginterferon alfa-2a (40KD) (PEGASYS) and ribavirin (COPEGUS): Retrospective analysis of APRICOT. 59th Annual Meeting of the American Association for the Study of Liver Diseases (AASLD 2008). San Francisco. October 31-November 4, 2008. Abstract 1855.