By Liz Highleyman

Many studies have looked at factors predicting good response to interferon-based therapy in HIV negative chronic hepatitis C patients. While there is some data on predictors of response from clinical trials of HIV-HCV coinfected patients -- such as APRICOT and ACTG A5071 -- less in known about outcomes of routine clinical care in this population. "Real world" outcomes often are not as good as those seen in clinical trials, which include a carefully selected patient population.

As reported at the recent Digestive Disease Week annual meeting (DDW 2009) in Chicago, Lisa Backus and colleagues evaluated the predictors of sustained virological response (SVR) for HIV-HCV coinfected patients receiving pegylated interferon plus ribavirin in routine care at Veterans Affairs (VA) medical facilities.

The researchers identified patients in the VA HIV-HCV coinfection and VA HIV Clinical Case Registry who received a first prescription for pegylated interferon before January 1, 2005, and a ribavirin prescription within 7 days of pegylated interferon. Eligible patients had HCV genotypes 1, 2, or 3 and detectable HCV RNA at baseline.

The analysis included only patients with an HCV RNA measurement available 6 months or more after completion of therapy, indicating sustained response. Individuals who did not have an HCV viral load test after stopping treatment, or who had detectable HCV RNA at any time after treatment, were considered "no SVR."

Results

Among 346 HIV-HCV coinfected patients who started pegylated interferon plus ribavirin, SVR rates were:

9% (26 of 278) for those with genotype 1;
49% (18 of 37) for those with genotype 2;
39% (12 of 31) for those with genotype 3.

Of the baseline factors examined, the following were significant (P < 0.05) predictors of sustained response in a single-factor analysis:

Race/ethnicity;
ALT > 3 times the upper limited of normal;
HCV genotype;
HCV RNA < 500,000 IU/mL;
Type of pegylated interferon alfa (2a [Pegasys] vs 2b [PegIntron]);
Starting on recommended doses of pegylated interferon and ribavirin.
Nadir (lowest-ever) CD4 cell count and concurrent diabetes had a weaker association with SVR (P < 0.1).

In a multivariate analysis, lower HCV RNA, HCV genotype 2 or 3 (vs 1), elevated ALT, and use of pegylated interferon alfa-2a (vs 2b) were significant positive predictors of SVR.

Conversely, diabetes was a significant negative predictor of sustained response.

Most treated VA patients would have been excluded from clinical trials for various reasons.

In this cohort, 57% would have been excluded from APRICOT, for example based on prior use of interferon or lab criteria.

74% might have been excluded based on a current diagnosis of diabetes or depression.

"Our results confirm that HIV-HCV patients with lower baseline HCV RNA and HCV genotype 2 or 3 are more likely to respond to [pegylated interferon]/ribavirin," the researchers concluded. "Baseline ALT, [pegylated interferon] form, and diabetes also substantially impact the likelihood of SVR."

In addition, they noted, "Response rates in routine practice are substantially lower than in clinical trials."

Center for Quality Management in Public Health, Palo Alto HCS, Palo Alto, CA.

6/16/09

Reference
LI Backus, DS Boothroyd, and LA Mole. Predictors of Sustained Virologic Response to Pegylated Interferon and Ribavirin in a National Cohort of Male HIV/HCV-Coinfected Veterans in Routine Medical Care. Digestive Disease Week (DDW 2009). Chicago. May 30-June 4, 2009. Abstract M1785.