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Undetectable HCV Viral Load at Week 4 of Pegylated Interferon plus Ribavirin Predicts Sustained Response in HIV-HCV Coinfected Patients

By Liz Highleyman

Data continue to accumulate indicating that early virological response to interferon-based therapy predicts long-term treatment outcome, according to the latest report from the Spanish PRESCO study, published in the January 2, 2008 issue of AIDS.

PRESCO is a prospective, open-label, multicenter trial evaluating the safety and efficacy of 180 mcg/week pegylated interferon alpha-2a (Pegasys) plus 1000-1200 mg/day weight-based ribavirin. The study included 389 HIV-HCV coinfected participants: 49% with genotype 1, fewer than 1% with genotype 2, 38% with genotype 3, and 12% with genotype 4. Most (74%) were on HAART and the mean CD4 cell count was 546 cells/mm3.

Patients with HCV genotypes 1 or 4 were treated for either the standard duration of 48 weeks or an extended duration of 72 weeks; those with genotypes 2 or 3 were treated for either the standard 24 weeks or an extended 48 weeks. Participants discontinued therapy if they did not achieve at least a 2-log decrease in HCV viral load by Week 12.

For each genotype, baseline HCV RNA and rapid virological response (RVR), defined as HCV RNA below 50 IU/mL at week 4, were evaluated as predictors of sustained virological response (SVR) in an on-treatment analysis.

Results

• Overall, 193 patients (49.6%) achieved SVR:

- 68 of 191 (35.6%) with genotype 1;
- 110 of 152 (72.4%) with genotypes 2 or 3;
- 15 of 46 (32.6%) with genotype 4.

• RVR was the best predictor of SVR regardless of genotype.

• Baseline HCV RNA below 500,000 IU/mL was also associated with SVR only among genotype 1 patients.

• Among genotype 3 patients, RVR had a positive predictive value (PPV) for SVR of 90% with treatment for 24 or 48 weeks.

• Among genotype 1 patients with RVR, the PPV for SVR was 69%.

• Among genotype 4 patients with RVR, the PPV was 83%.


Conclusion

"Undetectable HCV RNA at week 4 is the best predictor of curing chronic hepatitis C in HCV-HIV coinfected patients," the authors concluded. "In HCV [genotype] 1 patients, baseline HCV-RNA also predicts response."

They added that for HIV patients with HCV genotype 3, "RVR may permit shortening therapy duration to only 24 weeks of [pegylated interferon] plus 1000-1200 mg ribavirin."

The ability to reliably determine early in the course of treatment which patients are likely to achieve sustained response allows the rest to forgo the side effects and cost of further futile therapy.

01/08/08

Reference
L Martin-Carbonero, M Nunez, A Marino, and others. Undetectable hepatitis C virus RNA at week 4 as predictor of sustained virological response in HIV patients with chronic hepatitis C. AIDS 22(1): 15-21, January 2, 2008.