Adequate Doses of Ribavirin Are Critical for Achievement of Early Virological Response in HIV-HCV Coinfected Patients

By Liz Highleyman

Overall, HIV/HCV coinfected patients appear to respond less well than HCV-monoinfected individuals to combination therapy for chronic hepatitis C, so adequate doses of pegylated interferon and ribavirin are particularly important for this population.

Given that most pivotal trials of combination therapy in coinfected patients have used an 800 mg/day fixed dose of ribavirin -- rather than 1000-1200 mg/day weight-based dosing -- it is unclear whether HIV infection itself or suboptimal ribavirin exposure explain the observed poorer outcomes in HIV positive patients.

As reported in the June 2007 Journal of Viral Hepatitis, Spanish researchers assessed early virological response in the PRESCO (Peginterferon Ribavirina Espana Coinfeccion) trial.

This multicenter, prospective trial included 389 coinfected individuals with a median age of 40 years; 49% had genotype 1 HCV, 39% had genotype 2 or 3, and 12% had genotype 4. About three-quarters were on HAART, and the median baseline CD4 cell count was 546 cells/mm3. Patients were treated with 180 mcg/week pegylated interferon alpha-2a (Pegasys) plus 1000-1200 mg/day ribavirin (1000 mg if body weight was < 75 kg and 1200 mg if > 75 kg).

The investigators compared the PRESCO results with unpublished data on early HCV kinetics in 2 other large studies:

• The PISG trial, in which HIV negative patients were treated with 1000-1200 mg/day ribavirin;

• The APRICOT trial, in which HIV positive patients received 800 mg/day fixed-dose ribavirin.

A total of 348 coinfected subjects from PRESCO were analyzed, as well as all patients treated with pegylated interferon plus ribavirin who completed 12 weeks of therapy in the 2 comparative studies (435 in PISG and 268 in APRICOT).

Results

• Among genotype 1 patients, rates of rapid virological response (RVR), or undetectable HCV RNA at week 4 (which has the highest positive predictive value for sustained virological response, or SVR), were:

- 33.3% in PRESCO;
- 31.2% in PISG;
- 13% in APRICOT.

• For patients with genotypes 2 or 3, the corresponding RVR rates were:

- 83.7% in PRESCO;
- 84.2% in PISG;
- 37% in APRICOT.

• Among genotype 1 patients, an HCV RNA decline of less than 2 log10 at week 12 (which has the highest negative predictive value for SVR) was observed in

- 25.5% in PRESCO;
- 19.5% in PISG;
- 37% in APRICOT.

• For patients with genotypes 2 or 3, the corresponding rates were:

- 2.1% in PRESCO;
- 2.9% in PISG;
- 12.0% in APRICOT.

Conclusion

The comparative data showed that rapid and early virological response rates were similar in the 2 studies that used higher ribavirin doses, and higher than those observed in the study that used the lower fixed dose.

Based on these results, the authors concluded that, "Prescription of high ribavirin doses enhances the early virological response to HCV therapy in HCV/HIV-coinfected patients, with results approaching those seen in HCV-monoinfected patients."

05/25/07

Reference
B Ramos, M Nunez, A Rendon, and others. Critical role of ribavirin for the achievement of early virological response to HCV therapy in HCV/HIV-coinfected patients. Journal of Viral Hepatitis 14(6): 387-391. June 2007.

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