SUMMARY: Extending treatment with pegyalted interferon plus ribavirin for an extra 3 months raises the odds that HIV/HCV genotype 1 or 4 coinfected people will achieve sustained virological response, or a cure for hepatitis C, according to a Spanish study presented at the recent American Association for the Study of Liver Diseases "Liver Meeting" (AASLD 2010) in Boston. Patients with easier-to-treat HCV genotypes 2 or 3, however, did well with 6 months of treatment if they experienced rapid virological response.

By Liz Highleyman

Past research has shown that HIV positive peoplecoinfected with hepatitis C virus (HCV) tend to experience more rapid liver disease progression and do not respond as well to interferon-based therapy to treat chronic hepatitis C.

For this reason, experts often recommend that HIV/HCV coinfected people should receive treatment for a full year regardless of HCV genotype. In contrast, standard therapy for HIV negative HCV monoinfected individuals is 12 months for hard-to-treat HCV genotypes 1 or 4, but 6 months for genotypes 2 or 3.

Pablo Barreiro from Hospital Carlos III in Madrid and colleagues explored the effect of duration of therapy on treatment response in a study of 185 HIV/HCV coinfected patients. Most (75%) were men, the average age was 43 years, and about 90% had a history of injection drug use.

As a group, participants had well-controlled HIV disease; 85% were on antiretroviral therapy (ART) and the mean CD4 cell count was over 500 cells/mm3. But their liver disease status was less promising: about three-quarters had HCV viral load > 500,000 IU/mL, nearly 70% had HCV genotypes 1 or 4, and more than 40% had advanced (stage F3-F4) liver fibrosis -- all factors associated with poorer treatment response.

Rapid virological response (RVR) to pegyalted interferon plus ribavirin, or undetectable HCV RNA at week 4 of treatment, has been shown to be a good predictor of sustained virological response (SVR), or continued undetectable HCV viral load 24 weeks after completion of therapy, the researchers noted as background. Therefore, length of therapy might be individualized based on early response.

Participants were randomly assigned to receive different durations of treatment with pegyalted interferon alfa-2b (PegIntron) plus weight-adjusted ribavirin -- 6, 12, or 15 months -- and were stratified according to HCV genotype and early response status.

Results

	As expected, participants with HCV genotypes 1 or 4 were significantly more likely to experience RVR (HCV RNA < 10 IU/mL at week 4) than those with genotypes 2 or 3 (16% vs 49%, respectively).
	The overall SVR rate was 36%, but this varied significantly according to genotype, early response, and treatment duration:
	Genotype 2 or 3 with RVR treated for 6 months: 60% Genotype 2 or 3 without RVR treated for 12 months: 77%; Genotype 2 or 3 without RVR treated for 6 months: 17%. Genotype 1 or 4 with RVR treated for 12 months: 65%; Genotype 1 or 4 without RVR treated for 15 months: 62% Genotype 1 or 4 without RVR treated for 12 months: 9%.
	For both genotypes, patients without RVR had significantly higher response rates when treatment duration was extended.
	People who experienced RVR, however, did well with the shorter course of therapy.

"In HIV/HCV coinfected patients, extension of HCV therapy to 15 months improves the chances of SVR in genotype 1/4 carriers without RVR," the investigators concluded. "Likewise, shortening the length of therapy to 6 months may be offered to genotype 2/3 patients with RVR."

Investigator affiliations: Hospital Carlos III, Madrid, Spain; Hospital Reina Sofia, Cordoba, Spain; Hospital Parc Tauli, Barcelona, Spain; Hospital La Princesa, Madrid, Spain; Hospital Central de Asturias, Oviedo, Spain.

11/30/10

Reference
P Barreiro, P Tuma, A Rivero, and others. Length of Peginterferon-Ribavirin Therapy According to HCV Genotype and Rapid Virological Response in HIV/HCV Coinfected Patients: The EXTENT Trial. 61st Annual Meeting of the American Association for the Study of Liver Diseases (AASLD 2010). Boston, October 29-November 2, 2010. Abstract 903.