- Category: HIV/HCV Coinfection
- Published on Friday, 23 March 2012 00:00
- Written by Liz Highleyman
HIV positive people acutely infected with hepatitis C virus (HCV) genotypes 2 or 3 benefit from receiving weight-based ribavirin in addition to pegylated interferon, according to study findings presented at the 19th Conference on Retroviruses and Opportunistic Infections (CROI 2012) this month in Seattle.
Acute hepatitis C is more easily treated than chronic infection, which has led researchers to explore shorter therapy and use of pegylated interferon alone instead of the pegylated interferon/ribavirin combination used to treat chronic hepatitis C. Simpler therapy may be especially appropriate for people with easier-to-treat HCV genotypes 2 or 3, but this has not been extensively studied in people with HIV, who generally do not respond as well to interferon-based treatment.
Usually hepatitis C is not diagnosed during the acute stage, which is often asymptomatic or has symptoms similar to those of the flu. However, the growing epidemic of sexually transmitted HCV among HIV positive men who have sex with men (MSM) offers more opportunity to treat acute hepatitis C, since this group often receives regular liver function monitoring that can reveal early infection.
Christoph Boesecke from University Hospital Bonn and fellow investigators with the NEAT (European AIDS TreatmentNetwork)study groupevaluate whether adding ribavirin to pegylated interferon would have an effect on sustained virological response (SVR) rates -- or continued undetectable HCV viral load after the end of treatment -- in HIV positive people with various genotypes.
This prospective analysis included 284 HIV positive men diagnosed with acute HCV infection in Austria, France, Germany, and the U.K. The median age was 39 years, 95% were MSM, and 3% were injection drug users. They generally had well-controlled HIV disease; 65% were on antiretroviral therapy and the median CD4 T-cell count was 471 cells/mm3.
A majority of participants (68%) had HCV genotype 1, 5% had genotype 2, 11% had genotype 3, and 17% had genotype 4; three-quarters were asymptomatic. At baseline the median HCV RNA level was about 939,000 IU/mL. About half were tested for IL28B, and 45% had the favorable CC pattern. Overall, HIV-related and HCV-related characteristics were similar between genotype 1/4 and genotype 2/3 patients.
Most participants (n = 254, or 89%) were treated early with pegylated interferon plus ribavirin, but 30 received pegylated interferon alone. Almost everyone treated with combination therapy (88% of all patients) used weight-based doses of ribavirin: 1000 mg if 75 kg or less; 1200 mg if heavier.
The median time from diagnosis to the start of treatment was 9.4 weeks. 59% of genotype 1/4 patients and 74% of genotype 2/3 patients were treated for 24 weeks, the standard duration for acute hepatitis C in HIV negative people regardless of genotype and for HIV negative people with genotype 2/3 chronic hepatitis C. 41% and 26%, respectively, were treated for 48 weeks, the recommended duration for HIV negative people with genotype 1/4 chronic hepatitis C and HIV positive people with chronic hepatitis C regardless of genotype.
- Genotype 1/4 participants first showed undetectable HCV RNA a median of 8 weeks after starting therapy, compared with 5 weeks for genotype 2/3 patients.
- After 12 weeks of therapy, 96% of genotype 2/3 patients treated with pegylated interferon/ribavirin and 67% treated with pegylated interferon monotherapy achieved early virological response (EVR), a statistically significant difference (p = 0.029).
- Sustained virological response rates for genotype 2/3 patients were 94% with pegylated interferon/ribavirin and 60% with monotherapy, which was highly significant (p = 0.007)
- Among people with genotype 1/4, those treated with combination therapy actually had lower EVR (71% vs 86%) and SVR (67% vs 70%) rates than those receiving monotherapy; neither difference was significant, but few in this group received pegylated interferon alone.
- In a multivariate analysis, pegylated interferon/ribavirin combination therapy and rapid virological response at week 4 were significantly associated with SVR in genotype 2/3 patients.
- Among people with genotype 1/4, only rapid virological response was a significant predictor of SVR.
- Frequency and severity of adverse events were similar for people treated with pegylated interferon/ribavirin and pegylated interferon monotherapy.
- Overall, 10% of participants reduced their ribavirin dose and 6% stopped treatment due to side effects.
"Ribavirin is important in the management of acute HCV infection in HIV+ patients," the researchers concluded. "For genotype 2/3 infections, almost all patients clear virus with combination therapy."
"Treatment outcome data from this large cohort also confirm that early antiviral treatment of acute HCV/HIV coinfected individuals results in virological response rates significantly higher than those obtained in treatment of chronic HCV coinfection," they added.
C Boesecke, P Ingiliz, H-J Stellbrink, et al (NEAT Study Group). Ribavirin Is Needed in Addition to Pegylated Interferon for Optimal Treatment Responses in the Treatment of Acute HCV Genotype 2 and 3 Infection in HIV-co-infected Individuals. 19th Conference on Retroviruses and Opportunistic Infections (CROI 2012). Seattle, WA. March 5-8, 2012. Abstract 50.