SUMMARY: About 65% of coinfected patients with HCV genotypes 1 or 4, and 81% with genotypes 2 or 3, achieved sustained response to interferon-based therapy started during acute infection, researchers reported at CROI 2011.

By Liz Highleyman

An estimated one-third of people with HIV are also infected with hepatitis C virus (HCV), which is now regarded as a sexually transmitted infection among HIV positive gay and bisexual men.

Coinfected individuals tend to experience more rapid liver disease progression than those with HCV alone, and they do not respond as well to interferon-based treatment for chronic hepatitis C. But starting hepatitis C therapy early, during acute infection, can lead to better outcomes. Acute HCV infection is often asymptomatic, but HIV positive men have a better chance of detecting HCV early because they undergo regular liver function monitoring that can reveal HCV-related abnormalities.

As reported at the 18th Conference on Retroviruses and Opportunistic Infections (CROI 2011) this month in Boston, Christoph Boesecke and fellow investigators with the European NEAT Study compared hepatitis C treatment outcomes among coinfected patients with different HCV genotypes.

This prospective analysis included 238 HIV positive participants from Austria, France, Germany, and the U.K. who were diagnosed with acute HCV infection. All were men and the median age was 39 years. Most were presumably infected via sex with men; only 3% reported a history of injection drug use. A majority had hard-to-treat HCV genotypes 1 (66%) or 4 (16%), while 6% had genotype 2 and 12% had genotype 3; nearly half had high baseline HCV viral load. Participants had generally well-controlled HIV; about two-thirds were on antiretroviral therapy and the median CD4 cell count was about 470 cells/mm3. About 20% also had other sexually transmitted diseases.

All participants in this non-randomized study started hepatitis C treatment early using pegylated interferon alone (n = 31) or in combination with ribavirin (n = 207), usually dosed according to weight. Treatment began a median of 10 weeks after presumed date of HCV infection. Most men (70%) received treatment for 24 weeks while 30% were treated for 48 weeks; duration did not differ significantly according to HCV genotype. (Standard therapy for chronic hepatitis C for monoinfected patients is 24 weeks for genotypes 2 or 3 and 48 weeks for genotypes 2 or 3.)

Results

	About 75% of participants had no clinical signs of acute HCV infection.
	After 4 weeks of treatment, 51% of genotype 1 or 4 patients and 65% of genotype 2 or 3 patients experienced rapid virological response (RVR), or undetectable HCV RNA viral load -- not a statistically significant difference.
	At 12 weeks, 73% of genotype 1 or 4 patients and 90% of genotype 2 or 3 patients achieved early virological response (EVR), which was a significant difference.
	76% and 95%, respectively, had undetectable HCV RNA at the end of treatment (ETR), again significant.
	24 weeks after completion of therapy, 65% and 81% respectively, achieved sustained virological response (SVR), also significant.
	HCV RNA first became undetectable after a median of 8 weeks.
	18% of patients stopped treatment early, 10% lowered their dose of ribavirin, and 6% reduced their dose of interferon due to side effects, with no significant differences according to HCV genotype.
	In a multivariate analysis, significant factors associated with SVR were:
	Having HCV genotypes 2 or 3; Achieving RVR at week 4.
	However, CD4 count, baseline HIV or HCV viral load, and use of combination therapy vs pegylated interferon monotherapy were not significant predictors of sustained response.

Based on these findings, the researchers concluded, "Early antiviral treatment of acute HCV infection in HIV co-infected individuals results in [sustained virological response] rates which are far higher regardless of HCV genotype than SVR rates in treatment of chronic HCV coinfection."

Despite similar rates of RVR, they continued, "treatment of acute HCV genotype 2 and 3 infection is associated with a higher SVR rate than genotype 1 and 4 infection."

Interestingly, the sustained response rates in this study of HIV/HCV coinfected patients compared favorably to the average 60%-80% response rates seen in most studies of HCV monoinfected individuals with acute infection. In the case of chronic infection, most studies have found that coinfected patients do not respond as well as those with HCV alone.

Investigator affiliations: Univ Hosp Bonn, Germany; ICH Hamburg, Germany; Ctr for HIV and Hepatogastroenterology, Düsseldorf, Germany; Chelsea and Westminster Hosp, London, UK; Royal Free Hosp, London, UK; INSERM U943 and UMR S943, Univ Pierre and Marie Curie, Paris, France; Hosp Pitie-Salpetriere, Paris, France.

3/29/11

Reference
C Boesecke, H-J Stellbrink, S Mauss, et al (NEAT Study Group). Does Baseline HCV Genotype Have an Impact upon Treatment Outcome of Acute HCV Infection in HIV Co-infected Individuals? 18th Conference on Retroviruses and Opportunistic Infections (CROI 2011). Boston. February 27-March 2, 2011. Abstract 113.