HIV positive individuals who receive treatment soon after becoming infected with hepatitis C virus (HCV) have a high likelihood of sustained response, according to a study presented on Thursday at the Forty-Sixth Interscience Conference on Antimicrobial Agents and Chemotherapy in San Francisco.
In recent years, researchers from the United Kingdom, Germany, and the Netherlands have reported outbreaks of apparently sexually transmitted HCV among HIV positive men who have sex with men. In various analyses, HCV infection has been linked to anal fisting, unprotected receptive anal intercourse, intranasal use of recreational drugs, other sexually transmitted infections, and meeting sexual partners at sex clubs or over the Internet. (see report from 2006 conference on recent risk factors)
Past studies of HIV negative individuals with acute hepatitis C have shown excellent rates of response to interferon-based therapy (as high as 98%). After a retrospective analysis of 11 HIV-positive men with acute HCV found that 91% achieved sustained virological response (SVR), researchers with the German Hepatitis Group decided to conduct a prospective trial in this population.
The study enrolled 70 participants with acute HCV infection, defined as meeting at least two of the following conditions: known or suspected recent exposure to HCV; documented anti-HCV antibody seroconversion; and/or alanine aminotransferase (ALT) levels above 350 IU/L following normal levels during the prior year. All participants had detectable HCV RNA.
Participants were offered treatment with pegylated interferon (180 mcg/week Pegasys or 1.5 mcg/kg/week Peg-Intron) for 24 weeks; a small number received therapy for 48 weeks. Partway through the study, weight-based ribavirin was added for patients with HCV genotypes 1 or 4, since research has shown that ribavirin reduces the risk of relapse. In another amendment, a “watch and wait” strategy was adopted for participants with hepatitis symptoms during the first 12 weeks, as such people are more likely to spontaneously clear HCV without treatment.
SVR data were available for 47 patients, of whom 36 started therapy and 11 remained untreated (nine declined treatment and two were in the “watch and wait” phase). In total 12 patients went through a `watch and wait' phase.
All participants were men, with an average age of 38 years. Thirty-two individuals had HCV genotype 1, two had genotype 2, six had genotype 3, five had genotype 4, and two had other unspecified genotypes.
Baseline characteristics varied somewhat between the treated and untreated groups. Treated patients had a median HCV RNA level of about 1,900,000 IU/mL, compared with about 750,000 IU/mL for the untreated group. The median ALT was about 250 IU/L. Among the untreated individuals, 73% experienced hepatitis symptoms and 27% developed jaundice; these rates were considerably lower (47% and 8%, respectively) for treated patients, although this difference was not reported to be statistically significant.
With regard to HIV status, participants overall had well-controlled disease. Median CD4 cell counts were 416 cells/mm3 in the treated group and 587 cells/mm3 in the untreated group. Median HIV viral loads were about 55,500 for treated patients and about 62,500 for untreated participants. Roughly half in each group were on HAART.
Among the 11 untreated participants, only three (27%) experienced spontaneous HCV clearance – considerably lower than rates seen in previous studies of HIV negative individuals. Seven participants had undetectable HCV RNA during the first 12 weeks of follow-up, but four of these nevertheless went on to develop chronic HCV infection. The likelihood of spontaneous clearance was not predicted by HCV genotype, HCV or HIV viral load, CD4 count, use of HAART, ALT level, or hepatitis symptoms.
Among the 36 treated patients, in an intent-to-treat analysis, 72% had undetectable HCV viral load at the end of treatment. After 24 additional weeks of follow-up, 61% achieved SVR. As with spontaneous clearance, treatment response rates did not differ significantly based on HCV or HIV viral load, CD4 count, HAART, or ALT level. Unexpectedly, patients who added ribavirin were somewhat less likely to achieve sustained response than those treated with pegylated interferon alone.
Treated patients experienced typical interferon-related side effects -- including depression and decreased blood cell counts -- but there were mostly mild to moderate. Eight individuals experienced Grade 3-4 ALT elevations during treatment.
Based on these results, the researchers concluded that immediate therapy with pegylated interferon leads to sustained virological response in nearly two-thirds of HIV-infected patients.
“We all expect HIV-positive patients will do a little less well than HIV negative individuals,” said lead investigator Martin Vogel, “but in light of that, in this study they did quite well.”
Vogel suggested that a combined analysis of data from all the HIV positive patients with acute sexually transmitted hepatitis C in the various European cohorts might provide additional valuable information.