EASL 2010: HIV/HCV Coinfected Patients with Acute Hepatitis C Are Equally Likely to Achieve Sustained Response with Interferon plus Ribavirin

HIV positive people with acute hepatitis C treated with pegylated interferon plus ribavirin, and HIV negative people treated with pegylated interferon alone, had a similar likelihood of achieving rapid virological response (RVR) at week 4 and sustained virological response (SVR) after completing treatment, according to findings presented at the 45th Annual Meeting of the European Association for the Study of the Liver (EASL 2010) last month in Vienna. RVR was the best predictor of SVR, but HIV/HCV coinfected patients had larger HCV viral load reductions between weeks 4 and 12, suggesting that ribavirin promotes "third phase" viral decline.

Gail Matthews and fellow investigators with the Australian Trial in Acute HCV (ATAHC) Study Group prospectively evaluated treatment outcomes among people with acute (first 6 months after infection) and early chronic hepatitis C virus (HCV) infection.

Most studies indicate that people treated during the acute stage of hepatitis C have a high SVR rate, but the likelihood of sustained response has been shown to be lower among injection drug users, HIV/HCV coinfected patients, and people who start therapy later.
Acute hepatitis C is often treated for a shorter duration than chronic infection (e.g., 24 weeks regardless of HCV genotype) and may use pegylated interferon monotherapy without ribavirin. However the optimal regimen for these more challenging groups of patients remains unclear.

The present analysis included more than 100 participants with acute or early chronic HCV infection. Three-quarters had a history of injection drug use and 35% were HIV positive. HIV negative participants were treated with pegylated interferon alfa-2a (Pegasys) for 24 weeks, while those with HIV/HCV coinfection received pegylated interferon plus ribavirin for the same duration.

RNA decline was assessed among adherent participants who took at least > 80% of prescribed doses of pegylated interferon.

Results

• In an oral presentation, the researchers reported that among 89 adherent participants, HIV negative and HIV/HCV coinfected patients had statistically similar average baseline HCV viral load levels (5.04 vs 5.33 log IU/mL) and similar mean declines in HCV RNA through week 4 (2.48 vs 2.94 log).
• 50% of HIV negative participants and 41% of coinfected patients achieved complete RVR (defined as HCV RNA < 10 IU/mL at week 4), again statistically similar.
• However, mean reductions in HCV RNA were significantly greater among the HIV/HCV coinfected patients compared with the HIV negative patients at week 4 (3.91 vs 3.11 log) and week 12 (3.95 vs 3.10 log).
• Among the adherent population, 72% of HIV negative participants and 74% of HIV/HCV coinfected individuals achieved SVR (defined as continued undetectable HCV RNA 24 weeks after completing therapy).
• In a poster presentation, the investigators reported that complete RVR was the best predictor of SVR, with a positive predictive value of 92% in adherent patients regardless of HIV status.
• The positive predictive values of partial RVR (defined as HCV RNA < 630 IU/mL at week 4) and complete early virological response (defined as HCV RNA < 10 IU/mL week 12) were similar for HIV negative and coinfected patients (84% vs 88% for partial RVR; 86% vs 82% for complete EVR).
• The negative predictive value of complete RVR, however, was considerably higher for HIV negative compared with coinfected patients (50% vs 35%).
• The negative predictive values of both partial RVR (63% vs 100%) and complete EVR (82% vs 100%) were "much improved" compared with complete RVR, both reaching 100% for coinfected patients.

"Despite being generally reported to have lower rates of response to therapy than HCV monoinfected patients," the investigators concluded, "adherent HIV/HCV [coinfected] patients in ATAHC achieved RVR at a similar rate to HIV negative participants and experienced greater HCV RNA reductions between week 4 and week 12 of therapy."

These findings, they noted, "would be consistent with an effect of ribavirin on third-phase viral kinetics and suggest a potential benefit for combination therapy in maximizing early virological responses in this setting."

National Centre in HIV Epidemiology and Clinical Research (NCHECR), University of New South Wales, Sydney, NSW; Burnet Institute, Melbourne, Victoria; Virology Division, SEALS Microbiology, Prince of Wales Hospital, Sydney, NSW, Australia.

5/7/10

References

GV Matthews, J Grebely, M Hellard, and others (Australian Trial in Acute HCV Study Group). Differences in early virological decline in individuals treated within the Australian Trial in Acute HCV suggest a potential benefit for the use of ribavirin. 45th Annual Meeting of the European Association for the Study of the Liver (EASL 2010). Vienna, Austria. April 14-18, 2010. (Abstract).

GV Matthews, J Grebely, M. Hellard, and others (Australian Trial in Acute HCV Study Group). Week 4 HCV RNA is the optimal predictor of SVR in both HIV positive and negative subjects within the Australian trial in acute HCV. 45th Annual Meeting of the European Association for the Study of the Liver (EASL 2010). Vienna, Austria. April 14-18, 2010. (Abstract).