Boosted Fosamprenavir (Lexiva) Linked to Increased Anti-HCV Immune Response and Lower HCV Viral Load in HIV-HCV Coinfected Patients

Many experts recommend that combination antiviral therapy for chronic hepatitis C using pegylated interferon plus ribavirin should be started after HAART has produced significant immune recovery, since coinfected patients with higher CD4 cell counts tend to respond better to anti-HCV therapy and experience fewer side effects. On the other hand, treating hepatitis C first may improve liver health and make it easier for some patients to tolerate antiretroviral therapy.

But some new data presented at the recent 58th Annual Meeting of the American Association for the Study of Liver Diseases in Boston suggests that the specific drugs in a HAART regimen may influence immune response to HCV.

Italian researchers aimed to evaluate the effect of the protease inhibitor fosamprenavir (Lexiva) on immune function in 10 antiretroviral-naive HIV-HCV coinfected patients before starting treatment with interferon plus ribavirin. Subjects had been infected with HCV for at least 1 year. HAART included AZT (Retrovir) + 3TC (Epivir) + ritonavir-boosted fosamprenavir, all twice daily. Patients did not receive treatment for hepatitis C during the study period.

Results

·         At the start of HAART, the mean CD4 count was 186 cells/mm³, mean ALT and AST were 121 and 93 IU/L, mean HCV RNA was 569 x 10³ IU/mL, and mean HIV RNA was 90 x 10³ IU/mL.

·         Elispot assays identifying specific responses revealed interferon-gamma 62 ± 10 and IL-4 93 ± 12 spot-forming colonies.

·         After 1 month, mean CD4 count had risen to 414 cells/mm³ and HIV RNA had fallen to 209 IU/mL.

·         More surprisingly, ALT and AST had dropped to 22 and 25 IU/L, respectively.

·         HCV RNA fell to 13 x 10³ IU/mL, and 2 patients (20%) achieved undetectable HCV viral load.

·         Elispot responses were interferon gamma 112 ± 14 and IL-4 52 ±16 spot-forming colonies, indicating increased activity.

·         After 3 months, the mean CD4 count was 486 cells/mm³ and patients overall had undetectable HIV and HCV viral load and normal ALT and AST levels.

Conclusion

Based on these findings, the researchers concluded, “Fosamprenavir treatment in HAART schedule induces a decrease of HIV RNA with CD4+ increasing within the first month, but more interestingly also a rapid HCV virological and biochemical response with a boost of Th1 immune network.”

They suggested that, “Fosamprenavir treatment may be an important strategy” in the treatment of antiretroviral-naive HIV-HCV coinfected patients who are not receiving anti-HCV therapy.

11/16/07

Reference
A Perrella, S Grattacaso, M Gnarini, and others. Fosamprenavir in HAART schedule induces a rapid virological and biochemical response to HCV coupled to Th1 boosting in HIV/HCV coinfected patients. 58th Annual Meeting of the American Association for the Study of Liver Diseases. Boston. November 2-6, 2007. Abstract 264.