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While achievement of sustained virological response (SVR) to interferon-based therapy is associated with a lower risk of long-term liver-related complications and death among HIV-HCV coinfected patients,well under half of coinfected people are sustained responders to current standard treatment, and the rate is even lower among patients with HCV genotypes 1 or 4, pre-existing severe liver fibrosis or cirrhosis, or black race/ethnicity. The appropriate course of management for coinfected patients who have not achieved SVR after a course of treatment is an open question. One strategy that has been tried in hepatitis C monoinfected individuals -- and now in HIV-HCV coinfected patients -- is maintenance monotherapy using pegylated interferon. At the 15th Conference on Retroviruses and Opportunistic Infections last week in Boston, researchers resented results from the SLAM-C study (ACTG 5178), in which 329 HIV-HCV coinfected patients were first treated with standard of care therapy consisting of 180 mcg once-weekly pegylated interferon alfa-2a (Pegasys) plus 1,000-1,200 mg/day weight-based ribavirin. Most participants (83%) were male, with a median age of 48 years. By race/ethnicity, 43% were white, 37% were black, and 15% were Hispanic. Most (84%) had HCV genotype 1; all had at least mild fibrosis (Metavir stage F1) and 13% had cirrhosis (F4). About one-third had received previous interferon-based therapy. Most had well-controlled HIV disease, with a median CD4 cell count of 498 cells/mm3 and about 75% with HIV viral load below 50 copies/mL. Treatment
response was assessed at 12 weeks. Those who did not achieve early virological
response (EVR, at least a 2 log drop in HCV RNA) at this point were randomly assigned
to receive maintenance monotherapy with the same dose of pegylated interferon
for 72 weeks or to undergo observation without further treatment. Some 12 week
responders who later relapsed were allowed to roll back into the maintenance therapy
arm, and some additional non-responders who had received similar treatment outside
the trial joined at the start of the maintenance phase. Liver biopsies obtained
before and after treatment were compared for evidence of fibrosis.
Conclusion Based on these findings, the researchers concluded that this randomized controlled trial "failed to identify significant change" in liver fibrosis in patients treated with pegylated interferon monotherapy for 72 weeks. The study was not able to demonstrate that interferon maintenance reduced fibrosis progression largely due to the unexpectedly low rate of progression in the observation group. These results conflict with some prior non-randomized observational studies that have shown both rapid fibrosis progression among HIV-HCV coinfected people and slower progression in HCV monoinfected individuals receiving interferon maintenance therapy. However, as recently reported, the randomized HALT-C trial of long-term, low-dose Pegasys maintenance monotherapy in HIV negative individuals failed to demonstrate reduced fibrosis progression. Further controlled studies will be needed to resolve these discrepancies and to determine the best way to manage both HIV positive and HIV negative people with chronic hepatitis C who do not achieve sustained response with currently available therapies. Univ
of Cincinnati, OH; Harvard Sch of Publ Hlth, Boston, MA; Univ of Pittsburgh, PA;
Armed Forces Inst of Pathology, Washington, DC; Beth Israel Deaconess Med Ctr,
Boston, MA; NIAID, NIH, Bethesda, MD; Univ of California, San Francisco, CA; Johns
Hopkins Univ, Baltimore, MD; Massachusetts Gen Hosp, Boston, MA. Reference
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Long-term
Pegylated Interferon Maintenance Therapy Demonstrates No Benefit in HIV-HCV Coinfected
Patients 
Results
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