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Sustained Response to Pegylated Interferon plus Ribavirin in HIV/HCV Coinfected Patients with Advanced Immune Suppression

SUMMARY: HIV/HCV coinfected individuals with advanced immune suppression are about as likely to achieved sustained virological response to interferon-based treatment as coinfected patients with better preserved immune function, but response rates are lower than those for HIV negative chronic hepatitis C patients, according to a report in the October 15, 2009 issue of Clinical Infectious Diseases.

By Liz Highleyman

Numerous studies have shown that HIV positive people tend to experience more rapid liver disease progression and respond less well to interferon-based therapy than HIV negative people with chronic hepatitis C virus (HCV) infection.

Some evidence indicates that HIV/HCV coinfected patients with well-preserved immune function -- indicated by a high CD4 T-cell count -- may fare nearly as well as those with HCV monoinfection, but outcomes for people with advanced immune suppression are not well understood.

Spanish researchers therefore conducted a study to assess the safety and efficacy of hepatitis C treatment in a clinical cohort of HIV/HCV coinfected individuals with severe immunodeficiency. The analysis included 542 participants treated with pegylated interferon plus ribavirin between June 2001 and April 2007.

Outcomes of interest were sustained virological response (SVR), or continued undetectable HCV RNA 24 weeks after completion of therapy, and emergence of AIDS-defining events while undergoing hepatitis C therapy. SVR rates were compared between patients with advanced immune suppression, defined as a CD4 count <250 cells/mm3 at baseline, and those with higher CD4 cell levels.


Patients with <250 cells/mm3 were somewhat less likely to achieve SVR than those with higher counts (26% vs 39%, respectively), but the difference did not reach statistical significance (P = 0.09).
In a nested case-control study of matched patients, the corresponding sustained response rates were 26% vs 32%, respectively, and the difference was further from statistical significance (P = 0.5).
In a multivariate analysis, baseline CD4 cell count was not a significant predictor of sustained treatment response.
Only 2 participants (5%) with a CD4 count <250 cells/mm3 developed AIDS-related opportunistic illnesses during follow-up.
Patients with CD4 counts <250 cells/mm3 had a trend toward greater likelihood of severe hematological (blood cell) toxicities (41% vs 29%, respectively) and interferon or ribavirin dose reductions (31% vs 20%, respectively), but again these differences were not significant (both P = 0.1).

Based on these findings, the investigators concluded, "The efficacy of pegylated interferon plus ribavirin in HIV/HCV coinfected patients with advanced immunosuppression is substantial and not significantly different to that observed in the overall coinfected population. HCV therapy is generally safe in the population of coinfected patients with advanced immunosuppression."

The sustained response rates observed in this study were considerably lower than those obtained in most studies of HCV monoinfected patients, typically around 50% overall (all genotypes together). However, some studies of coinfected patients with well preserved immune function -- such as the Spanish PRESCO trial -- have produced SVR rates approaching those of HIV negative individuals.

Unidad de Enfermedades Infecciosas, Servicio de Medicina Interna, Hospital Universitario de Valme, Hospital Universitario Virgen del Rocío, Sevilla, Spain.


JA Mira, A Gutierrez-Valencia, ID Gil, and others. Efficacy and Safety of Pegylated Interferon plus Ribavirin in HIV and Hepatitis C Virus-Coinfected Patients with Advanced Immunosuppression. Clinical Infectious Diseases 49(8):e84-91. October 15, 2009.


























HIV-HCV Confection
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International Guidelines for Management of HIV-HCV Coinfection

FDA-approved Combination Therapies for Chronic HCV Infection
Pegasys + Copegus
PEG-Intron + Rebetol
Intron A + Rebetol
Roferon A + Ribavirin

Treatment Guidelines
FDA-approved Combination Therapies for HIV and AIDS Infection
Protease Inhibitors PIs
non Nucleoside Reverse
Transcriptase Inhibitors nNRTIs
Nucleoside / Nucleotide Reverse
Transcriptase Inhibitors NRTIs

Fixed-dose Combinations

Entry / Fusion Inhibitors EIs
Integrase Inhibitors