Coinfection

End-of-Treatment Response to Interferon-based Therapy Reduces Liver Failure and Death in HIV/HCV Coinfected Patients

HIV/HCV coinfected individuals who experience an end-of-treatment response to interferon-based therapy for chronic hepatitis C virus (HCV) infection had a greatly reduced risk of liver decompensation and liver-related death, even if they did not go on to achieve sustained virological response, according to a Spanish study presented at the 50th Interscience Conference on Antimicrobial Agents and Chemotherapy (ICAAC 2010) last week in Boston.

Juan Berenguer and fellow investigators with the GESIDA 3603 Cohort Study Group looked at the impact of end-of-treatment response (ETR), or undetectable HCV viral load at the completion of therapy, on liver-related outcomes among study participants who did not go on to achieve sustained virological response (SVR), or continued undetectable HCV RNA at 24 weeks after the end of treatment (considered a cure).

Previous research has shown that sustained response to pegylated interferon plus ribavirin reduces liver-related complications such as decompensation (liver failure) and liver-related death among coinfected patients, the researchers noted as background, but the effects of end-of-treatment response without SVR are not well known.

The present analysis looked at 1428 HIV/HCV coinfected participants in the GESIDA 3603 Cohort who were treated with pegylated interferon/ribavirin at 9 centers in Spain. Observation started at the conclusion of treatment and continued until death or the last follow-up visit. The median follow-up period was about 4 years.

Results

• Among the total 1428 study participants:
• 697 (48.9%) were non-responders (median 49 months of follow-up);
• 211 (14.8%) achieved end-of-treatment response but not sustained response (median 47 months of follow-up);
• 520 (36.4%) were sustained responders (median 47 months of follow-up).
• Patients with ETR and those with SVR had a similar risk of liver-related death, which was significantly lower than that of non-responders:
• ETR patients: 1 death (0.5%);
• SVR patients: 2 deaths (0.4%);
• Non-responders: 35 deaths (5.0%).
• Patients in the ETR group had a significantly higher rate of liver decompensation than sustained responders, but this was again significantly lower than the non-responder rate:
• ETR patients: 9 cases (4.3%);
• SVR patients: 2 cases (0.4%);
• Non-responders: 35 cases (11.0%).
• In a multivariate analysis, both ETR and SVR were significantly associated with reduced risk of liver-related events (decompensation, liver cancer, liver transplant, or liver-related death), after adjusting for age, sex, risk group, HIV disease stage, lowest-ever CD4 cell count, HCV genotype and viral load, and fibrosis stage:
• ETR: adjusted hazard ratio of 0.4 relative to non-response;
• SVR: adjusted hazard ratio of 0.8 relative to non-response.

Based on these findings, the investigators concluded, the best outcomes were achieved among patients who achieved SVR, but ETR was associated with less liver-related mortality and decompensation than non-response.

Hosp Gregorio Maranon, Madrid, Spain; Hosp La Paz, Madrid, Spain; Hosp Vall d'Hebron, Barcelona, Spain; Hosp Clínico de San Carlos, Madrid, Spain; Hosp. Univ. Rio de Guadalajara, Guadalajara, Spain; Hosp Severo Ochoa, Madrid, Spain; Hosp. de Getafe, Getafe, Spain; Fundación SEIMC GESIDA, Madrid, Spain.

9/21/10

Reference

J Berenguer, J Alvarez Pellicer, P Miralles, and others (Gesida 3603 Cohort Study Group). Clinical Consequences of Achieving End of Treatment Response (ETR) but not Sustained Virologic Response (SVR) to Interferon Plus Ribavirin (IF-RB) in HIV/HCV-Coinfected Patients. 50th Interscience Conference on Antimicrobial Agents and Chemotherapy (ICAAC 2010). Boston, September 12-15, 2010. (Abstract V-1784).