Hepatic histologic response (HR) to combination therapy among HCV/HIV-coinfected individuals: interferon induces HR independent of sustained virologic response (SVR).

Most HIV/HCV-coinfected patients fail to achieve a sustained virologic response (SVR) to peginterferon-ribavirin therapy. We examined the hepatic histologic response (HR), defined as an improvement in hepatic inflammation scores of two points or more, to combination therapy among HIV/HCV-coinfected subjects. An open label prospective trial treated 32 HIV/HCV-coinfected patients with peginterferon alpha-2b and ribavirin for 48 weeks. Liver biopsies, scored by a single pathologist using the Histology Activity Index (HAI, range 0-18) and Ishak fibrosis scores (range 0-6), were performed before and after treatment. Gene expression profiles of PBMCs were performed using Affymetrix U133A gene chips. A total of 87% of SVR subjects and 88% of nonresponders (NR) had an HR, but no significant change in the liver fibrosis scores was observed (p > 0.05). For genotype 1 patients, a baseline fibrosis score 2 (p = 0.012). Combination therapy for HCV among HIV-coinfected subjects resulted in a modest SVR rate. Persons with mild liver disease had a better SVR rate, suggesting early treatment may be beneficial. Combination therapy resulted in an HR for most of the patients, however, further follow-up of these patients will determine the durability of such an HR.

Predictors for hematopoietic growth factors use in HIV/HCV-coinfected patients treated with peginterferon alfa 2b and ribavirin.

HIV/hepatitis C virus (HCV)-coinfected individuals have accelerated liver disease, increased drug toxicities, and modest responses to peginterferon and ribavirin. Hematologic toxicities necessitating dose reduction or discontinuation are limiting factors to HCV treatment in the coinfected patient. This study aimed to identify predictors for the need of filgrastim and darbepoetin to manage hematologic toxicities so as to maintain patients on full doses of study drugs for the duration of study. The primary study was a single-center, open-label, prospective study to evaluate the safety, efficacy, and viral kinetics of 48-week peginterferon alfa 2b and ribavirin in HIV/HCV-coinfected patients. Complete blood count was monitored at baseline, days 3, 7, 10, 14, and then weekly for the first month, fortnightly until week 8, then monthly from week 12 to 48. Filgrastim was initiated when absolute neutrophil count (ANC) fell below 750 cells/mm(3) and darbepoetin was used when hemoglobin dropped to less than 10 g/dL. All patients experienced decrease in ANC and hemoglobin. Twenty of 30 (66.6%) of patients required hematopoeitic growth factors, 15 (50%) received filgrastim, and 12 (40%) received darbepoetin. Seven (23.3%) required both. Baseline ANC of less than 2250 cells per millimeter and negative rate of change of hemoglobin on day 3 of therapy were excellent predictors for filgrastim and darbepoetin use, respectively. Supplemental growth factors were associated with substantial increase in overall cost for HCV treatment. Larger clinical trials will be needed to address the cost effectiveness of supplemental growth factor use in the HIV/HCV-coinfected patients.