Differences in virological response to peginterferon-[alpha] plus ribavirin in HIV-positive patients coinfected with HCV subtypes 1a or 1b

JAIDS Journal of Acquired Immune Deficiency Syndromes:

POST ACCEPTANCE, 22 February 2012

doi: 10.1097/QAI.0b013e31824f5506

Original Article: PDF Only

Rallón, Norma I.; Pineda, Juan A.; Soriano, Vincent; Neukam, Karin; Vispo, Eugenia; Rivero, Antonio; Labarga, Pablo; Caruz, Antonio; Restrepo, Clara; Camacho, Angela; Barreiro, Pablo; Benito, Jose M.

Abstract

Background: Both viral and host factors influence response to peginterferon-[alpha] plus ribavirin (pegIFN[alpha]/RBV) in patients with chronic hepatitis C. The impact of these variables is more pronounced in HIV/HCV-coinfected individuals, in whom treatment response rates are lower.

Methods: Virological responses at multiple time points were assessed in all HIV/HCV-coinfected patients that completed a first course of pegIFN[alpha]/RBV. Viral responses were stratified by HCV geno/subtypes and IL28B rs12979860 variants.

Results: A total of 331 HIV/HCV-coinfected patients were analyzed. HCV geno/subtype distribution was as follows: HCV-1a in 97, HCV-1b in 62, HCV-3 in 122 and HCV-4 in 50. Age, gender, CD4 counts, plasma HIV-RNA and liver fibrosis stage did not differ significantly across HCV geno/subtypes. In contrast, mean serum HCV-RNA was greater in HCV-1a compared to the rest (p<0.0001). The proportion of IL28B CC variants was higher in HCV-3 compared to the rest (p=0.001).

Virological responses were better in HCV-1b than HCV-1a at any given time point during therapy. IL28B variants significantly influenced virological responses across all HCV-1 subtypes, with the strongest effect seen in HCV-1a. In a multivariate linear regression analysis, both HCV-1b and IL28B CC variants were significantly associated with greater HCV-RNA drops at weeks 4 (R=0.52, p<0.0001) and 12 (R=0.49, p<0.0001) of therapy.

Conclusion: The response to pegIFN[alpha]/RBV therapy is lower in HCV-1a than HCV-1b in HIV/HCV-coinfected patients. The strongest influence of IL28B variants is seen in HCV-1a. This information may be relevant when using most directly acting antivirals in coinfected patients along with pegIFN[alpha]/RBV, given that selection of drug resistance occurs more frequently in HCV-1a than HCV-1b.

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