Hepatitis C Infection Influence on Immune Recovery in HIV-Positive Patients on Successful HAART: The Role of Genotype 3

Elena      Seminari; Carmine      Tinelli; Giovanni      Ravasi; Diego      Ripamonti; Nicoletta      Ladisa; Nicoletta      Marino; Laura      Sighinolfi; Placido      Mondello; Marco      Migliorino; Giampiero      Carosi; Renato      Maserati

Abstract

Objective: The primary objective of this study was to investigate the impact of HCV infection and of HCV genotypes on immune restoration in HIV-infected patients on a successful HAART regimen. Methods: Patients from the MASTER Study were included in this current longitudinal study if they met the following criteria: being on any successful HAART, and availability of CD4+ cell count and HIV RNA level before starting the suppressive HAART and 12 months after suppressive therapy, and availability of HCV antibodies. The primary endpoints of the study were defined as achieving a difference above 100 cell/mmc between CD4+ at baseline and at time of HIV RNA suppression while on therapy (Δ CD4+early), or 12 month after a suppressive therapy (Δ CD4+late). Results: 844 HIV-positive patients were included in the analysis: 673 were HCV-negative and 171 were HCV-positive [92 (53.8%) subjects had HCV genotype 1; 58 (33.9%), genotype 3; 21 (12.3%), genotype 4]. Plasma HIV RNA (both baseline as highest value), nadir CD4+, being naive, time to reach undetectable plasma HIV RNA, treatment with PI vs NNRTI being associated with an early immunological recovery; the occurrence of previous AIDS event, a history of injection drug use, and HCV infection being associated with failure to achieve an early immunological recovery. Variables associated with Δ CD4+late immune recovery were baseline CD4+ value, plasma HIV RNA (both baseline as highest value), being naive and time to reach undetectable plasma HIV RNA. HCV infection per se was not associated with a worse probability to reach late immunologic response, although among HCV infected patients, having a genotype 3 was associated with a worse immune recovery. At multivariable analysis, factors that remained associated with failure to achieve an early immunological response were being HCV infected and history of injection drug use, while those associated with a failure to achieve a late immunological response were infection with HCV genotype 3 and older age. Conclusions: A blunted early immune recovery was observed in HCV infected patients, compared with HCV negative subjects, while late immune recovery was not different among HCV infected as a whole and not infected subjects; only the subgroup of subjects infected with genotype 3 showed an impaired late immune recovery.

Keywords: HIV-HCV coinfection, HCV genotypes, immune recovery on HAART, HIV infection, HIV therapy