title: Hepatitis C infection on immune recovery in HIV-positive patients on successful HAART: the role of genotype 3.
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, availability of CD4+ cell count and HIV RNA level before starting the suppressive HAART and 12 months after suppressive therapy, 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 (DeltaCD4+early), or 12 month after a suppressive therapy (DeltaCD4+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 naïve, time to reach undetectable plasma HIV RNA, treatment with PI vs NNRTI were associated with an early immunological recovery; the occurrence of previous AIDS event, a history of injection drug use, and HCV infection were associated with failure to achieve an early immunological recovery. Variables associated with DeltaCD4+late immune recovery were baseline CD4+ value, plasma HIV RNA (both baseline as highest value), being naïve 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 being infected 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.
authors.affiliation: Servizio Biometria ed Epidemiologia Clinica - Direzione Scientifica - Fondazione IRCCS Policlinico San Matteo, 27100 Pavia, Italy. e.seminari@smatteo.pv.it
authors.forename: Elena
authors.initials: E
authors.lastname: Seminari
authors.forename: Carmine
authors.initials: C
authors.lastname: Tinelli
authors.forename: Giovanni
authors.initials: G
authors.lastname: Ravasi
authors.forename: Diego
authors.initials: D
authors.lastname: Ripamonti
authors.forename: Nicoletta
authors.initials: N
authors.lastname: Ladisa
authors.forename: Nicoletta
authors.initials: N
authors.lastname: Marino
authors.forename: Laura
authors.initials: L
authors.lastname: Sighinolfi
authors.forename: Placido
authors.initials: P
authors.lastname: Mondello
authors.forename: Marco
authors.initials: M
authors.lastname: Migliorino
authors.forename: Giampiero
authors.initials: G
authors.lastname: Carosi
authors.forename: Renato
authors.initials: R
authors.lastname: Maserati
mesh_terms: D000328:Adult; D019380:Anti-HIV Agents / Q000627:therapeutic use*; D023241:Antiretroviral Therapy, Highly Active; D018791:CD4 Lymphocyte Count; D005260:Female; D005838:Genotype; D015658:HIV Infections / Q000150:complications* / Q000188:drug therapy / Q000276:immunology*; D016174:Hepacivirus / Q000145:classification / Q000235:genetics / Q000302:isolation & purification; D006526:Hepatitis C / Q000150:complications* / Q000276:immunology* / Q000821:virology; D018937:Hepatitis C Antibodies / Q000097:blood; D006801:Humans; D008137:Longitudinal Studies; D008297:Male; D008875:Middle Aged; D016896:Treatment Outcome; D019562:Viral Load
chemical_list: D019380:Anti-HIV Agents; D018937:Hepatitis C Antibodies