title: Comparative Impact of Suppressive Antiretroviral Regimens on the CD4/CD8 T-Cell Ratio: A Cohort Study.
abstract: Although different factors have been implicated in the CD4/CD8 T-cell ratio recovery in HIV-infected patients who receive effective antiretroviral therapy (ART), limited information exists on the influence of the regimen composition. A longitudinal study carried out in a prospective, single-center cohort of HIV-infected patients. ART regimens including non-nucleoside reverse transcriptase inhibitors (NNRTI), protease inhibitors (PI), or integrase strand transfer inhibitors (INSTI) from patients who achieved long-term (≥6-month duration) virological suppression (HIV-RNA < 400 copies/mL) from January 1998 to June 2014 were analyzed. The impact of ART composition on the changes of the CD4/CD8 T-cell ratio was modeled using a mixed linear approach with adjustment for possible confounders. A total of 1068 ART regimens from 570 patients were analyzed. Mean (SD) age of the patients was 42.15 (10.68) years and 276 (48.42%) had hepatitis C virus (HCV) coinfection. Five hundred fifty-eight (52.25%) regimens were PI-based, 439 (40.10%) NNRTI-based, and 71 (6.65%) INSTI-based; 487 (45.60%) were initial regimens, 476 (44.57%) simplification, and 105 (9.83%) salvage regimens. Median (IQR) number of regimens was 1 (1-2) per patient, of 29 (14-58) months duration, and 4 (3-7) CD4/CD8 measurements per regimen. The median baseline CD4/CD8 ratio was 0.42, 0.50, and 0.54, respectively, with the PI-, NNRTI-, and INSTI-based regimens (P = 0.0073). Overall median (IQR) increase of CD4/CD8 ratio was 0.0245 (-0.0352-0.0690) per year, and a CD4/CD8 ratio ≥1 was achieved in 19.35% of the cases with PI-based, 25.97% with NNRTI-based, and 22.54% with INSTI-based regimens (P = 0.1406). In the adjusted model, the mean CD4/CD8 T-cell ratio increase was higher with NNRTI-based regimens compared for PI-based (estimated coefficient for PI [95% CI], -0.0912 [-0.1604 to -0.0219], P = 0.009). Also, a higher CD4/CD8 baseline ratio was associated with higher CD4/CD8 increase in the adjusted model (P = 0.001); by contrast, higher age (P = 0.020) and simplification of ART regimen (P = 0.003) had a negative impact on the CD4/CD8 ratio. Antiretroviral regimen composition has a differential impact on the CD4/CD8 T-cell ratio; NNRTI-based regimens are associated with enhanced CD4/CD8 T-cell ratio recovery compared to PI-based antiretroviral regimens.
authors.affiliation: From the Infectious Diseases Unit, Hospital General de Elche (MM, SP, GT, FL, FG), Universidad Miguel Hernández, Spain; and Statistics (XB, MS), Centro de Investigación Operativa, Universidad Miguel Hernández, Elche, Alicante, Spain.
authors.forename: Mar
authors.initials: M
authors.lastname: Masiá
authors.forename: Sergio
authors.initials: S
authors.lastname: Padilla
authors.forename: Xavier
authors.initials: X
authors.lastname: Barber
authors.forename: Marina
authors.initials: M
authors.lastname: Sanchis
authors.forename: Gertrudis
authors.initials: G
authors.lastname: Terol
authors.forename: Fernando
authors.initials: F
authors.lastname: Lidón
authors.forename: Félix
authors.initials: F
authors.lastname: Gutiérrez
mesh_terms: D000328:Adult; D000367:Age Factors; D000480:Alkynes; D000069446:Atazanavir Sulfate / Q000627:therapeutic use; D048588:Benzoxazines / Q000627:therapeutic use; D016516:CD4-CD8 Ratio; D060085:Coinfection / Q000276:immunology; D003521:Cyclopropanes; D004359:Drug Therapy, Combination / Q000379:methods; D005260:Female; D015658:HIV Infections / Q000188:drug therapy* / Q000276:immunology; D019428:HIV Integrase Inhibitors / Q000627:therapeutic use*; D017320:HIV Protease Inhibitors / Q000627:therapeutic use*; D006526:Hepatitis C / Q000188:drug therapy / Q000276:immunology; D006801:Humans; D007370:Interferon Type I / Q000627:therapeutic use; D008297:Male; D008875:Middle Aged; D009842:Oligopeptides / Q000627:therapeutic use; D000068898:Raltegravir Potassium / Q000627:therapeutic use; D018894:Reverse Transcriptase Inhibitors / Q000627:therapeutic use*; D012254:Ribavirin / Q000627:therapeutic use; D019438:Ritonavir / Q000627:therapeutic use
chemical_list: D000480:Alkynes; D048588:Benzoxazines; D003521:Cyclopropanes; D019428:HIV Integrase Inhibitors; D017320:HIV Protease Inhibitors; D007370:Interferon Type I; D009842:Oligopeptides; D018894:Reverse Transcriptase Inhibitors; D000068898:Raltegravir Potassium; D012254:Ribavirin; D000069446:Atazanavir Sulfate; C486464:telaprevir; C098320:efavirenz; D019438:Ritonavir