BACKGROUND: The CD4/CD8 ratio is an indicator of immunosenescence and a predictor of all-cause mortality in HIV-infected patients. The effects of different ART regimens on CD4/CD8 ratio recovery remain unclear. METHODS: Clinical cohort study of ART-treated patients from the CFAR Network of Integrated Clinical Systems (CNICS). We included ART-naive adults with HIV infection who achieved undetectable HIV RNA during the first 48 weeks of treatment and had additional follow-up 48 weeks after virological suppression (VS). Primary endpoints included increase in CD4/CD8 ratio at both timepoints and secondary endpoints were CD4/CD8 ratio recovery at cut-offs of ≥0.5 or ≥1.0. RESULTS: Of 3971 subjects who met the study criteria, 1876 started ART with an NNRTI, 1804 with a PI and 291 with an integrase strand transfer inhibitor (INSTI). After adjusting for age, sex, race, year of entry, risk group, HCV serostatus, baseline viral load and baseline CD4/CD8 ratio, subjects on an NNRTI showed a significantly greater CD4/CD8 ratio gain compared with those on a PI, either 48 weeks after ART initiation or after 48 weeks of HIV RNA VS. The greater CD4/CD8 ratio improvement in the NNRTI arm was driven by a higher decline in CD8 counts. The INSTI group showed increased rates of CD4/CD8 ratio normalization at the ≥1.0 cut-off compared with the PI group. CONCLUSIONS: NNRTI therapy was associated with a greater increase in the CD4/CD8 ratio compared with PIs. NNRTI- and INSTI-based first-line ART were associated with higher rates of CD4/CD8 ratio normalization at a cut-off of 1.0 than a PI-based regimen, which might have clinical implications.
BACKGROUND: The CD4/CD8 ratio is an indicator of immunosenescence and a predictor of all-cause mortality in HIV-infectedpatients. The effects of different ART regimens on CD4/CD8 ratio recovery remain unclear. METHODS: Clinical cohort study of ART-treated patients from the CFAR Network of Integrated Clinical Systems (CNICS). We included ART-naive adults with HIV infection who achieved undetectable HIV RNA during the first 48 weeks of treatment and had additional follow-up 48 weeks after virological suppression (VS). Primary endpoints included increase in CD4/CD8 ratio at both timepoints and secondary endpoints were CD4/CD8 ratio recovery at cut-offs of ≥0.5 or ≥1.0. RESULTS: Of 3971 subjects who met the study criteria, 1876 started ART with an NNRTI, 1804 with a PI and 291 with an integrase strand transfer inhibitor (INSTI). After adjusting for age, sex, race, year of entry, risk group, HCV serostatus, baseline viral load and baseline CD4/CD8 ratio, subjects on an NNRTI showed a significantly greater CD4/CD8 ratio gain compared with those on a PI, either 48 weeks after ART initiation or after 48 weeks of HIV RNA VS. The greater CD4/CD8 ratio improvement in the NNRTI arm was driven by a higher decline in CD8 counts. The INSTI group showed increased rates of CD4/CD8 ratio normalization at the ≥1.0 cut-off compared with the PI group. CONCLUSIONS: NNRTI therapy was associated with a greater increase in the CD4/CD8 ratio compared with PIs. NNRTI- and INSTI-based first-line ART were associated with higher rates of CD4/CD8 ratio normalization at a cut-off of 1.0 than a PI-based regimen, which might have clinical implications.
Authors: Polyana Monteiro; Iñaki Perez; Montserrat Laguno; Maria Martínez-Rebollar; Ana González-Cordon; Montserrat Lonca; Josep Mallolas; Jose L Blanco; Jose M Gatell; Esteban Martínez Journal: J Antimicrob Chemother Date: 2013-10-14 Impact factor: 5.790
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Authors: Sine Reker Hadrup; Jan Strindhall; Tania Køllgaard; Tina Seremet; Boo Johansson; Graham Pawelec; Per thor Straten; Anders Wikby Journal: J Immunol Date: 2006-02-15 Impact factor: 5.422
Authors: Marie Helleberg; Gitte Kronborg; Henrik Ullum; Lars P Ryder; Niels Obel; Jan Gerstoft Journal: J Infect Dis Date: 2014-12-08 Impact factor: 5.226
Authors: F De Salvador-Guillouët; C Sakarovitch; J Durant; K Risso; E Demonchy; P M Roger; E Fontas Journal: PLoS One Date: 2015-10-20 Impact factor: 3.240
Authors: Sergio Serrano-Villar; Talia Sainz; Sulggi A Lee; Peter W Hunt; Elizabeth Sinclair; Barbara L Shacklett; April L Ferre; Timothy L Hayes; Ma Somsouk; Priscilla Y Hsue; Mark L Van Natta; Curtis L Meinert; Michael M Lederman; Hiroyu Hatano; Vivek Jain; Yong Huang; Frederick M Hecht; Jeffrey N Martin; Joseph M McCune; Santiago Moreno; Steven G Deeks Journal: PLoS Pathog Date: 2014-05-15 Impact factor: 6.823