Impact of first-line antiretroviral therapy regimens on the restoration of the CD4/CD8 ratio in the CNICS cohort

on behalf of the CFAR Network of Integrated Clinical Systems (CNICS)

Research output: Contribution to journalArticlepeer-review

10 Scopus citations

Abstract

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 cutoff of 1.0 than a PI-based regimen, which might have clinical implications.

Original languageEnglish (US)
Pages (from-to)1604-1610
Number of pages7
JournalJournal of antimicrobial chemotherapy
Volume75
Issue number6
DOIs
StatePublished - 2021

Funding

S.S.-V. has received personal fees from ViiV Healthcare, Janssen, Gilead and MSD and grants from MSD and Gilead. S.M. has received personal fees from ViiV Healthcare, Janssen, Gilead and MSD and grants from MSD, ViiV Healthcare and Gilead. C.J.A. has received speaking fees from ViiV Healthcare and a grant from Gilead. All other authors: none to declare. CNICS is an NIH-funded programme (R24 AI067039) made possible by National Institute of Allergy and Infectious Diseases (NIAID): University of Alabama (P30 AI027767), University of Washington (P30 AI027757), University of California, San Diego (P30 AI036214), University of California, San Francisco (P30 AI027763), Case Western Reserve University (P30 AI036219), Johns Hopkins University (P30 AI094189, U01 DA036935), Fenway Health/Harvard (P30 AI060354) and University of North Carolina (P30 AI50410).

ASJC Scopus subject areas

  • Pharmacology
  • Microbiology (medical)
  • Pharmacology (medical)
  • Infectious Diseases

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