TY - JOUR
T1 - Impact of first-line antiretroviral therapy regimens on the restoration of the CD4/CD8 ratio in the CNICS cohort
AU - on behalf of the CFAR Network of Integrated Clinical Systems (CNICS)
AU - Herrera, Sabina
AU - Fernandez-Felix, Borja M.
AU - Hunt, Peter W.
AU - Deeks, Steven G.
AU - Sainz, Talía
AU - Heath, Sonya L.
AU - Achenbach, Chad J.
AU - Rodríguez, Benigno
AU - Mathews, Christopher
AU - Christopoulos, Katerina
AU - Mayer, Kenneth
AU - Napravnik, Sonia
AU - Moreno, Santiago
AU - Serrano-Villar, Sergio
N1 - Funding Information:
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.
Funding Information:
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).
Publisher Copyright:
© The Author(s) 2020.
PY - 2021
Y1 - 2021
N2 - 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.
AB - 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.
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U2 - 10.1093/JAC/DKAA024
DO - 10.1093/JAC/DKAA024
M3 - Article
C2 - 32211777
AN - SCOPUS:85084784231
SN - 0305-7453
VL - 75
SP - 1604
EP - 1610
JO - Journal of Antimicrobial Chemotherapy
JF - Journal of Antimicrobial Chemotherapy
IS - 6
ER -