Determinants of suboptimal CD4+ T cell recovery after antiretroviral therapy initiation in a prospective cohort of acute HIV‐1 infection
Year: 2020
Type: article
Study design: Observational Study
Abstract: Introduction Up to 30% of individuals treated with antiretroviral therapy (ART) during chronic HIV fail to recover CD4 counts to >500 cells/mm3 despite plasma viral suppression. We investigated the frequency and associations of suboptimal CD4 recovery after ART started during acute HIV infection (AHI). Methods Participants who started ART in Fiebig I to V AHI with ≥48 weeks of continuous documented HIV‐RNA < 50 copies/mL were stratified by CD4 count at latest study visit to suboptimal immune recovery (SIR; CD4 < 350 cells/mm3), intermediate immune recovery (IIR; 350 ≤ CD4 < 500) and complete immune recovery (CIR; CD4 ≥ 500). Clinical and laboratory parameters were assessed at pre‐ART baseline and latest study visit. Additional inflammatory and neurobehavioral endpoints were examined at baseline and 96 weeks. Results Of 304 participants (96% male, median 26 years old) evaluated after median 144 (range 60 to 420) weeks of ART initiated at median 19 days (range 1 to 62) post‐exposure, 3.6% (n = 11) had SIR and 14.5% (n = 44) had IIR. Pre‐ART CD4 count in SIR compared to CIR participants was 265 versus 411 cells/mm3 (p = 0.002). Individuals with SIR or IIR had a slower CD4 rate of recovery compared to those with CIR. Timing of ART initiation by Fiebig stage did not affect CD4 count during treatment. Following ART, the CD8+T cell count (p = 0.001) and CD4/CD8 ratio (p = 0.047) were lower in SIR compared to CIR participants. Compared to the CIR group at week 96, the combined SIR and IIR groups had higher sCD14 (p = 0.008) and lower IL‐6 (p = 0.04) in plasma, without differences in neuropsychological or psychiatric indices. Conclusions Despite immediate and sustained treatment in AHI, suboptimal CD4 recovery occurs uncommonly and is associated with low pre‐ART CD4 count as well as persistent low CD8 count and CD4/CD8 ratio during treatment.
DOI: 10.1002/jia2.25585
Authors: Ryan Handoko, Donn J Colby, Eugène Kroon, Carlo Sacdalan, Mark de Souza, Suteeraporn Pinyakorn, Peeriya Prueksakaew, Chutharat Munkong, Sasiwimol Ubolyam, Siriwat Akapirat, Jennifer Chiarella, Shelly Krebs, Irini Sereti, Victor Valcour, Robert Paul, Nelson L. Michael, Nittaya Phanuphak, Jintanat Ananworanich, Serena Spudich, the SEARCH 010/RV254 Study Team
Institutions: Yale University, Thai Red Cross Society, Walter Reed Army Institute of Research, Henry M. Jackson Foundation, HIV Netherlands Australia Thailand Research Collaboration, Armed Forces Research Institute of Medical Science, United States Army Medical Directorate - Armed Forces Research Institute of Medical Sciences, National Institutes of Health, National Institute of Allergy and Infectious Diseases, University of California, San Francisco, University of Missouri–St. Louis, Missouri Institute of Mental Health
Language: English
Topic: HIV Research and Treatment
Subfield: Virology
Field: Immunology and Microbiology
Domain: Life Sciences
Open Access status: gold
Estimated APC paid: $2,400
Funders: Merck, Gilead Sciences, Division of Intramural Research, National Institute of Allergy and Infectious Diseases, ViiV Healthcare, National Institutes of Health, National Heart, Lung, and Blood Institute, National Institute of Mental Health, National Institute of Neurological Disorders and Stroke, National Center for Advancing Translational Sciences, U.S. Military HIV Research Program
Awards: G1103249167, Therapeutic Interventions during Acute Infection to Address the CNS Reservoir for, G2967393742, Long-Term CNS Consequences of Treatment During Acute Infection, G4326145199, Short Term Research Training: Students in Health Professional Schools, Yale Clinical and Translational Science Award
OpenAlex ID: W3087489697