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Individual Differences in CD4/CD8 T-Cell Ratio Trajectories and Associated Risk Profiles Modeled From Acute HIV
Robert Paul1, Kyu Cho, Jacob Bolzenius
1From the Department of Psychological Sciences (Paul) and Missouri Institute of Mental Health (Cho, Bolzenius), University of Missouri, St. Louis, Missouri; SEARCH (Sacdalan, Tipsuk, Suttichom, Phanuphak, Chan, Kroon, Sriplienchan), Institute of HIV Research and Innovation (IHRI), Bangkok, Thailand; Department of Medicine, Division of Infectious Diseases (Ndhlovu, Premeaux), Weill Cornell Medicine, New York City, New York; Vaccine and Gene Therapy Institute (Trautmann), Oregon Health and Science University, Beaverton, Oregon; U.S. Military HIV Research Program (Krebs, Crowell, Colby, Vasan, Hsu, Robb, Ake), Walter Reed Army Institute of Research, Silver Spring; Henry M. Jackson Foundation for the Advancement of Military Medicine, Inc. (Krebs, Crowell, Colby, Vasan, Hsu, Robb), Inc., Bethesda, Maryland; Department of Neurology (Chan, Spudich), Yale University School of Medicine, New Haven, Connecticut; Department of Public Health Sciences (Carrico), University of Miami Miller School of Medicine, Miami, Florida; Memory and Aging Center, Department of Neurology (Valcour), University of California, San Francisco, California; Department of Global Health, Amsterdam Medical Center (Ananworanich), University of Amsterdam, Amsterdam, the Netherlands.
Objective:
We examined individual differences in CD4/CD8 T-cell ratio trajectories and associated risk profiles from acute HIV infection (AHI) through 144 weeks of antiretroviral therapy (ART) using a data-driven approach.
Methods:
A total of 483 AHI participants began ART during Fiebig I-V and completed follow-up evaluations for 144 weeks. CD4+, CD8+, and CD4/CD8 T-cell ratio trajectories were defined followed by analyses to identify associated risk variables.
Results:
Participants had a median viral load (VL) of 5.88 copies/ml and CD4/CD8 T-cell ratio of 0.71 at enrollment. After 144 weeks of ART, the median CD4/CD8 T-cell ratio was 1.3. Longitudinal models revealed five CD4/CD8 T-cell ratio subgroups: group 1 (3%) exhibited a ratio >1.0 at all visits; groups 2 (18%) and 3 (29%) exhibited inversion at enrollment, with normalization 4 and 12 weeks after ART, respectively; and groups 4 (31%) and 5 (18%) experienced CD4/CD8 T-cell ratio inversion due to slow CD4+ T-cell recovery (group 4) or high CD8+ T-cell count (group 5). Persistent inversion corresponded to ART onset after Fiebig II, higher VL, soluble CD27 and TIM-3, and lower eosinophil count. Individuals with slow CD4+ T-cell recovery exhibited higher VL, lower white blood cell count, lower basophil percent, and treatment with standard ART, as well as worse mental health and cognition, compared with individuals with high CD8+ T-cell count.
Conclusions:
Early HIV disease dynamics predict unfavorable CD4/CD8 T-cell ratio outcomes after ART. CD4+ and CD8+ T-cell trajectories contribute to inversion risk and correspond to specific viral, immune, and psychological profiles during AHI. Adjunctive strategies to achieve immune normalization merit consideration.
