Individual Differences in CD4/CD8 T-Cell Ratio Trajectories and Associated Risk Profiles Modeled From Acute HIV Infection

Abstract

ObjectiveWe 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.MethodsA 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.ResultsParticipants 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.ConclusionsEarly 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.

The Interaction of HIV With Mental Health in the Modern Antiretroviral Therapy Era

“…These findings build on prior research where social isolation was linked to higher viral load in plasma and cerebrospinal fluid, greater CD4+ T-cell count declines, and more CD4+ and CD8+ T-cell activation in pigtailed macaques during acute SIV infection ( 37 ). The translational implications of these experimental SIV studies are supported by results from the study by Paul and colleagues ( 38 ) in this issue where poorer mental health and reduced neurocognitive functioning at the time of acute HIV diagnosis independently predicted slower CD4+ T-cell recovery after suppressive ART in the RV254/SEARCH 010 Thai cohort study. These studies highlight the importance of well-characterized acute HIV cohorts to better understand how mental health and substance use in the period surrounding HIV infection could influence set points for immunologic responses to ART.…”

Impact of Latent M. tuberculosis Infection Treatment on Time to CD4/CD8 Recovery in Acute, Recent, and Chronic HIV Infection

“…51 Conversely, in a single-center cohort study conducted in Bangkok between 2009 and 2020 of 483 AIH patients who began ART during Fiebig I-V, it was observed that early HIV disease dynamics predicted an unfavorable CD4/CD8 T-cell ratio recovery after ART, suggesting that adjunctive strategies should be considered to achieve immune normalization. 52…”

“…51 Conversely, in a single-center cohort study conducted in Bangkok between 2009 and 2020 of 483 AIH patients who began ART during Fiebig I-V, it was observed that early HIV disease dynamics predicted an unfavorable CD4/CD8 T-cell ratio recovery after ART, suggesting that adjunctive strategies should be considered to achieve immune normalization. 52 Brazil was the first LMIC to adopt the "treat all" recommendation and to provide HIV pre-exposure prophylaxis (PrEP) for those with high HIV vulnerability free of charge through the national public health system. Yet, these interventions have been insufficient to halt the epidemic.…”

Brain volumetrics differ by Fiebig stage in acute HIV infection

“…1-2 weeks after infection) as a critical period for cytokine induction and establishment of peak viremia [16][17][18][19]. Work from RV254/SEARCH010, a prospectively enrolled cohort of participants with acute HIV infection (AHI) followed before and after ART commenced during acute infection, reveals higher viral burden, immune activation, T-cell depletion, and incidence of acute retroviral syndrome among individuals who initiate ART after Fiebig stages I and II [17,18,[20][21][22]. Although some of these disease processes have been linked to variations in brain volume in primary or chronic HIV [9,[23][24][25][26], it remains unknown whether brain volumes differ by Fiebig stage (i.e.…”