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. 2020 Sep;23(9):e25585.
doi: 10.1002/jia2.25585.

Determinants of suboptimal CD4+ T cell recovery after antiretroviral therapy initiation in a prospective cohort of acute HIV-1 infection

Ryan Handoko  1 , Donn J Colby  2   3 , Eugène Kroon  2 , Carlo Sacdalan  2 , Mark de Souza  2 , Suteeraporn Pinyakorn  2   3   4 , Peeriya Prueksakaew  2 , Chutharat Munkong  2 , Sasiwimol Ubolyam  5 , Siriwat Akapirat  6 , Jennifer Chiarella  1 , Shelly Krebs  3   4 , Irini Sereti  7 , Victor Valcour  8 , Robert Paul  9 , Nelson L Michael  3 , Nittaya Phanuphak  2 , Jintanat Ananworanich  2   3   4 , Serena Spudich  1 ; SEARCH 010/RV254 Study Team
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Determinants of suboptimal CD4+ T cell recovery after antiretroviral therapy initiation in a prospective cohort of acute HIV-1 infection

Ryan Handoko et al. J Int AIDS Soc. 2020 Sep.

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.

Keywords: ARV; Asia; HIV care continuum; LMIC; immunology; men who have sex with men.

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Figures

Figure 1
Figure 1
Longitudinal CD4+ T cell counts of participants with acute HIV infection according to suboptimal, intermediate and complete immune recovery groups. (A) Mean CD4+ T cell counts of all participants (black) and by suboptimal (red), intermediate (green) and complete immune recovery (blue) groups. Dotted black line represents the total number of participants across all recovery groups at each study visit week. B‐D, CD4+ T cell counts of participants in suboptimal (B), intermediate (C) and complete (D) recovery groups. Solid lines represent the mean CD4+ T cell count at each follow‐up study visit week. Dashed lines represent the 95% confidence interval of CD4+ T cell counts at each study visit week. Dotted black lines represent the total number of participants in each respective recovery group at each study visit week
Figure 2
Figure 2
CD4+ T cell count by Fiebig stage at enrolment. Violin plots of CD4 count at baseline (A) and at latest study visit (B) by Fiebig stage at enrolment. (C), Violin plot of change in CD4 count between baseline and latest study visit by Fiebig stage at enrolment. Comparison between groups by Kruskal–Wallis test. ****p < 0.0001, ns indicates not statistically significant
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