Dataset Information

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

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.

SUBMITTER: Handoko R

PROVIDER: S-EPMC7507109 | biostudies-literature | 2020 Sep

REPOSITORIES: biostudies-literature

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Publications

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

Handoko Ryan R Colby Donn J DJ Kroon Eugène E Sacdalan Carlo C de Souza Mark M Pinyakorn Suteeraporn S Prueksakaew Peeriya P Munkong Chutharat C Ubolyam Sasiwimol S Akapirat Siriwat S Chiarella Jennifer J Krebs Shelly S Sereti Irini I Valcour Victor V Paul Robert R Michael Nelson L NL Phanuphak Nittaya N Ananworanich Jintanat J Spudich Serena S

Journal of the International AIDS Society 20200901 9

<h4>Introduction</h4>Up to 30% of individuals treated with antiretroviral therapy (ART) during chronic HIV fail to recover CD4 counts to >500 cells/mm<sup>3</sup> despite plasma viral suppression. We investigated the frequency and associations of suboptimal CD4 recovery after ART started during acute HIV infection (AHI).<h4>Methods</h4>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 visi ...[more]

PMID: 32949118

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Project description:BackgroundCD4+ cell count recovery after effective antiretroviral therapy (ART) is an important determinant of both AIDS and non-AIDS morbidity and mortality. Data on CD4+ cell count recovery after initiation of ART are still limited in Sub-Saharan Africa. The aim of this study was to assess CD4+ cell count recovery among HIV-infected adults initiating ART in an Ethiopian setting.MethodsA retrospective cohort study of HIV-infected adults initiating ART between September 2008 and June 2019 was carried out. CD4+ cell count recovery was defined as an increase in CD4+ cell count of >100 cells/mm3 from baseline or achievement of a CD4+ cell count >500 cells/mm3 at 12 months after ART initiation. Factors associated with CD4+ cell count recovery were evaluated using logistic regression analysis.ResultsOf the 566 patients included in this study, the median baseline CD4+ cell count was 264 cells/mm3 (IQR: 192-500). At 12 months after ART initiation, the median CD4+ cell count increased to 472 cells/mm3, and the proportion of patients with CD4+ cell count < 200 cells/mm3 declined from 28.3 to 15.0%. A total of 58.0% of patients had an increase in CD4+ cell count of >100 cells/mm3 from baseline and 48.6% achieved a CD4+ cell count >500 cells/mm3 at 12 months. Among patients with CD4+ cell counts < 200, 200-350 and >350 cells/mm3 at baseline, respectively, 30%, 43.9% and 61.7% achieved a CD4+ cell count >500 cells/mm3 at 12 months. In multivariable analysis, poor CD4+ cell count recovery (an increase of ≤100 cells/mm3 from baseline) was associated with older age, male sex, higher baseline CD4+ cell count and zidovudine-containing initial regimen. Factors associated with poor CD4+ cell count recovery to reach the level >500 cells/mm3 included older age, male sex and lower baseline CD4+ cell count.ConclusionsCD4+ cell count failed to recover in a substantial proportion of adults initiating ART in this resource-limited setting. Older age, male sex and baseline CD4+ cell count are the dominant factors for poor CD4+ cell count recovery. Novel therapeutic approaches are needed focusing on high risk patients to maximize CD4+ cell count recovery and improve outcomes during therapy.

Project description:BackgroundThe relationship between the timing of the initiation of antiretroviral therapy (ART) after infection with human immunodeficiency virus type 1 (HIV-1) and the recovery of CD4+ T-cell counts is unknown.MethodsIn a prospective, observational cohort of persons with acute or early HIV-1 infection, we determined the trajectory of CD4+ counts over a 48-month period in partially overlapping study sets: study set 1 included 384 participants during the time window in which they were not receiving ART and study set 2 included 213 participants who received ART soon after study entry or sometime thereafter and had a suppressed plasma HIV viral load. We investigated the likelihood and rate of CD4+ T-cell recovery to 900 or more cells per cubic millimeter within 48 months while the participants were receiving viral-load-suppressive ART.ResultsAmong the participants who were not receiving ART, CD4+ counts increased spontaneously, soon after HIV-1 infection, from the level at study entry (median, 495 cells per cubic millimeter; interquartile range, 383 to 622), reached a peak value (median, 763 cells per cubic millimeter; interquartile range, 573 to 987) within approximately 4 months after the estimated date of infection, and declined progressively thereafter. Recovery of CD4+ counts to 900 or more cells per cubic millimeter was seen in approximately 64% of the participants who initiated ART earlier (≤4 months after the estimated date of HIV infection) as compared with approximately 34% of participants who initiated ART later (>4 months) (P<0.001). After adjustment for whether ART was initiated when the CD4+ count was 500 or more cells per cubic millimeter or less than 500 cells per cubic millimeter, the likelihood that the count would increase to 900 or more cells per cubic millimeter was lower by 65% (odds ratio, 0.35), and the rate of recovery was slower by 56% (rate ratio, 0.44), if ART was initiated later rather than earlier. There was no association between the plasma HIV RNA level at the time of initiation of ART and CD4+ T-cell recovery.ConclusionsA transient, spontaneous restoration of CD4+ T-cell counts occurs in the 4-month time window after HIV-1 infection. Initiation of ART during this period is associated with an enhanced likelihood of recovery of CD4+ counts. (Funded by the National Institute of Allergy and Infectious Diseases and others.).

Project description:ObjectivesDespite sustained viral suppression with effective antiretroviral therapy (ART), HIV-infected patients with suboptimal immune recovery are still at high risk of both non-AIDS-related and AIDS-related events. The aim of this study was to investigate determinants potentially associated with suboptimal CD4 + T cell count recovery during free ART with sustained viral suppression among an HIV-infected Yi ethnicity population in Liangshan Prefecture, an area in China with high HIV prevalence.MethodsThis retrospective study included HIV-infected Yi adults (≥ 18 years and baseline CD4 + T cell count less than 500 cells/μL) for whom ART supported by National Free Antiretroviral Treatment Program was initiated between January 2015 and December 2018 in Zhaojue County, Liangshan Prefecture. Virological suppression (viral load < 50 copies/mL) was achieved within 12 months after ART initiation, and sustained virological suppression was maintained. Multivariate log-binomial regression analysis was used to assess determinants of suboptimal immune recovery.ResultsThere were 140 female and 137 male patients in this study, with a mean age of 36.57 ± 7.63 years. Most of the Yi patients were infected through IDU (48.7%) or heterosexual contact (49.8%), and the anti-HCV antibody prevalence was high (43.7%, 121/277). Of the 277 patients with a mean ART duration of 3.77 ± 1.21 years, complete immune recovery occurred in only 32.9%. The baseline CD4 + T cell count in patients with suboptimal and intermediate immune recovery was 248.64 ± 108.10 and 288.59 ± 108.86 cells/μL, respectively, which was much lower than the baseline 320.02 ± 123.65 cells/μL in patients who achieved complete immune recovery (p < 0.001). Multivariable analysis demonstrated that low pre-ART CD4 + cell count and coinfection with HCV were associated with immune recovery of the HIV patients.ConclusionsOur study suggests that for HIV-infected Yi patients in Liangshan Prefecture, prompt ART initiation after diagnosis of HIV infection should be applied, and curative HCV treatment should be given to patients with HCV/HIV coinfection to improve the immunological effectiveness of ART. Trial registration None.

Dataset Information

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

Introduction

Methods

Results

Conclusions

Publications

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

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets

Dataset Information

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

Introduction

Methods

Results

Conclusions

Publications

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

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets

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