Risk Factors for Low CD4+ Count Recovery Despite Viral Suppression among Participants Initiating Antiretroviral Treatment with CD4+ Counts > 500 Cells/mm3: Findings from the Strategic Timing of AntiRetroviral Therapy (START) Trial

INSIGHT START Study Group

doi:10.1097/QAI.0000000000001967

Risk Factors for Low CD4⁺ Count Recovery Despite Viral Suppression among Participants Initiating Antiretroviral Treatment with CD4⁺ Counts > 500 Cells/mm³: Findings from the Strategic Timing of AntiRetroviral Therapy (START) Trial

INSIGHT START Study Group

Biostatistics

Research output: Contribution to journal › Article › peer-review

14 Scopus citations

Abstract

BACKGROUND: Low CD4 recovery among HIV-positive individuals who achieve virologic suppression is common but has not been studied among individuals initiating treatment at CD4 counts of >500 cells/mm.

SETTING: United States, Africa, Asia, Europe and Israel, Australia, Latin America.

METHODS: Among participants randomized to immediate antiretroviral therapy (ART) in the Strategic Timing of AntiRetroviral Therapy trial, low CD4 recovery was defined as a CD4 increase of <50 cells/mm from baseline after 8 months despite viral load of ≤200 copies/mL. Risk factors for low recovery were investigated with logistic regression.

RESULTS: Low CD4 recovery was observed in 39.7% of participants. Male sex [odds ratio (OR), 1.53; P = 0.007], lower screening CD4 cell counts (OR, 1.09 per 100 fewer cells/mm; P = 0.004), higher baseline CD8 cell counts (OR, 1.05 per 100 more cells/mm; P < 0.001), and lower HIV RNA levels (OR, 1.93 per log10 decrease; P < 0.001) were associated with low CD4 recovery. D-dimer had a quadratic association with low CD4 recovery, with lowest odds occurring at 0.32 μg/mL. At lower HIV RNA levels, the odds of low CD4 recovery were elevated across the levels of screening CD4 count; but at higher HIV RNA levels, the odds of low CD4 recovery were higher among those with lower vs. higher screening CD4.

CONCLUSIONS: Low CD4 recovery is frequent among participants starting ART at high CD4 counts. Risk factors include male sex, lower screening CD4 cell counts, higher CD8 cell counts, and lower HIV RNA levels. More follow-up is required to determine the impact of low CD4 recovery on clinical outcomes.

Original language	English (US)
Pages (from-to)	10-17
Number of pages	8
Journal	Journal of Acquired Immune Deficiency Syndromes
Volume	81
Issue number	1
DOIs	https://doi.org/10.1097/QAI.0000000000001967
State	Published - May 1 2019

Bibliographical note

Funding Information:
Supported by the National Institutes of Health Grants UM1-AI068641 and UM1-AI120197. Supported by the National Institute of Allergy and Infectious Diseases, National Institutes of Health Clinical Center, National Cancer Institute, National Heart, Lung, and Blood Institute, Eunice Kennedy Shriver National Institute of Child Health and Human Development, National Institute of Mental Health, National Institute of Neurological Disorders and Stroke, National Institute of Arthritis and Musculoskeletal and Skin Diseases, Agence Nationale de Recherches sur le SIDA et les Hépatites Virales (France), National Health and Medical Research Council (Australia), National Research Foundation (Denmark), Bundes ministerium für Bildung und Forschung (Germany), European AIDS Treatment Network, Medical Research Council (United Kingdom), National Institute for Health Research, National Health Service (United Kingdom), and University of Minnesota. Antiretroviral drugs were donated to the central drug repository by AbbVie, Bristol-Myers Squibb, Gilead Sciences, GlaxoSmithKline/ViiV Healthcare, Janssen Scientific Affairs, and Merck.

Publisher Copyright:
Copyright © 2019 Wolters Kluwer Health, Inc. All rights reserved.

Keywords

CD4
HIV
antiretroviral therapy
immune response
Humans
Risk Factors
Anti-HIV Agents/therapeutic use
Logistic Models
Male
HIV Infections/drug therapy
CD4 Lymphocyte Count/statistics & numerical data
Treatment Failure
Sex Factors
Adult
Female
CD4-Positive T-Lymphocytes/drug effects

PubMed: MeSH publication types

Research Support, Non-U.S. Gov't
Randomized Controlled Trial
Journal Article
Research Support, N.I.H., Extramural

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

Publisher link

10.1097/QAI.0000000000001967

https://boris.unibe.ch/125454/1/00126334-900000000-96469.pdf

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INSIGHT START Study Group (2019). Risk Factors for Low CD4⁺ Count Recovery Despite Viral Suppression among Participants Initiating Antiretroviral Treatment with CD4⁺ Counts > 500 Cells/mm³: Findings from the Strategic Timing of AntiRetroviral Therapy (START) Trial. Journal of Acquired Immune Deficiency Syndromes, 81(1), 10-17. https://doi.org/10.1097/QAI.0000000000001967

Risk Factors for Low CD4⁺ Count Recovery Despite Viral Suppression among Participants Initiating Antiretroviral Treatment with CD4⁺ Counts > 500 Cells/mm³: Findings from the Strategic Timing of AntiRetroviral Therapy (START) Trial. / INSIGHT START Study Group.
In: Journal of Acquired Immune Deficiency Syndromes, Vol. 81, No. 1, 01.05.2019, p. 10-17.

Research output: Contribution to journal › Article › peer-review

INSIGHT START Study Group 2019, 'Risk Factors for Low CD4⁺ Count Recovery Despite Viral Suppression among Participants Initiating Antiretroviral Treatment with CD4⁺ Counts > 500 Cells/mm³: Findings from the Strategic Timing of AntiRetroviral Therapy (START) Trial', Journal of Acquired Immune Deficiency Syndromes, vol. 81, no. 1, pp. 10-17. https://doi.org/10.1097/QAI.0000000000001967

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title = "Risk Factors for Low CD4+ Count Recovery Despite Viral Suppression among Participants Initiating Antiretroviral Treatment with CD4+ Counts > 500 Cells/mm3: Findings from the Strategic Timing of AntiRetroviral Therapy (START) Trial",

abstract = "BACKGROUND: Low CD4 recovery among HIV-positive individuals who achieve virologic suppression is common but has not been studied among individuals initiating treatment at CD4 counts of >500 cells/mm.SETTING: United States, Africa, Asia, Europe and Israel, Australia, Latin America.METHODS: Among participants randomized to immediate antiretroviral therapy (ART) in the Strategic Timing of AntiRetroviral Therapy trial, low CD4 recovery was defined as a CD4 increase of <50 cells/mm from baseline after 8 months despite viral load of ≤200 copies/mL. Risk factors for low recovery were investigated with logistic regression.RESULTS: Low CD4 recovery was observed in 39.7% of participants. Male sex [odds ratio (OR), 1.53; P = 0.007], lower screening CD4 cell counts (OR, 1.09 per 100 fewer cells/mm; P = 0.004), higher baseline CD8 cell counts (OR, 1.05 per 100 more cells/mm; P < 0.001), and lower HIV RNA levels (OR, 1.93 per log10 decrease; P < 0.001) were associated with low CD4 recovery. D-dimer had a quadratic association with low CD4 recovery, with lowest odds occurring at 0.32 μg/mL. At lower HIV RNA levels, the odds of low CD4 recovery were elevated across the levels of screening CD4 count; but at higher HIV RNA levels, the odds of low CD4 recovery were higher among those with lower vs. higher screening CD4.CONCLUSIONS: Low CD4 recovery is frequent among participants starting ART at high CD4 counts. Risk factors include male sex, lower screening CD4 cell counts, higher CD8 cell counts, and lower HIV RNA levels. More follow-up is required to determine the impact of low CD4 recovery on clinical outcomes.",

keywords = "CD4, HIV, antiretroviral therapy, immune response, Humans, Risk Factors, Anti-HIV Agents/therapeutic use, Logistic Models, Male, HIV Infections/drug therapy, CD4 Lymphocyte Count/statistics & numerical data, Treatment Failure, Sex Factors, Adult, Female, CD4-Positive T-Lymphocytes/drug effects",

author = "{INSIGHT START Study Group} and Baker, {Jason V.} and Jeff Boatman and Hansjakob Furrer and Mushatt, {David M.} and Dalibor Sedl{\'a}{\v c}ek and Lundgren, {Jens D.} and Jim Neaton",

note = "Funding Information: Supported by the National Institutes of Health Grants UM1-AI068641 and UM1-AI120197. Supported by the National Institute of Allergy and Infectious Diseases, National Institutes of Health Clinical Center, National Cancer Institute, National Heart, Lung, and Blood Institute, Eunice Kennedy Shriver National Institute of Child Health and Human Development, National Institute of Mental Health, National Institute of Neurological Disorders and Stroke, National Institute of Arthritis and Musculoskeletal and Skin Diseases, Agence Nationale de Recherches sur le SIDA et les H{\'e}patites Virales (France), National Health and Medical Research Council (Australia), National Research Foundation (Denmark), Bundes ministerium f{\"u}r Bildung und Forschung (Germany), European AIDS Treatment Network, Medical Research Council (United Kingdom), National Institute for Health Research, National Health Service (United Kingdom), and University of Minnesota. Antiretroviral drugs were donated to the central drug repository by AbbVie, Bristol-Myers Squibb, Gilead Sciences, GlaxoSmithKline/ViiV Healthcare, Janssen Scientific Affairs, and Merck. Publisher Copyright: Copyright {\textcopyright} 2019 Wolters Kluwer Health, Inc. All rights reserved.",

year = "2019",

month = may,

day = "1",

doi = "10.1097/QAI.0000000000001967",

language = "English (US)",

volume = "81",

pages = "10--17",

journal = "Journal of Acquired Immune Deficiency Syndromes",

issn = "1525-4135",

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TY - JOUR

T1 - Risk Factors for Low CD4+ Count Recovery Despite Viral Suppression among Participants Initiating Antiretroviral Treatment with CD4+ Counts > 500 Cells/mm3

T2 - Findings from the Strategic Timing of AntiRetroviral Therapy (START) Trial

AU - INSIGHT START Study Group

AU - Baker, Jason V.

AU - Boatman, Jeff

AU - Furrer, Hansjakob

AU - Mushatt, David M.

AU - Sedláček, Dalibor

AU - Lundgren, Jens D.

AU - Neaton, Jim

N1 - Funding Information: Supported by the National Institutes of Health Grants UM1-AI068641 and UM1-AI120197. Supported by the National Institute of Allergy and Infectious Diseases, National Institutes of Health Clinical Center, National Cancer Institute, National Heart, Lung, and Blood Institute, Eunice Kennedy Shriver National Institute of Child Health and Human Development, National Institute of Mental Health, National Institute of Neurological Disorders and Stroke, National Institute of Arthritis and Musculoskeletal and Skin Diseases, Agence Nationale de Recherches sur le SIDA et les Hépatites Virales (France), National Health and Medical Research Council (Australia), National Research Foundation (Denmark), Bundes ministerium für Bildung und Forschung (Germany), European AIDS Treatment Network, Medical Research Council (United Kingdom), National Institute for Health Research, National Health Service (United Kingdom), and University of Minnesota. Antiretroviral drugs were donated to the central drug repository by AbbVie, Bristol-Myers Squibb, Gilead Sciences, GlaxoSmithKline/ViiV Healthcare, Janssen Scientific Affairs, and Merck. Publisher Copyright: Copyright © 2019 Wolters Kluwer Health, Inc. All rights reserved.

PY - 2019/5/1

Y1 - 2019/5/1

N2 - BACKGROUND: Low CD4 recovery among HIV-positive individuals who achieve virologic suppression is common but has not been studied among individuals initiating treatment at CD4 counts of >500 cells/mm.SETTING: United States, Africa, Asia, Europe and Israel, Australia, Latin America.METHODS: Among participants randomized to immediate antiretroviral therapy (ART) in the Strategic Timing of AntiRetroviral Therapy trial, low CD4 recovery was defined as a CD4 increase of <50 cells/mm from baseline after 8 months despite viral load of ≤200 copies/mL. Risk factors for low recovery were investigated with logistic regression.RESULTS: Low CD4 recovery was observed in 39.7% of participants. Male sex [odds ratio (OR), 1.53; P = 0.007], lower screening CD4 cell counts (OR, 1.09 per 100 fewer cells/mm; P = 0.004), higher baseline CD8 cell counts (OR, 1.05 per 100 more cells/mm; P < 0.001), and lower HIV RNA levels (OR, 1.93 per log10 decrease; P < 0.001) were associated with low CD4 recovery. D-dimer had a quadratic association with low CD4 recovery, with lowest odds occurring at 0.32 μg/mL. At lower HIV RNA levels, the odds of low CD4 recovery were elevated across the levels of screening CD4 count; but at higher HIV RNA levels, the odds of low CD4 recovery were higher among those with lower vs. higher screening CD4.CONCLUSIONS: Low CD4 recovery is frequent among participants starting ART at high CD4 counts. Risk factors include male sex, lower screening CD4 cell counts, higher CD8 cell counts, and lower HIV RNA levels. More follow-up is required to determine the impact of low CD4 recovery on clinical outcomes.

AB - BACKGROUND: Low CD4 recovery among HIV-positive individuals who achieve virologic suppression is common but has not been studied among individuals initiating treatment at CD4 counts of >500 cells/mm.SETTING: United States, Africa, Asia, Europe and Israel, Australia, Latin America.METHODS: Among participants randomized to immediate antiretroviral therapy (ART) in the Strategic Timing of AntiRetroviral Therapy trial, low CD4 recovery was defined as a CD4 increase of <50 cells/mm from baseline after 8 months despite viral load of ≤200 copies/mL. Risk factors for low recovery were investigated with logistic regression.RESULTS: Low CD4 recovery was observed in 39.7% of participants. Male sex [odds ratio (OR), 1.53; P = 0.007], lower screening CD4 cell counts (OR, 1.09 per 100 fewer cells/mm; P = 0.004), higher baseline CD8 cell counts (OR, 1.05 per 100 more cells/mm; P < 0.001), and lower HIV RNA levels (OR, 1.93 per log10 decrease; P < 0.001) were associated with low CD4 recovery. D-dimer had a quadratic association with low CD4 recovery, with lowest odds occurring at 0.32 μg/mL. At lower HIV RNA levels, the odds of low CD4 recovery were elevated across the levels of screening CD4 count; but at higher HIV RNA levels, the odds of low CD4 recovery were higher among those with lower vs. higher screening CD4.CONCLUSIONS: Low CD4 recovery is frequent among participants starting ART at high CD4 counts. Risk factors include male sex, lower screening CD4 cell counts, higher CD8 cell counts, and lower HIV RNA levels. More follow-up is required to determine the impact of low CD4 recovery on clinical outcomes.

KW - CD4

KW - HIV

KW - antiretroviral therapy

KW - immune response

KW - Humans

KW - Risk Factors

KW - Anti-HIV Agents/therapeutic use

KW - Logistic Models

KW - Male

KW - HIV Infections/drug therapy

KW - CD4 Lymphocyte Count/statistics & numerical data

KW - Treatment Failure

KW - Sex Factors

KW - Adult

KW - Female

KW - CD4-Positive T-Lymphocytes/drug effects

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