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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

Boatman, Jeffrey A., PhDa; Baker, Jason V., MS, MDa,b; Emery, Sean, PhDc; Furrer, Hansjakob, MDd; Mushatt, David M., MPH&TM, MDe; Sedláček, Dalibor, MD, PhDf; Lundgren, Jens D., MDg; Neaton, James D., PhDa for the INSIGHT START Study Group

JAIDS Journal of Acquired Immune Deficiency Syndromes: May 1, 2019 - Volume 81 - Issue 1 - p 10–17
doi: 10.1097/QAI.0000000000001967

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/mm3.

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/mm3 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/mm3; P = 0.004), higher baseline CD8+ cell counts (OR, 1.05 per 100 more cells/mm3; 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.

aUniversity of Minnesota, Minneapolis, MN;

bHennepin Healthcare Research Institute, Minneapolis, MN;

cUniversity of New South Wales, Sydney, Australia;

dBern University Hospital, University of Bern, Bern, Switzerland;

eTulane University, New Orleans, LA;

fCharles University Hospital, Plzen, Czech Republic; and

gUniversity of Copenhagen, Denmark.

Correspondence to: Jeffrey A. Boatman, PhD, Division of Biostatistics, School of Public Health, University of Minnesota, A460 Mayo Building, MMC 303, 420 Delaware Street SE, Minneapolis, MN 55455 (e-mail:

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.

The authors have no conflicts of interest to disclose.

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Received September 10, 2018

Accepted December 20, 2018

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