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ART in HIV-Positive Persons With Low Pretreatment Viremia

Results From the START Trial

Sereti, Irini MD, MHSca; Gulick, Roy M. MD, MPHb; Krishnan, Sonya MDa; Migueles, Stephen A. MDc; Palfreeman, Adrian FRCP, FRCPId; Touzeau-Römer, Veronique MDe; Belloso, Waldo H. MDf; Emery, Sean MA, MSc, PhDg; Law, Matthew G. MA, MSc, PhDh for the INSIGHT START Study Group

JAIDS Journal of Acquired Immune Deficiency Syndromes: August 1, 2019 - Volume 81 - Issue 4 - p 456–462
doi: 10.1097/QAI.0000000000002052
Clinical Science

Background: The benefit of immediate antiretroviral therapy (ART) at CD4 >500 cells/μL was established in the Strategic Timing of Antiretroviral Treatment (START) study. The benefits and risks of immediate ART in participants with low pretreatment viremia, including virologic suppressors, were further assessed.

Setting: Randomized prospective international study.

Methods: START participants with enrollment viremia <3000 c/mL were included. We compared clinical outcomes (grade 4 adverse events, hospitalizations, or death), plasma viremia, CD4 counts, and changes in biomarkers in immediate versus deferred ART groups.

Results: Participants (N = 1134 including 93 with viremia ≤50 c/mL) had a median age of 37 years, 40% were women, and median CD4 was 713 cells/µL. Ninety-seven percent in the immediate and 29% in the deferred arm initiated ART at a median of 6 and 699 days, respectively. Clinical outcomes were experienced in 64 versus 61 patients in immediate and deferred arms (hazard ratio 1.10, 95% confidence interval: 0.77 to 1.56). The CD4 count difference was 125 cells/µL at 12 and 235 cells/µL at 36 months higher in the immediate versus deferred groups. D-dimer and VCAM levels decreased, and C-reactive protein increased, in the immediate arm at month 8. No significant changes in CD4 counts or biomarkers were observed in persons who maintained spontaneous virologic suppression.

Conclusions: START participants with low enrollment viremia experienced higher CD4 counts, greater proportion with suppressed viremia, and decreases in D-dimer levels on immediate ART despite the lack of difference in serious clinical outcomes. These data support immediate ART in people with low viremia, although equipoise remains for suppressors.

aHIV Pathogenesis Section, NIAID/NIH, Bethesda, MD

bInfectious Diseases, Weill Cornell Medicine, Weill Cornell Medical College, Cornell University, New York, NY

cHIV-Specific Immunity Section, NIAID/NIH, Bethesda, MD;

dDepartment of Genitourinary Medicine, Leicester Royal Infirmary, Leicester, United Kingdom;

eDepartment of Immunodermatology and Infectious Skin Diseases, University Vienna General Hospital, Vienna, Austria;

fCICAL and Infectious Diseases Section, Internal Medicine Service, Hospital Italiano de Buenos Aires Argentina, Buenos Aires, Argentina;

gFaculty of Medicine, University of New South Wales, Sydney, Australia; and

hFaculty of Medicine, Kirby Institute, University of New South Wales, Sydney, Australia.

Correspondence to: Matthew G. Law, MA, MSc, PhD, The Kirby Institute, Level 6, Wallace Wurth Building, UNSW Sydney, NSW 2052, Australia (e-mail:

Supported by NIH Grants UM1-AI068641 and UM1-AI120197, the intramural research program of NIAID/NIH, the Cornell CTSC (UL1-RR024996), 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 (United States), Agence Nationale de Recherches sur le SIDA et les Hipatites Virales (France), National Health and Medical Research Council (Australia), National Research Foundation (Denmark), Bundes ministerium for Bildung und Forschung (Germany), European AIDS Treatment Network, Medical Research Council (United Kingdom), National Institute for Health Research, National Health Service (United Kingdom), and the 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.

Presented in part at the Conference on Retroviruses and Opportunistic Infections (CROI); February 2017; Seattle, WA.

M.G.L. reported unrestricted grants from Boehringer Ingelhiem, Gilead Sciences, Merck Sharp & Dohme, Bristol-Myers Squibb, Janssen-Cilag, ViiV Healthcare, and consultancy and presentation fees from Gilead Sciences, A.P. reported receiving funds from Gilead Sciences as a partial contribution toward the costs of attending the CROI conference in Boston, MA, in 2018. The remaining authors have no conflicts of interest to disclose.

Supplemental digital content is available for this article. Direct URL citations appear in the printed text and are provided in the HTML and PDF versions of this article on the journal's Web site (

See N Engl J Med 2015; 373:795-807 for the complete list of START investigators.

Received December 06, 2018

Accepted March 07, 2019

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