The benefit of immediate antiretroviral therapy (ART) at CD4 >500 cells/ìL was established in the Strategic Timing of Antiretroviral Treatment (START) study. The benefits and risks of immediate ART in participants with low pre-treatment viremia, including virologic suppressors, was further assessed.
Randomized prospective international study
START participants with enrollment viremia <3000c/mL were included. We compared clinical outcomes (grade 4 adverse events, hospitalisations or death), plasma viremia, CD4 counts and changes in biomarkers in immediate versus deferred ART groups.
Participants (N=1134 including 93 with viremia ≤50 c/mL) had a median age of 37 years, 40% were female and median CD4 was 713 cells/µL. 97% 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 vs 61 patients in immediate and deferred arms (hazard ratio 1.10 95% CI 0.77 1.56). The CD4 count difference was 125 cells/µL at 12 and 235 cells/µL at 36 months higher in the immediate vs deferred groups. D-dimer and VCAM levels decreased, and CRP 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.
START participants with low enrollment viremia experienced higher CD4 counts, greater proportion with suppressed viremia, and decreases in D-dimer levels upon immediate ART despite the lack of difference in serious clinical outcomes. These data support immediate ART in people with low viremia although equipose remains for suppressors.
2Weill Cornell Medicine, USA,
3Leicester Royal Infirmary, Leicester, UK,
4University Vienna General Hospital, Austria,
5CICAL and Hospital Italiano de Buenos Aires Argentina,
6Faculty of Medicine, University of New South Wales, Australia,
7Kirby Institute, University of New South Wales, Australia
Correspondence to Prof Matthew Law, The Kirby Institute, Level 6, Wallace Wurth Building, UNSW Sydney, NSW 2052, Australia. E-mail address: email@example.com, telephone number: +61 2 9385 0900, fax number: +61 2 9385 0920
* See N Engl J Med 2015; 373:795-807 for the complete list of START investigators.
Conflicts of Interest and Source of Funding: 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. ML 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, AP reported receiving funds from Gilead Sciences as a partial contribution towards the costs of attending the CROI conference in Boston MA in 2018. For the remaining authors no relevant conflict of interest was declared.