Objectives: Initial antiretroviral therapy (ART) causes loss of bone mineral density (BMD) over the first 1–2 years. Whether this loss continues with longer therapy is unclear. We determined changes in bone and spine BMD over 5 years in adults receiving immediate or deferred initial ART. Methods: In the Strategic Timing of Antiretroviral Therapy (START) BMD substudy, ART-naïve adults with CD4 counts > 500 cells/μL were randomized to immediate or deferred ART. Deferred group participants not yet on ART were offered ART after May 2015. Mean per cent changes in total hip and lumbar spine BMD (measured annually by dual-energy X-ray absorptiometry) were compared between groups using longitudinal mixed models. Fracture rates were also compared between groups for all START participants. Results: Substudy participants (immediate group, n = 201; deferred group, n = 210; median age 32 years; 80% non-white; 24% female) were followed for a mean 4.5 years until December 2016. In the immediate group, > 96% used ART throughout. In the deferred group, 16%, 58% and 94% used ART at years 1, 3 and 5, respectively. BMD decreased more in the immediate group initially; groups had converged by year 3 at the spine and year 4 at the hip by intent-to-treat (ITT). BMD changes after year 1 were similar in the immediate group and in those off ART in the deferred group [mean difference: spine, 0.03% per year; 95% confidence interval (CI) −0.4, 0.4; P = 0.88; hip, −0.2% per year; 95% CI −0.7, 0.3; P = 0.37]. Fracture incidence did not differ significantly between groups (immediate group, 0.86/100 person-years versus deferred group, 0.85/100 person-years; hazard ratio 1.01; 95% CI 0.76, 1.35; P = 0.98). Conclusions: Significant ART-induced bone loss slowed after the first year of ART and became similar to that in untreated HIV infection.
Bibliographical noteFunding Information:
AC has received research funding from Bristol‐Myers Squibb, Gilead Sciences, and ViiV Healthcare; in‐kind research support from Novartis; conference travel sponsorships from Bristol‐Myers Squibb, Gilead Sciences, and ViiV Healthcare; and has served on advisory boards for Gilead Sciences, MSD and ViiV Healthcare. KE received travel support from Merck Sharp & Dohme for attendance at DMC meetings. AL received honoraria and salary from MSD and Janssen. AS has received a grant from Hologic Inc. JH's institution received funding for her participation in advisory boards for Gilead Sciences, AbbVie and ViiV Healthcare. BG, NWE, AVS, AA, SBF, JIB, VE, ALR, PWGM, SP and DW declare no conflict of interest. Conflicts of interest:
This work was supported by the National Institute of Allergy and Infectious Diseases (Grants U01‐AI068641, UM1‐AI120197 and 1U01‐AI136780), and National Institute of Arthritis and Musculoskeletal and Skin Diseases (Grant RO1 – AR060057‐01). The parent START study was 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 content is solely that of the authors and does not represent the views of the National Institutes of Health, nor those of AbbVie, Bristol‐Myers Squibb, Gilead Sciences, GlaxoSmithKline/ViiV Healthcare, Janssen Scientific Affairs, or Merck. Financial disclosure:
- antiretroviral therapy
- bone mineral density
- clinical trial