A Carr1, B Grund2, A V Schwartz3, A Avihingsanon4, S Badal-Faesen5, J I Bernadino6, V Estrada7, A La Rosa8, Pwg Mallon9, S Pujari10, D White11, N Wyman Engen2, K Ensrud2,12, J F Hoy13. 1. St Vincent's Hospital, Sydney, Australia. 2. University of Minnesota, Minneapolis, MN, USA. 3. University of California San Francisco, San Francisco, CA, USA. 4. Thai Red Cross AIDS Research Center and Faculty of Medicine, Chulalongkorn University, Bangkok, Thailand. 5. Clinical HIV Research Unit, University of Witwatersrand, Johannesburg, South Africa. 6. Hospital Universitario La Paz, IdiPAZ, Madrid, Spain. 7. Hospital Clinico San Carlos, Madrid, Spain. 8. Asociacion Civil Impacta Salud y Educacion, Lima, Peru. 9. University College Dublin, Dublin, Ireland. 10. Institute of Infectious Diseases, Pune, India. 11. Heart of England NHS Foundation Trust, Birmingham, UK. 12. Minneapolis VA Health Care System, Minneapolis, MN, USA. 13. The Alfred Hospital, Monash University, Melbourne, VIC, Australia.
Abstract
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.
RCT Entities:
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.
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