Immediate Initiation of Antiretroviral Therapy for HIV Infection Accelerates Bone Loss Relative to Deferring Therapy: Findings from the START Bone Mineral Density Substudy, a Randomized Trial

Jennifer F. Hoy, Birgit Grund, Mollie Roediger, Ann V. Schwartz, John Shepherd, Anchalee Avihingsanon, Sharlaa Badal-Faesen, Stephane de Wit, Simone Jacoby, Alberto La Rosa, Sanjay Pujari, Mauro Schechter, David White, Nicole Wyman Engen, Kristine Ensrud, Peer D. Aagaard, Andrew Carr, for the INSIGHT START Bone Mineral Density Substudy Group

Research output: Contribution to journalArticle

7 Citations (Scopus)

Abstract

Both HIV infection and antiretroviral therapy (ART) are associated with lower bone mineral density (BMD) and increased fracture risk. Because the relative contributions of ART and untreated HIV to BMD loss are unclear, it is important to quantify the effect of ART on bone. We compared the effect of early ART initiation (CD4 >500 cells/μL) with deferred ART on change in BMD in the START Bone Mineral Density substudy, a randomized trial evaluating the effect of immediate ART initiation versus deferring ART (to CD4 <350 cells/μL). BMD was measured annually at the lumbar spine and hip by dual-energy X-ray absorptiometry (DXA). Percent change in BMD by treatment assignment (intent-to-treat analysis) was estimated using longitudinal mixed models and linear regression. Baseline and follow-up DXA scans were available for 399 (195 immediate, 204 deferred) participants (median age 32 years, 80% non-white, 26% women, median CD4 count 642 cells/μL). ART (most commonly including tenofovir and efavirenz) was used for 95% and 18% of follow-up in the immediate and deferred ART groups, respectively. Through 2.2 years mean follow-up, immediate ART resulted in greater BMD declines than deferred ART at the hip (–2.5% versus –1.0%; difference –1.5%, 95% confidence interval [CI] –2.2 to –0.8, p < 0.001) and spine (–1.9% versus –0.4%; difference –1.6%, 95% CI –2.2 to –1.0, p < 0.001). BMD declines were greatest in the first year of ART. In the immediate ART group, spine BMD stabilized after year 1, whereas hip BMD declined progressively over 2 years. After year 1, BMD changes were similar in the immediate and deferred groups. No clinical, HIV-related, or ART characteristic predicted greater BMD loss in either group. All HIV treatment guidelines now recommend ART initiation at HIV diagnosis because of the reduced risk of serious clinical outcomes. Better understanding of the longer-term consequences of the observed reductions in BMD is needed. Clinical Trials Registration: NCT00867048.

Original languageEnglish (US)
Pages (from-to)1945-1955
Number of pages11
JournalJournal of Bone and Mineral Research
Volume32
Issue number9
DOIs
StatePublished - Sep 1 2017

Fingerprint

Bone Density
HIV Infections
Bone and Bones
Therapeutics
HIV
Spine
Tenofovir
efavirenz
Photon Absorptiometry
Group Psychotherapy
Hip
Pelvic Bones
Confidence Intervals
CD4 Lymphocyte Count
Secondary Prevention
Linear Models
Clinical Trials
Guidelines

Keywords

  • ANTIRETROVIRAL THERAPY
  • BONE MINERAL DENSITY
  • CLINICAL TRIALS
  • DXA
  • HIV

Cite this

Immediate Initiation of Antiretroviral Therapy for HIV Infection Accelerates Bone Loss Relative to Deferring Therapy : Findings from the START Bone Mineral Density Substudy, a Randomized Trial. / Hoy, Jennifer F.; Grund, Birgit; Roediger, Mollie; Schwartz, Ann V.; Shepherd, John; Avihingsanon, Anchalee; Badal-Faesen, Sharlaa; de Wit, Stephane; Jacoby, Simone; La Rosa, Alberto; Pujari, Sanjay; Schechter, Mauro; White, David; Engen, Nicole Wyman; Ensrud, Kristine; Aagaard, Peer D.; Carr, Andrew; for the INSIGHT START Bone Mineral Density Substudy Group.

In: Journal of Bone and Mineral Research, Vol. 32, No. 9, 01.09.2017, p. 1945-1955.

Research output: Contribution to journalArticle

Hoy, JF, Grund, B, Roediger, M, Schwartz, AV, Shepherd, J, Avihingsanon, A, Badal-Faesen, S, de Wit, S, Jacoby, S, La Rosa, A, Pujari, S, Schechter, M, White, D, Engen, NW, Ensrud, K, Aagaard, PD, Carr, A & for the INSIGHT START Bone Mineral Density Substudy Group 2017, 'Immediate Initiation of Antiretroviral Therapy for HIV Infection Accelerates Bone Loss Relative to Deferring Therapy: Findings from the START Bone Mineral Density Substudy, a Randomized Trial', Journal of Bone and Mineral Research, vol. 32, no. 9, pp. 1945-1955. https://doi.org/10.1002/jbmr.3183
Hoy, Jennifer F. ; Grund, Birgit ; Roediger, Mollie ; Schwartz, Ann V. ; Shepherd, John ; Avihingsanon, Anchalee ; Badal-Faesen, Sharlaa ; de Wit, Stephane ; Jacoby, Simone ; La Rosa, Alberto ; Pujari, Sanjay ; Schechter, Mauro ; White, David ; Engen, Nicole Wyman ; Ensrud, Kristine ; Aagaard, Peer D. ; Carr, Andrew ; for the INSIGHT START Bone Mineral Density Substudy Group. / Immediate Initiation of Antiretroviral Therapy for HIV Infection Accelerates Bone Loss Relative to Deferring Therapy : Findings from the START Bone Mineral Density Substudy, a Randomized Trial. In: Journal of Bone and Mineral Research. 2017 ; Vol. 32, No. 9. pp. 1945-1955.
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abstract = "Both HIV infection and antiretroviral therapy (ART) are associated with lower bone mineral density (BMD) and increased fracture risk. Because the relative contributions of ART and untreated HIV to BMD loss are unclear, it is important to quantify the effect of ART on bone. We compared the effect of early ART initiation (CD4 >500 cells/μL) with deferred ART on change in BMD in the START Bone Mineral Density substudy, a randomized trial evaluating the effect of immediate ART initiation versus deferring ART (to CD4 <350 cells/μL). BMD was measured annually at the lumbar spine and hip by dual-energy X-ray absorptiometry (DXA). Percent change in BMD by treatment assignment (intent-to-treat analysis) was estimated using longitudinal mixed models and linear regression. Baseline and follow-up DXA scans were available for 399 (195 immediate, 204 deferred) participants (median age 32 years, 80{\%} non-white, 26{\%} women, median CD4 count 642 cells/μL). ART (most commonly including tenofovir and efavirenz) was used for 95{\%} and 18{\%} of follow-up in the immediate and deferred ART groups, respectively. Through 2.2 years mean follow-up, immediate ART resulted in greater BMD declines than deferred ART at the hip (–2.5{\%} versus –1.0{\%}; difference –1.5{\%}, 95{\%} confidence interval [CI] –2.2 to –0.8, p < 0.001) and spine (–1.9{\%} versus –0.4{\%}; difference –1.6{\%}, 95{\%} CI –2.2 to –1.0, p < 0.001). BMD declines were greatest in the first year of ART. In the immediate ART group, spine BMD stabilized after year 1, whereas hip BMD declined progressively over 2 years. After year 1, BMD changes were similar in the immediate and deferred groups. No clinical, HIV-related, or ART characteristic predicted greater BMD loss in either group. All HIV treatment guidelines now recommend ART initiation at HIV diagnosis because of the reduced risk of serious clinical outcomes. Better understanding of the longer-term consequences of the observed reductions in BMD is needed. Clinical Trials Registration: NCT00867048.",
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N2 - Both HIV infection and antiretroviral therapy (ART) are associated with lower bone mineral density (BMD) and increased fracture risk. Because the relative contributions of ART and untreated HIV to BMD loss are unclear, it is important to quantify the effect of ART on bone. We compared the effect of early ART initiation (CD4 >500 cells/μL) with deferred ART on change in BMD in the START Bone Mineral Density substudy, a randomized trial evaluating the effect of immediate ART initiation versus deferring ART (to CD4 <350 cells/μL). BMD was measured annually at the lumbar spine and hip by dual-energy X-ray absorptiometry (DXA). Percent change in BMD by treatment assignment (intent-to-treat analysis) was estimated using longitudinal mixed models and linear regression. Baseline and follow-up DXA scans were available for 399 (195 immediate, 204 deferred) participants (median age 32 years, 80% non-white, 26% women, median CD4 count 642 cells/μL). ART (most commonly including tenofovir and efavirenz) was used for 95% and 18% of follow-up in the immediate and deferred ART groups, respectively. Through 2.2 years mean follow-up, immediate ART resulted in greater BMD declines than deferred ART at the hip (–2.5% versus –1.0%; difference –1.5%, 95% confidence interval [CI] –2.2 to –0.8, p < 0.001) and spine (–1.9% versus –0.4%; difference –1.6%, 95% CI –2.2 to –1.0, p < 0.001). BMD declines were greatest in the first year of ART. In the immediate ART group, spine BMD stabilized after year 1, whereas hip BMD declined progressively over 2 years. After year 1, BMD changes were similar in the immediate and deferred groups. No clinical, HIV-related, or ART characteristic predicted greater BMD loss in either group. All HIV treatment guidelines now recommend ART initiation at HIV diagnosis because of the reduced risk of serious clinical outcomes. Better understanding of the longer-term consequences of the observed reductions in BMD is needed. Clinical Trials Registration: NCT00867048.

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