Starting earlier on ARVs accelerates decline in bone mineral density

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Those who start antiretroviral (ARV) treatment for HIV as soon after diagnosis as possible experience a greater decline in bone mineral density compared with those assigned in a study to delay going on ARVs until their immune system deteriorates somewhat.

Publishing their findings, scientists from the START Bone Mineral Density Sub-study randomised 399 HIV-positive individuals with a CD4 count greater than 500 to start ARVs immediately or wait until their CD4s dropped below 350.

The randomized controlled START study definitively established that there is a net health benefit to starting ARVs early in the course of infection rather than delaying. The large study’s robust findings led to global recommendations that individuals begin HIV treatment as soon as possible after diagnosis.

In this newly published sub-study, the researchers followed the participants, 195 of whom were in the immediate treatment arm and 204 of whom were in the deferred treatment arm, for an average of 2.2 years. They measured the participants’ bone mineral density every 12 months at the lumbar spine and hip through dual-energy X-ray absorptiometry (DXA).

The participants were 32 years old on average and had an average CD4 count of 642 – 80% were non-white, 26% were women.

Those in the immediate treatment group used ARVs for 95% of the follow-up period while those in the deferred treatment arm used them for 18% of the follow-up period. The most common ARVs used in the participants’ treatment regimens were the two components of Truvada (tenofovir disoproxil fumarate/emtricitabine).

During the study’s follow-up, bone mineral density at the hip declined by 2.5% in the immediate treatment arm and 1% in the deferred treatment arm, for a difference of 1.5%. Bone mineral density at the spine declined 1.9% in the immediate treatment arm and 0.4% in the deferred treatment arm, for a difference of 1.6% (the figures were rounded).

Overall declines in bone mineral density were greatest during participants’ first year on ARVs. In the immediate treatment group, spine bone mineral density stabilised after the first year of follow-up, while hip bone mineral density declined progressively over two years of follow-up. After the first year of follow-up, overall changes in bone mineral density were similar between the two study arms.

The researchers could not identify any clinical or HIV-related factors associated with greater bone mineral density loss, nor could they pinpoint any factors to do with specific ARV regimens themselves linked to bone loss.

“Better understanding of the longer-term consequences of the observed reductions in (bone mineral density) is needed,” the study authors concluded.

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.

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

Poz report
Journal of Bone and Mineral Research abstract

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