The Rate of Bone Loss Slows After 1–2 Years of Initial Antiretroviral Therapy

Final Results of the Strategic Timing of Antiretroviral Therapy (START) Bone Mineral Density Substudy

A Carr; B Grund; AV Schwartz; A Avihingsanon; S Badal-Faesen; JI Bernadino; V Estrada; A La Rosa; PWG Mallon; S Pujari; D White; N Wyman Engen; K Ensrud; JF Hoy


HIV Medicine. 2020;21(1):64-70. 

In This Article


These final data from the START BMD substudy confirm that initial ART significantly accelerates BMD loss over the first 1–2 years in young adults. With up to 5 years of follow-up, there was evidence for ongoing BMD loss in both groups, but the between-group difference in later years was modest and not significant.

Our data provide reassurance that the steep rate of BMD loss in the first year of ART is ameliorated in subsequent years, as observed in other cohorts.[15–17] Indeed, after year 1, the rate of loss in the immediate ART group was similar to that in patients who remained ART naïve in the deferred group. This finding supports similar data comparing adults on stable ART and matched HIV-negative controls.[15] However, the rate of decline after year 1 remained greater than might be expected in a population of this age.[18] The normal rate of decline in BMD in later years is influenced by race/ethnicity and age.[19,20] Our participants were racially diverse, so a comparison with a cohort such as National Health and Nutrition Examination Survey III may not be appropriate. Longitudinal data from a Canadian study suggest that there is virtually no loss of BMD at either hip or spine until after the age of 40 years.[18]

There was no consistent signal for CD4 count, CD8 count or CD4:CD8 ratio as a predictor of greater bone loss at both the hip or the spine. Our results are in agreement with those of others who reported that a higher pre-ART viral load predicted greater bone loss with initiation of ART.[2,17] Our study is also in agreement with another randomized trial of ART in which a lower CD4 count did not predict greater bone loss on initiation of ART,[4] in contrast to other studies.[17] The finding that higher CD8 counts were associated with greater bone loss in those initiating ART is novel and not previously reported. The finding that none of the traditional risk factors for bone loss predicted change in BMD may have been attributable to the young age of our study population.

Our analysis has limitations. Most participants in the deferred group had initiated ART by year 4. Therefore, the ITT comparison between the immediate and deferred groups does not accurately quantify the effect of ART versus untreated HIV infection in the later years, while comparison of the immediate group versus patients with untreated HIV infection in the deferred group is not protected by randomization. However, given that immediate ART is now standard-of-care, it is highly unlikely that another study will ever evaluate the long-term effects of ART relative to no ART. Most ART regimens contained TDF, which is a well-known cause of BMD loss; TDF remains a common backbone, in part because of its preferred status within the World Health Organization (WHO) guidelines.[21]

In summary, bone loss with initial ART slowed after the first year of ART, and the rates of change in BMD after the first year were similar with and without ART. In this relatively young population, ART-related BMD loss did not translate into a greater incidence of fractures.