Pros and Cons of Early Antiretroviral Therapy Initiation
Patients showed the greatest BMD decrease during the first year of ART with spine BMD stabilizing after 1 year and hip BMD progressively decreasing over 2 years.
Patients with HIV who underwent immediate antiretroviral therapy (ART) saw significant decreases in bone mineral density (BMD) compared with patients who deferred their ART, according to recent research published in the Journal of Bone and Mineral Research.1
“In this diverse population of adults with HIV infection and near-normal CD4 counts, immediate initiation of ART resulted in significantly greater reductions in BMD at the spine and total hip compared with deferred ART,” Jennifer F. Hoy, MBBS, FRACP, from Monash University and The Alfred Hospital in Melbourne, Australia, and colleagues wrote in their study.
Dr Hoy and colleagues evaluated 399 patients with HIV in the START Bone Mineral Density substudy who underwent immediate (CD4 >500 cells/μL; n=195) or deferred (CD4 <350 cells/μL; n=204) ART. ART consisted of tenofovir and efavirenz in 95% of cases in the immediate ART and 18% in the deferred ART groups for follow up.
The researchers used percent change in BMD and dual energy X-ray absorptiometry (DXA) scans at baseline and follow-up to determine BMD loss at the lumbar spine and hip. Patients were mean 32 years old, 26% women, and 80% non-white with a median CD4 count of 642 cells/μL.
They found a –2.5% decrease in hip BMD in patients who began immediate ART compared with deferred ART (–1.0%) at mean 2.2-year follow-up (difference –1.5%, 95% CI, –2.2 to –0.8; P <.001), with a –1.9% decrease in spine BMD in patients who immediately initiated ART compared with a decrease of –0.4% in the deferred group over the same follow-up period (difference –1.6%; 95% CI, –2.2 to –1.0; P <.001).
Patients showed the greatest BMD decrease during the first year of ART; spine BMD stabilized after 1 year, while there was a progressive decrease in hip BMD over 2 years. BMD decreased in a similar fashion in both groups after 1 year. The researchers noted no ART, HIV, or clinical factor was associated with loss of BMD.
Summary & Clinical Applicability
“Given that ART use is lifelong in those with HIV, continued decline of BMD at rates greater than those observed in the general population, if that should be the case, may result in adverse outcomes in the aging HIV population,” Dr Hoy and colleagues wrote.
While the researchers noted the potential long-term effects of initiating ART immediately on BMD, they also noted that the clinical benefits of beginning ART early outweigh the decrease outcomes related to BMD.
“All key ART guidelines now recommend ART initiation at HIV diagnosis regardless of CD4 cell count because of the reduced risk of serious clinical outcomes relative to deferring ART,” Dr Hoy and colleagues wrote.
“Although the START Bone Mineral Density Substudy revealed an adverse effect of immediate ART, the overall benefits of ART for prevention of HIV transmission and adverse health outcomes prevail,” they added. “It will be important to understand the longer-term consequences of the observed reductions in BMD and whether these reductions continue or stabilize with longer therapy.”
Limitations & Disclosures
Researchers noted the short follow-up, low percentage of female participants, lack of applicability to specific drug effects, and lack of power to detect increased fracture risk as limitations in this study.
Hoy's institution received funding for her participation in Advisory Boards for Gilead Sciences, AbbVie, and ViiV Healthcare. Carr received funding from Gilead Sciences, MSD, Pfizer, and ViiV Healthcare, is a paid consultant for Mayne Pharma, Gilead Sciences, MSD, and ViiV Healthcare, received lecture and travel sponsorships from Bristol-Myers Squibb, Gilead Sciences, Janssen, MSD, and ViiV Healthcare, and is on the advisory board for Gilead Sciences, MSD, and ViiV Healthcare. Ensrud received travel support from Merck Sharp & Dohme. La Rosa received honoraria and salary from MSD and Janssen. Schwartz received a grant from Hologic Inc. The other researchers report no relevant financial disclosures.
- Hoy JF, Grund B, Roediger M, et al. 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. J Bone Miner Res. 2017. doi:10.1002/jbmr.3183 [Epub ahead of print]