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  Conference on Retroviruses
and Opportunistic Infections (CROI)
Boston, Massachusetts
March 4-7, 2018
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Combined Effects of Bisphosphonates and TDF→TAF Switch in HIV+ Adults With Low BMD
  Bisphosphonates Boost TDF-to-TAF Impact on Spine BMD But Not Hip BMD
25th Conference on Retroviruses and Opportunistic Infections (CROI), March 4-7, 2018, Boston
Mark Mascolini
Taking bisphosphonates when switching from tenofovir disoproxil fumarate (TDF) to tenofovir alafenamide (TAF) further improved bone mineral density (BMD) gains in the spine, but not the hip [1]. Reasons for the spine/hip difference in this 214-person analysis could include a more blunted hip response to any intervention in people with or without HIV.
When people switch from TDF to TAF, BMD typically improves 2% to 3% over 2 to 3 years, noted Todd Brown (Johns Hopkins University) and an international team who conducted this analysis. Bisphosphonates boost BMD in people with HIV 8% at the lumbar spine and 4% at the total hip through 2 years [2]. To learn whether bisphosphonates enhance BMD surges attained in a TDF-to-TAF switch, these researchers retrospectively combined and analyzed data from two 144-week phase 3 trials in which virologically suppressed people swapped a TDF regimen for TAF coformulated with elvitegravir, cobicistat, and emtricitabine (NCT01815736 and NCT01818596).
The analysis focused on people in whom baseline DXA scans showed clinically significant low BMD, defined as a T score at or below 2.0 at the lumbar spine, femoral neck, or total hip. The researchers used linear regression analysis to assess the added impact of bisphosphonates independent of age, race, sex, body mass index, current smoking, and initial BMD.
Among 1117 adults enrolled in the two trials, 214 (19%) had low initial BMD, including 93 (43%) with osteoporosis. Of those 214 people, 30 (14%) used bisphosphonates for a median 754 days and 184 did not. Compared with people who did not take bisphosphonates, those who did were older (median 50 versus 45) and more likely to be women (33% versus 12%), to have lower spine and hip BMD, to have osteoporosis (47% versus 31%), to smoke (40% versus 23%), and to have a higher 10-year hip fracture probability (FRAX 2.19% versus 0.82%). The bisphosphonate group had a lower proportion of blacks (7% versus 17%).
After 144 weeks both bisphosphonate users and nonusers had significant gains in hip and spine BMD (P < 0.001). Spine BMD rose significantly more in bisphosphonate users than nonusers (median 5.1% versus 2.6%, P = 0.002). But bisphosphonate users did not gain significantly more hip BMD (median 4.0% versus 2.3%, P = 0.29). Both users and nonusers had significant gains from baseline hip and spine T scores. But compared with nonusers, bisphosphonate users significantly boosted their spine T score (median 0.40 versus 0.20, P = 0.002) but not their hip T score (median 0.25 versus 0.14, P = 0.15). Adjusted regression analysis confirmed a significantly greater change in spine BMD and T score at week 144 in bisphosphonate users than nonusers. But change in hip BMD and T score did not differ between users and nonusers in these analyses.
The researchers proposed that the impact of adding bisphosphonates to switching from TDF through 144 weeks "may not be additive, particularly at the hip." They suggested that a trial could compare a sequential strategy of a TDF switch followed by bisphosphonates versus the combined strategy assessed here. But such a trial becomes increasingly difficult as more and more TDF takers switch to TAF on their own.
1. Brown TT, Yin MT, Gupta SK, et al. Combined effects of bisphosphonates and TDF --> TAF switch in HIV+ adults with low BMD. 25th Conference on Retroviruses and Opportunistic Infections (CROI). March 4-7, 2018. Boston. Abstract 724.
2. Pinzone MR, Moreno S, Cacopardo B, Nunnari G. Is there enough evidence to use bisphosphonates in HIV-infected patients? A systematic review and meta-analysis. AIDS Rev. 2014;16:213-222.
Combined Effects of Bisphosphonates and TDF→TAF Switch in HIV+ Adults With Low BMD
Reported by Jules Levin CROI 2018 March 4-7 Boston MA
Todd Brown,1 Michael T. Yin,2 Samir K. Gupta,3 William R. Short,4 Melanie Thompson,5 Daniel Podzamczer,6 Giovanni Di Perri,7 Cheryl McDonald,8 Matthias Cavassini,9 Pablo Tebas,4 Ya-Pei Liu,10 Scott McCallister,10 Andrew Cheng,10 Moupali Das10 1Johns Hopkins University, Baltimore, MD; 2Columbia University Medical Center, New York, NY; 3Indiana University School of Medicine, Indianapolis, IN; 4Perelman School of Medicine, University of Pennsylvania, Philadelphia; 5AIDS Research Consortium of Atlanta, GA; 6Hospital Universitari de Bellvitge, Barcelona, Spain; 7Comprensorio Ospedaliero Amedeo di Savoia-Birago di Vische, Turin, Italy; 8Tarrant County Infectious Disease Associates, Fort Worth, TX; 9Centre Hospitalier Universitaire Vaudois, Lausanne, Switzerland; 10Gilead Sciences, Inc., Foster City, CA