Young US men enrolled in an open-label tenofovir/emtricitabine (TDF/FTC) preexposure prophylaxis (PrEP) protocol regained bone mineral density (BMD) lost while on PrEP during the 48 weeks after they stopped . But bone density Z scores from before PrEP to 48 weeks after stopping PrEP suggested TDF stymied bone growth during this critical lifetime phase of bone formation. Z scores compare BMD with a population norm figured by age, gender, and race.
Declining BMD is a well-appreciated side effect of TDF and a concern for people who may use TDF/FTC PrEP over an extended period. That concern is pronounced for young people, who are reaching peak bone mass in their teens and 20s. Adolescent Trials Network (ATN) protocol 110 offered an opportunity to measure changes in BMD during and after months of TDF/FTC PrEP in people whose bones should be growing.
ATN 110 recruited 200 HIV-negative 18- to 22-year-old US men with a self-reported high risk of HIV infection in the past 6 months . All men were invited to begin daily TDF/FTC PrEP. Follow-up continued for 48 weeks. Participants had DXA scans of the hip, spine, and whole body at baseline and weeks 24 and 48.
Median age stood at 20 years (range 18 to 22), 46.5% of participants were African American, and 26.5% Latino; 79% of men identified themselves as gay and 14% as bisexual. Almost all men, 98.3%, decided to start PrEP immediately. Z scores showed below-normal BMD in the spine, hip, and total body even before PrEP began. Through 48 weeks, BMD dropped about 1% at the hip and about 0.6% in the whole body (P < 0.001) but not in the spine . Percent changes in spine and hip BMD at week 48 correlated with tenofovir diphosphate levels in blood cells.
The new analysis tracked BMD changes after men stopped TDF/FTC PrEP. The study focused on men who lost BMD or failed to gain BMD during 48 weeks of PrEP. They had repeat DXA scans 24 and 48 weeks after stopping PrEP. Of 135 men who had DXA scans after 48 weeks of PrEP, 102 (76%) met age-related BMD or kidney criteria for the extension phase. The researchers excluded 6 men who picked up HIV and separately analyzed 16 men who continued PrEP through their primary providers. The 6 new infections yielded a hefty HIV incidence of 7.2 per 100 person-years.
Excluding men lost to follow-up left 72 men who had at least one DXA during the 48 weeks after stopping PrEP. BMD drops through 48 weeks of PrEP averaged -0.2% in the spine (not significant), -1.4% in the hip (P = 0.002), and -0.6% in the whole body (P = 0.03). In the 48 weeks after PrEP stopped, BMD rose significantly at each of those sites: +1.1% in the spine (P = 0.003), +1.0% in the hip (P = 0.04), and +0.6% in the whole body (P = 0.01).
Net changes in BMD from before PrEP through 48 weeks after PrEP stopped were not statistically significant: +0.6% in the spine, -0.5% in the hip, and -0.2% in the whole body. But over that period, BMD fell significantly when figured as Z scores reflecting population norms in the spine (-0.18%, P < 0.0001) and whole body (-0.08%, P = 0.03) but not the hip (-0.05, P = 0.22).
The ATN investigators believe the Z-score comparison suggests “some impairment in bone growth” in these young men. They think their results “highlight the continuing need for strategies to mitigate bone loss in at-risk young MSM during a period when they should be acquiring bone.” Slowed bone growth is particularly worrisome in these study participants, who had below-normal bone density before starting PrEP.
By Mark Mascolini
1. Mulligan K, Hosek S, Kapogiannis BG, et al. Changes in bone mass after discontinuation of pre-exposure prophylaxis (PrEP) with tenofovir disoproxil fumarate/emtricitabine in young men who have sex with men who lost bone while using PrEP: extension phase results of Adolescent Trials Network protocol 110. 18th International Workshop on Comorbidities and Adverse Drug Reactions in HIV, September 12-13, 2016, New York. Abstract 001.
2. Hosek S, Rudy B, Landovitz R, et al. An HIV pre-exposure prophylaxis (PrEP) demonstration project and safety study for young MSM ages 18-22 in the United States (ATN 110). J Acquir Immune Defic Syndr, In press.
3. Mulligan K, Rutledge B, Kapogiannis B, et al. Bone changes in young men ages 18-22 enrolled in a pre-exposure prophylaxis (PrEP) demonstration project using tenofovir disoproxil fumarate/emtricitabine (TDF/FTC). 17th International Workshop on Co-morbidities and Adverse Drug Reactions in HIV, October 21-24, 2015, Barcelona. http://www.hivguidelines.org/wp-content/uploads/2015/12/Bill.Kapogiannis.AdolescentForum.11.18.15.pdf (Bone mineral density findings appear halfway through the linked file.)