Background:
Bone mineral density (BMD) loss has been a concern for HIV pre-exposure prophylaxis (PrEP) containing tenofovir disoproxil fumarate (TDF). Long-acting cabotegravir (CAB-LA) was superior to TDF/emtricitabine (FTC) for HIV prevention in two clinical trials, but the relative bone safety of these regimens is unknown.
Methods:
HPTN 083 conducted a bone safety sub-study to compare BMD changes over 105 weeks with CAB-LA and TDF/FTC in cisgender men who have sex with men (MSM) and transgender women (TGW) at risk for HIV infection from 22 international sites. BMD was measured at the lumbar spine (LS), femoral neck, and total hip by dual-energy x-ray absorptiometry (DXA) at baseline, 57 weeks, and 105 weeks. Percentage BMD change at each anatomic site was compared between the two randomized arms by two-sample, independent t-tests in those who received at least 10 bi-monthly injections over 18 months from enrollment (n=254).
Results:
At baseline the median (Q1, Q3) age was 27 (23, 35) years, 9.4% TGW, and 47.2% white. The proportion of those with low BMD at baseline (Z-score at any anatomic site £ -2.0) was 15%. At the LS, the median percentage change in BMD was 0.82% in the CAB-LA arm and -0.82% in the TDF/FTC arm (between arm difference (95% confidence interval [CI] –1.6% [-2.4, -0.87], p< 0.01) at 57 weeks (n=248). This difference persisted at 105 weeks (n=203) with a between-arm difference in percentage BMD change of -2.3% (95%CI: -3.4, -1.1%; p< 0.01). Similar results were observed at both the femoral neck and total hip (Figure).
Conclusions:
Among MSM and TGW receiving CAB-LA versus TDF/FTC HIV PrEP, bone mineral density trajectories over two years were different, with BMD gain in the CAB-LA arm and BMD loss in the TDF/FTC arm. For individuals with low BMD or other fracture risk factors, CAB-LA PrEP may confer benefits related to bone health compared to TDF-containing PrEP.
Percent BMD Difference From Enrollment by Study Arm 