ABSTRACT
Background: The mechanism of bone loss in antiretroviral-treated HIV-positive patients is poorly understood. Plasma bone turnover markers(BTMs) suggest uncoupling of bone resorption and formation by a treatment effect on bone cells. Switching away from TDF to TAF-containing regimens has been associated with bone mineral density(BMD) gains measured by dual-energy X-ray absorptiometry (DXA). One explanation is reversal of ongoing subclinical bone loss in the TDF to TAF switchers. Quantitative imaging with 18F-PET/CT allows assessment of regional bone formation at specific skeletal sites and can help differentiate if BMD changes are associated with increased bone formation or reduced bone loss. Methods: PETRAM, an open-label, randomised study conducted at a single UK site, enrolled non-osteoporotic virologically suppressed HIV-positive males, on >24 weeks rilpivirine/emtricitabine/TDF (RPV/FTC/TDF). They were randomised 1:1 to remain on RPV/FTC/TDF or switch to RPV/FTC/TAF. The protocol specified scanning by DXA (to measure BMD) and 18F-PET/CT at several regions of interest-with primary focus on the lumbar spine (LS) and total hip (TH)-at baseline, 24 weeks, and 48 weeks. However, the timing of scans was disrupted, and in some cases considerably delayed, by COVID-19. The primary analysis was therefore based on change between the baseline and final scans, adjusting for the interval between them. Regions of interest were drawn on the PET/CT images and the standardised uptake value (SUV) measured. A sample of 30 (15 per arm) was estimated to provide 90% power to detect a difference in change of 25% in SUV between the randomised groups. Results: 32 males, median age 51 years, 76% White ethnicity, median duration RPV/FTC/TDF of 49 months, BMI 25.5 kg/m2 were enrolled;27(16 TAF:11 TDF) were included in the final analysis. The interval between baseline and final scans ranged between 23-103 weeks (median 55 weeks). There was no significant difference in change in SUV(18F-PET/CT) at the LS or TH between the TAF and TDF arms (Table);there was a trend towards improved LS BMD, but not TH BMD, in the TAF arm. Conclusion: As measured by 18F-PET/CT, regional bone formation at the hip or LS in patients replacing TDF with TAF in their ART combination did not differ, and contrary to our hypothesis, switching to TAF vs. remaining on TDF over 23-103 weeks did not change BMD or SUV at these key skeletal sites. The improved LS BMD in those switching to TAF is consistent with findings from other TAF-switch studies.