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Improved Low Bone Mineral Density and Bone Turnover Markers with Switch from Tenofovir to Raltegravir in Virologically Suppressed HIV-1+ Adults at 48 Weeks: The TROP Study
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Reported by Jules Levin
CROI 2012 March 5-8 Seattle WA
Mark Bloch1*, Winnie Tong2, Jennifer Hoy3, Robyn Richardson2, David Baker4, Andrew Carr2
1Holdsworth House Medical Practice, Sydney, 2 St Vincent's Centre for Applied Medical Research, St Vincent's Hospital, Sydney,
3The Alfred Hospital and Monash University, Melbourne, 4East Sydney Doctors, Sydney, Australia
Background: Antiretroviral therapy (ART), particularly tenofovir (TDF), has been associated with decreased bone mineral density (BMD) and fracture risk. There is no published data on the effect of raltegravir (RAL) on BMD. Increased plasma bone turnover markers (BTM) are associated with accelerated bone loss.
Methods: In an open-label, non-randomised, 48-week study, TDF was switched to RAL while maintaining ritonavir-boosted protease inhibitor (rPI) in HIV+ adults with spine or hip T-score ≤1.0, plasma HIV RNA <50 cp/ml for ≥3 months and on TDF and rPI for ≥6 months. The primary endpoint was BMD change from baseline at 48 weeks by dual-energy x-ray absorptiometry. Secondary endpoints included BTMs, HIV viral load and safety. Sample size was calculated to detect a 2% change in BMD with 90% power. Paired t-test was used to compare continuous variables.
Results: Of 37 patients enrolled, 97% were male, mean age 49 years, 84% Caucasian, 32% smokers, mean T-score -1.4 (spine) and -1.3 (total left hip), mean duration of HIV infection and TDF therapy 14.6 and 3.1 years, respectively. BMD increased and BTMs decreased significantly at week 48 (Table).
There was a modest decrease in 10-year probability of hip fracture by FRAX score at week 48 (0.90% to 0.78%, p=0.045) but no significant decrease in 10-year probability of major osteoporotic fracture. Vitamin D levels remained stable over 48 weeks. RAL was well tolerated, with no related serious, grade 3 or grade 4 adverse events, and was ceased in only 2 participants, who interrupted all therapy for pill burden or adverse event after week 36. Both resuppressed to <50 cp/ml on RAL-rPI therapy after week 48.
Conclusions: These pilot data suggest that switching TDF to RAL in aviraemic osteopenic or osteoporotic HIV+ adults on TDF-rPI after a mean 3 yrs TDF therapy is safe and significantly improves BMD and reduces bone turnover over 48 weeks at both the spine and hip.
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