Switch from tenofovir to raltegravir increases low bone mineral density and decreases markers of bone turnover over 48 weeks.
BACKGROUND
Tenofovir, particularly when given with a ritonavir-boosted protease inhibitor (rPI), reduces bone mineral density (BMD) and increases bone turnover markers (BTMs), both of which are associated with increased fracture risk. Raltegravir has not been associated with bone loss.


METHODS
In an open-label, nonrandomized, pilot study, tenofovir was switched to raltegravir in adults also receiving a rPI for at least 6 months with a spine or hip T-score ≤ -1.0 and plasma HIV RNA < 50 HIV-1 RNA copies/mL for at least 3 months. The primary endpoint was BMD change by dual-energy X-ray absorptiometry. Student's paired t-test was used to compare continuous variables. Factors associated with BMD increase were assessed using linear regression.


RESULTS
Thirty-seven patients were enrolled in the study: 97% were male, the mean age was 49 years, the mean T-scores were -1.4 (spine) and -1.3 (total left hip), and the mean tenofovir treatment duration was 3.1 years. BMD increases were significant at weeks 24 and 48. At week 48, spine BMD increased by 3.0% [95% confidence interval (CI) 1.9, 4.0%; P < 0.0001] and left total hip BMD increased by 2.5% (95% CI 1.6, 3.3%; P < 0.0001). BTMs (N-telopeptide, osteocalcin and bone alkaline phosphatase) all decreased significantly at week 24 (P ≤ 0.0017). There were no raltegravir-related serious or grade 3-4 adverse events. HIV viral load remained <50 copies/mL plasma on raltegravir/rPI therapy.


CONCLUSIONS
Switching virologically suppressed HIV-infected adults with low BMD taking an rPI from tenofovir to raltegravir was safe and significantly improved hip and spine BMD and reduced markers of bone turnover over 48 weeks.
Holdsworth House Medical Practice, Sydney, NSW, Australia.
M
M
Bloch
W W Y
WW
Tong
J
J
Hoy
D
D
Baker
F J
FJ
Lee
R
R
Richardson
A
A
Carr
D015502:Absorptiometry, Photon; D000225:Adenine / Q000009:adverse effects / Q000031:analogs & derivatives*; D000328:Adult; D019380:Anti-HIV Agents / Q000009:adverse effects*; D015415:Biomarkers / Q000378:metabolism; D015519:Bone Density / Q000187:drug effects*; D057915:Drug Substitution; D005260:Female; D015497:HIV-1; D006801:Humans; D008297:Male; D008875:Middle Aged; D063065:Organophosphonates / Q000009:adverse effects*; D010384:Pelvic Bones / Q000000981:diagnostic imaging; D010865:Pilot Projects; D011760:Pyrrolidinones / Q000009:adverse effects*; D012367:RNA, Viral / Q000097:blood; D000068898:Raltegravir Potassium; D012044:Regression Analysis; D018894:Reverse Transcriptase Inhibitors / Q000009:adverse effects*; D013131:Spine / Q000000981:diagnostic imaging; D000068698:Tenofovir
D019380:Anti-HIV Agents; D015415:Biomarkers; D063065:Organophosphonates; D011760:Pyrrolidinones; D012367:RNA, Viral; D018894:Reverse Transcriptase Inhibitors; D000068898:Raltegravir Potassium; D000068698:Tenofovir; D000225:Adenine
HIV; bone turnover; low bone mineral density; raltegravir; tenofovir