Journal
ANTIVIRAL THERAPY
Volume 16, Issue 7, Pages 1063-1072Publisher
INT MEDICAL PRESS LTD
DOI: 10.3851/IMP1874
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Funding
- GlaxoSmithKline
- NIH [5K23AT002862-03]
- Case Western Reserve University Center for AIDS Research [NIH AI36219]
- Johns Hopkins Bayview GCRC Advanced Chemistry Laboratory [NIH ICTR 5UL1RR02500.5-02]
- Bristol-Myers Squibb
- Gilead
- Merck
- ViiV Healthcare
- Tibotec
- Abbott
- Data Safety Monitor Board for a Pfizer
- Cubist Pharmaceuticals
- NATIONAL CENTER FOR COMPLEMENTARY &ALTERNATIVE MEDICINE [K23AT002862] Funding Source: NIH RePORTER
- NATIONAL CENTER FOR RESEARCH RESOURCES [UL1RR025005] Funding Source: NIH RePORTER
- NATIONAL INSTITUTE OF ALLERGY AND INFECTIOUS DISEASES [P30AI036219] Funding Source: NIH RePORTER
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Background: Bone mineral density decreases with antiretroviral therapy (ART) initiation, although the pathogenesis, including the role of tenofovir (TDF), is unclear. This study assessed changes in bone-turnover markers, osteoprotegerin (OPG), soluble receptor activator for nuclear factor-kappa beta ligand (sRANKL), and inflammation in subjects initiating TDF- versus non-TDF-containing regimens, and determined the relationship between bone turnover, OPG/sRANKL and inflammation. Methods: This was a longitudinal observational study comparing levels of bone turnover markers (C-terminal telopeptide of type I collagen [CTX] and osteocalcin [OC]), OPG, sRANKL and inflammatory cytokines (soluble tumour necrosis factor [TNF]-alpha receptor [sTNFR]-I, sTNFR-II and interleukin-6) prior to ART and 6-12 months after ART initiation with a TDF- versus non-TDF-containing regimen in HIV-infected subjects 18-50 years old. Results: A total of 87 subjects were enrolled (TDF n=44 and non-TDF n=43). Groups were similar except subjects on TDF had a lower CD4(+) T-cell nadir (P<0.01) and were more likely to receive a protease inhibitor (PI; P=0.03). At pre-ART, 35% and 1% of subjects had CTX and OC above the normal range, respectively. Both increased with ART initiation, whereas OPG, sRANKL and inflammatory markers significantly decreased. In multivariate models, increases in OC were associated with TDF use, PI use and pre-ART levels of sTNFR-I, whereas increases in CTX were associated with CD4(+) T-cell nadir <50 cell/mm(3). Increases in bone markers were unrelated to pre-ART levels of OPG/sRANKL and changes in OPG/sRANKL after ART initiation. Conclusions: TDF use, PI use, TNF-alpha activity and advanced HIV disease are associated with changes in bone turnover markers, underscoring the complicated interaction between ART, bone turnover, inflammation and immune status, which extend beyond the OPG/RANKL system.
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