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Mechanism of Bone Disease in HIV and HCV:
Impact of Tenofovir Exposure and Severity of Liver Disease
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Reported by Jules Levin
CROI 2014 March 3-6 Boston, MA
James Cutrell1,2, Naim Maalouf2, Song Zhang2, Henning Drechsler1,2, Ang Gao2, Pablo Tebas3, Roger Bedimo1,2 1VA North Texas Health Care System, Dallas, TX, 2University of Texas Southwestern, Dallas, TX, 3University of Pennsylvania, Philadelphia, PA
Program Abstract
Background: Both HIV and HCV infections are associated with an increased risk of osteoporotic fractures. The mechanisms underlying this higher risk are
incompletely elucidated. In this analysis, we explore the effects of HIV, HCV and HIV/HCV co-infection on bone health, and assess the relative contributions
of TDF exposure and severity of liver disease.
Methodology: This prospective, cross-sectional study recruited 298 male volunteers with HIV, HCV, HIV/HCV co-infection and non-infected controls. All
HIV infected patients were virologically suppressed on HAART. Subjects underwent bone mineral density (BMD) testing by DXA scan and measurement
of fasting bone turnover markers (BTM) (serum C-telopeptide [CTX] and osteocalcin [OC]). The aspartate aminotransferase-to-platelet ratio (APRI) score
was calculated as an indirect marker of hepatic fibrosis. Impact of HIV and HCV infections on BMD was evaluated in multivariate models adjusting for APRI
score, BTM, TDF exposure (current, past or never), or duration of TDF use, respectively. All models controlled for age, race and BMI.
Results: Table 1 presents the multivariate analyses of the associations of HIV and HCV infections on femoral neck BMD. HIV and HCV independently predict
lower femoral neck BMD, controlling for age, race and BMI (model 1). APRI did not significantly impact BMD or attenuate the association between HIV or
HCV and BMD (Model 2), with similar results observed when analysis was restricted to HCV and HIV/HCV patients (not shown). The effect of HIV on BMD
is likely mediated through increased bone turnover: HIV patients had higher levels of CTX (p<0.005) and OC (p<0.001). Furthermore, controlling for OC
(model 3) or CTX (not shown) attenuated the association of HIV with BMD. HCV infection did not impact OC or CTX, but was associated with increases in
regulatory cytokines OPG (p<0.001) and RANKL (p<0.005). Among HIV and HIV/HCV patients, TDF exposure (current or past) (model 4) and duration of
TDF use were associated with lower BMD (p=0.0234). After controlling for TDF exposure, the association of HIV disease with lower BMD was significantly
attenuated, suggesting that the observed HIV impact is largely mediated by TDF exposure. Similar associations were observed for total hip BMD.
Conclusions: The impact of HIV on BMD appears to be explained (at least in large part) by TDF exposure and higher bone turnover. HCV association with
BMD is independent of the severity of liver disease, as measured by APRI score.
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