2188. Bone Mineral Density (BMD) Reductions after Tenofovir Disoproxil Fumarate (TDF) Initiation Are Not Associated with Changes in Phosphaturia: A Secondary Analysis of ACTG A5224s
Session: Poster Abstract Session: HIV Renal and Bones
Saturday, October 29, 2016
Room: Poster Hall
  • IDWeek 2016 Poster 2188.pdf (1.2 MB)
  • Background: In ACTG A5224s, TDF use led to greater reductions in BMD compared to abacavir (ABC) use. This risk has been presumed to be due to increased phosphaturia linked with TDF use, although evidence is lacking to support this hypothesis. An alternative hypothesis is that greater circulating exposure to tenofovir (TFV) may directly impair bone homeostasis.

    Methods: We tested these competing hypotheses by correlating changes in BMD at the hip and spine with changes in phosphaturia [assessed by transtubular reabsorption of phosphorus (TRP) and tubular maximum phosphate reabsorption per glomerular filtration rate (TmP/GFR)] from baseline through week 96 in those receiving regimens containing TDF (n=134) vs ABC (n=135) with efavirenz (EFV) or atazanavir/ritonavir (ATV/r ), in A5224s. We also correlated changes in BMD with plasma TFV exposure [TFV area under the curve (AUC) measured through sparse PK between weeks 2 and 24]. Statistical testing used linear regression and Spearman’s correlation at the α=0.05 level with no adjustment for multiple comparisons.

    Results: Changes in TRP and TmP/GFR through week 96 between the TDF and ABC arms were not significantly different (both p≥0.70) and had no interactions with use of EFV vs ATV/r. There were statistically significant inverse correlations between TRP and hip BMD (but not spine) overall at weeks 24 (r= -0.17, p=0.013) and 48 (r= -0.17, p=0.020) but not at week 96 (r = -0.06, p=0.47). There were no significant correlations between changes in either TRP or TmP/GFR and with either hip or spine BMD in the TDF arms through week 96. TFV AUC was significantly correlated with changes in hip BMD, but not spine BMD, at week 24 (r = -0.22, p=0.028) and week 48 (r = -0.26, p=0.010) but not at week 96 (r= -0.14, p=0.18). Changes in TRP and TmP/GFR at 24 week were not significantly correlated with TFV AUC.

    Conclusion: Changes in phosphaturia were not different between the TDF and ABC arms in A5224s. Changes in hip and spine BMD with TDF were not related to changes in phosphaturia but rather to TFV exposure, albeit only weakly at the hip through week 48. Reductions in circulating concentrations of TFV, such as with reduced dosing of TDF or with use of tenofovir alafenamide, may limit initial declines in hip BMD in HIV-infected patients.

    Samir Gupta, MD, MS, Medicine/Infectious Diseases, Indiana University School of Medicine, Indianapolis, IN, Eunice Yeh, BSPH, Center for Biostatistics in AIDS Research, Harvard T.H. Chan School of Public Health, Boston, MA, Douglas Kitch, MS, XXX, Boston, MA, Todd Brown, MD, PhD, Johns Hopkins University, Baltimore, MD, Charles Venuto, PhD, University of Rochester Medical Center, Rochester, NY, Gene Morse, PharmD, Translational Pharmacology Research Core, NYS Center of Excellence in Bioinformatics and Life Sciences, School of Pharmacy and Pharmaceutical Sciences, University at Buffalo, Buffalo, NY, Belinda Ha, PhD, ViiV Healthcare, Research Triangle Park, NC, Kathy Melbourne, PharmD, AAHIVP, Gilead Sciences, Foster City, CA and Grace Mccomsey, MD, FIDSA, Pediatrics and Medicine, Case Western Reserve University, Cleveland, OH


    S. Gupta, Gilead Sciences: Grant Investigator , Investigator and Scientific Advisor , Consulting fee , Research grant , Research support and Travel support to scientific conferences
    Bristol-Myers Squibb: Investigator , Research support and Travel support to scientific conferences
    Janssen Therapeutics: Grant Investigator and Investigator , Research grant and Research support

    E. Yeh, None

    D. Kitch, None

    T. Brown, Gilead: Consultant and Scientific Advisor , Honoraria

    C. Venuto, None

    G. Morse, None

    B. Ha, ViiV Healthcare: Employee , Salary

    K. Melbourne, Gilead Sciences: Employee , Salary

    G. Mccomsey, Gilead: Consultant , Grant Investigator and Scientific Advisor , Consulting fee and Research grant
    BMS: Consultant and Grant Investigator , Consulting fee and Research grant
    Viiv/GSK: Consultant and Grant Investigator , Consulting fee and Research grant

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