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  17th International Workshop
on Clinical Pharmacology of
HIV and Hepatitis Therapy
June 8-10, 2016, Washington DC
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Cumulative Tenofovir Level Tied to Lower Spine BMD in Young Adults
  17th International Workshop on Clinical Pharmacology of HIV and Hepatitis Therapy, June 8-10, 2016, Washington DC
Mark Mascolini
In young adults taking tenofovir disoproxil fumarate (TDF), cumulative exposure was linked to lower spine bone mineral density (BMD), while using a ritonavir-boosted protease inhibitor (PI) was tied to lower hip BMD in HIV-positive people older than 60 [1].
Drops in BMD during TDF therapy are well documented, but University of Colorado Denver researchers who conducted this study noted difficulties in assessing overall TDF exposure, which cannot rely on plasma concentrations alone. Because tenofovir has a long intracellular half-life, they decided to assess tenofovir-diphosphate (TFV-DP) exposure in dried blood spots in younger and older adults with HIV. They explained that intracellular TFV-DP "offers an objective and quantitative measure of cumulative dosing indicative of TDF exposure over a 1-2 month period."
The study involved virally suppressed adults in two age groups: 18 to 35 and over 60. Everyone had taken TDF for at least 1 year, and all gave whole blood samples that technicians spotted onto Protein Saver Cards for dried blood spot analysis. All study participants had DXA scans of the lumbar spine, hip, and whole body.
The researchers enrolled 23 people in the younger age group and 22 in the older group. There were 2 women in each age group, 6 African Americans (2 younger, 4 older), and 14 people taking a ritonavir-boosted PI (5 younger, 9 older). TDF duration averaged 3.8 years in the younger group and 4.9 years in the older group. Respective blood spot steady-state concentrations were 2136 and 2341 fmol/punch. BMD did not differ significantly between groups at the spine or hip.
Univariate regression analysis established that TFV-DP steady-state concentration was negatively associated with lumbar spine BMD in the younger people--the higher the concentration, the lower the BMD (P = 0.01). Multivariable regression determined that the relationship between spine BMD and TFV-DP differed significantly by age (P = 0.01). With every 100-fmol/punch increase in TFV-DP, spine BMD dropped an average 0.007 g/cm(2) in the younger cohort (P = 0.009) but rose an average 0.002 g/cm(2) in the older cohort, a nonsignificant relationship (P = 0.407).
Univariate analysis established a 0.0042 g/cm(2) decline in hip BMD for every 100 fmol/punch higher TFV-DP level (P = 0.032), but adjustment for lean mass and age attenuated that result. A model adjusted for lean mass and TFV-DP level determined that older people taking a PI had a 0.11 g/cm(2) lower hip BMD than those not taking a PI (P = 0.008). But PI use did not affect hip BMD in young participants.
On the basis of these results, the Colorado team proposed that measures of cumulative TFV exposure may predict the degree of BMD decline in virally suppressed people taking TDF.
1. Seifert SM, Castillo-Mancilla JR, Erlandson KM, et al. Cumulative tenofovir exposure is associated with decreased BMD in young and old HIV-infected adults on tenofovir based regimens. 17th International Workshop on Clinical Pharmacology of HIV and Hepatitis Therapy, June 8-10, 2016, Washington DC. Abstract O9.