Faculty Collaboration Database

Decline in Bone Mass With Tenofovir Disoproxil Fumarate/Emtricitabine Is Associated With Hormonal Changes in the Absence of Renal Impairment When Used by HIV-Uninfected Adolescent Boys and Young Men for HIV Preexposure Prophylaxis. Clin Infect Dis 2017 Feb 01;64(3):317-325

Date

12/26/2016

Pubmed ID

28013265

Pubmed Central ID

PMC6366053

DOI

10.1093/cid/ciw765

Scopus ID

2-s2.0-85026913214 (requires institutional sign-in at Scopus site)   41 Citations

Abstract

BACKGROUND: We aimed to define the relative importance of renal and endocrine changes in tenofovir disoproxil fumarate (TDF)-related bone toxicity.

METHODS: In a study of daily TDF/emtricitabine (FTC) preexposure prophylaxis (PrEP) in human immunodeficiency virus (HIV)-uninfected young men who have sex with men, we measured changes from baseline in blood and urine markers of the parathyroid hormone (PTH)-vitamin D-fibroblast growth factor 23 (FGF23) axis, creatinine, and renal tubular reabsorption of phosphate (TRP). We explored the relationship of those variables to changes in bone mineral density (BMD). Tenofovir-diphosphate (TFV-DP) in red blood cells was used to categorize participants into high and low drug exposure groups.

RESULTS: There were 101 participants, median age 20 years (range 15 to 22). Compared with low drug exposure, high-exposure participants showed increase from baseline in PTH and decline in FGF23 by study week 4, with no differences in creatinine, phosphate, or TRP. At 48 weeks, the median (interquartile range) percent decline in total hip BMD was greater in those with high- compared to low- exposure (-1.59 [2.77] vs +1.54 [3.34] %, respectively; P = .001); in high-exposure participants, this correlated with week 4 TFV-DP (inversely; r = -0.60, P = .002) and FGF23 (directly; r = 0.42; P = .039) but not other variables.

CONCLUSIONS: These findings support the short-term renal safety of TDF/FTC PrEP in HIV-seronegative young men and suggest that endocrine disruption (PTH-FGF23) is a primary contributor to TDF-associated BMD decline in this age group.

CLINICAL TRIALS REGISTRATION: NCT01769469.

Author List

Havens PL, Stephensen CB, Van Loan MD, Schuster GU, Woodhouse LR, Flynn PM, Gordon CM, Pan CG, Rutledge B, Liu N, Wilson CM, Hazra R, Hosek SG, Anderson PL, Seifert SM, Kapogiannis BG, Mulligan K, Adolescent Medicine Trials Network for HIV/AIDS Interventions 117 study team

Author

Cynthia G. Pan MD Adjunct Professor in the Pediatrics department at Medical College of Wisconsin

MESH terms used to index this publication - Major topics in bold

Adolescent
Anti-HIV Agents
Bone Density
Creatinine
Emtricitabine
Glomerular Filtration Rate
HIV Infections
Homosexuality, Male
Humans
Kidney
Male
Parathyroid Hormone
Pre-Exposure Prophylaxis
Renal Insufficiency
Tenofovir
Young Adult