Format

Send to

Choose Destination
Clin Infect Dis. 2017 Feb 1;64(3):317-325. doi: 10.1093/cid/ciw765. Epub 2016 Nov 15.

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.

Author information

1
Department of Pediatrics, Medical College of Wisconsin/Children's Hospital of Wisconsin, Milwaukee; phavens@mcw.edu.
2
US Department of Agriculture, Agricultural Research Service, Western Human Nutrition Research Center, and.
3
Department of Nutrition, University of California, Davis.
4
Department of Infectious Diseases, St. Jude Children's Research Hospital, Memphis, Tennessee.
5
Department of Pediatrics, University of Cincinnati College of Medicine/Cincinnati Children's Hospital Medical Center, Ohio.
6
Department of Pediatrics, Medical College of Wisconsin/Children's Hospital of Wisconsin, Milwaukee.
7
Westat, Rockville, Maryland.
8
Department of Epidemiology, University of Alabama at Birmingham.
9
Maternal and Pediatric Infectious Disease Branch, Eunice Kennedy Shriver National Institute of Child Health and Human Development, Bethesda, Maryland.
10
Department of Psychiatry, Stroger Hospital of Cook County, Chicago, Illinois.
11
Department of Pharmaceutical Sciences, University of Colorado Anschutz Medical Campus, Aurora; and.
12
Department of Medicine, Division of Endocrinology, Zuckerberg San Francisco General Hospital, University of California, San Francisco.

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.

KEYWORDS:

HIV pre- exposure prophylaxis.; bone mineral density; fibroblast growth factor 23; parathyroid hormone; tenofovir disoproxil fumarate

PMID:
28013265
DOI:
10.1093/cid/ciw765
[Indexed for MEDLINE]

Supplemental Content

Full text links

Icon for Silverchair Information Systems
Loading ...
Support Center