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Impact of Tenofovir-Based Pre-exposure Prophylaxis on Biomarkers of Bone Formation, Bone Resorption, and Bone Mineral Metabolism in HIV-Negative Adults.

ABSTRACT: Background:Pre-exposure prophylaxis (PrEP) with emtricitabine (FTC)/tenofovir disoproxil fumarate (TDF) reduces the risk of HIV seroconversion but may promote bone mineral density (BMD) decline. The mechanisms of BMD decline with FTC/TDF remain unclear, and studies in HIV-positive individuals have been confounded by the effects of HIV and concomitant antiretroviral medications. We evaluated the impact of FTC/TDF on biomarkers of bone remodeling and bone mineral metabolism in HIV-negative men and women enrolled in the Partners PrEP Study. Methods:In a random sample of HIV-negative participants randomized to FTC/TDF PrEP (n = 50) or placebo (n = 50), serum parathyroid hormone (PTH), bone biomarkers (C-telopeptide, procollagen 1 intact N-terminal propeptide, and sclerostin), and plasma fibroblast growth factor 23 were measured at baseline and month 24, and the percentage change was compared between groups. In a complementary analysis, we compared the change in biomarkers between participants with and without a 25% decline in glomerular filtration rate (GFR) on FTC/TDF. Results:Baseline characteristics were similar between the groups (median age, 38 years; 40% women). Vitamin D insufficiency was common, but baseline GFR and PTH were in the normal range. We observed a significantly greater percent increase in serum C-telopeptide in participants randomized to FTC/TDF vs placebo (P = .03), suggesting an increase in bone remodeling. We observed no differences in the other biomarkers, or in a separate analysis comparing participants with and without a decline in GFR. Conclusions:Increased bone remodeling may mediate the BMD decline observed with tenofovir-containing PrEP and antiretroviral therapy, independent of a TDF-mediated decrease in kidney function.

SUBMITTER: Nickolas TL

PROVIDER: S-EPMC6778426 | biostudies-literature | 2019 Oct

REPOSITORIES: biostudies-literature

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Impact of Tenofovir-Based Pre-exposure Prophylaxis on Biomarkers of Bone Formation, Bone Resorption, and Bone Mineral Metabolism in HIV-Negative Adults.

Nickolas Thomas L TL Yin Michael T MT Hong Ting T Mugwanya Kenneth K KK Branch Andrea D AD Heffron Renee R Ramalho Janaina J Nandakumar Renu R Dworakowski Elzbieta E Wanga Valentine V Mugo Nelly R NR Ronald Allan A Celum Connie C Donnell Deborah D Baeten Jared M JM Wyatt Christina M CM

Open forum infectious diseases 20190728 10

<h4>Background</h4>Pre-exposure prophylaxis (PrEP) with emtricitabine (FTC)/tenofovir disoproxil fumarate (TDF) reduces the risk of HIV seroconversion but may promote bone mineral density (BMD) decline. The mechanisms of BMD decline with FTC/TDF remain unclear, and studies in HIV-positive individuals have been confounded by the effects of HIV and concomitant antiretroviral medications. We evaluated the impact of FTC/TDF on biomarkers of bone remodeling and bone mineral metabolism in HIV-negative ...[more]

PMID: 31660332

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Project description:IntroductionTenofovir disoproxil fumarate with emtricitabine (TDF/FTC) is used for HIV pre-exposure prophylaxis (PrEP). TDF may affect bone mineral density (BMD), particularly in youth who are at a stage of peak bone mass accrual. The objective of this study was to evaluate the effect of vitamin D and calcium supplementation on BMD among Thai youth receiving daily oral PrEP.MethodsThis open-label randomized trial was conducted in male youth aged between 15 and 24 years. Participants were randomized to Arm A who received once-daily TDF/FTC plus vitamin D3 and calcium supplementation with meals twice daily (400 units of vitamin D3 and 1200 mg of elemental calcium/day) or Arm B who received once-daily TDF/FTC only. PrEP users were defined as taking at least two tablets/week (tenofovir-diphosphate level of >350 fmol/punch). Adherence to vitamin D/calcium supplementation was defined as self-reported adherence of >50%. Lumbar spine (L2-L4) BMD (LSBMD) was evaluated by dual-energy X-ray absorptiometry scan zero and six months after PrEP initiation.ResultsFrom March 2019 to March 2020, 100 youth were enrolled. Baseline characteristics between the two arms were similar. Median (IQR) age was 18 (17 to 20) years. At entry, median (IQR) LSBMD z-score was -0.8 (-1.5 to -0.3), 17% had low LSBMD (Z-score < -2). The median amount of calcium intake from nutritional three-day recall was 167 (IQR 94 to 272) mg/day, 39% of participants had vitamin D deficiency, defined as 25(OH)D levels <20 IU/mL. At six months, 79 participants were evaluated. Of these, 42 (52%) were PrEP takers and 25 of 38 (66%) of arm A participants had good adherence to vitamin D/calcium supplementation. Significantly higher proportions of youth in arm A compared to arm B had >3% increase in LSBMD at month 6 compared to baseline (67.6% vs. 42.9% respectively; p = 0.03). There were significantly higher increases in LSBMD among youth with vitamin D deficiency who were supplemented; arm A + 0.05 (0 to 0.05) compared to arm B + 0.03 (-0.1 to 0.03), p = 0.04.ConclusionsIncreases in LSBMD over six months among youth using PrEP who received vitamin D/calcium supplementation was greater than those not supplemented. Long-term follow-up should be considered to explore long-term outcomes.

Dataset Information

Impact of Tenofovir-Based Pre-exposure Prophylaxis on Biomarkers of Bone Formation, Bone Resorption, and Bone Mineral Metabolism in HIV-Negative Adults.

Publications

Impact of Tenofovir-Based Pre-exposure Prophylaxis on Biomarkers of Bone Formation, Bone Resorption, and Bone Mineral Metabolism in HIV-Negative Adults.

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