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

Thomas L. Nickolas, Michael T. Yin, Ting Hong, Kenneth K. Mugwanya, Andrea D. Branch, Renee Heffron, Janaina Ramalho, Renu Nandakumar, Elzbieta Dworakowski, Valentine Wanga, Nelly R. Mugo, Allan Ronald, Connie Celum, Deborah Donnell, Jared M. Baeten, Christina M. Wyatt, Robert W. Coombs, Lisa Frenkel, Craig W. Hendrix, Jairam R. LingappaM. Juliana McElrath, Kenneth H. Fife, Edwin Were, Elioda Tumwesigye, Patrick Ndase, Elly Katabira, Elizabeth Bukusi, Craig R. Cohen, Jonathan Wangisi, James D. Campbell, Jordan W. Tappero, James Kiarie, Carey Farquhar, Grace John-Stewart

Research output: Contribution to journalArticle

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.

Original languageEnglish (US)
Article numberofz338
JournalOpen Forum Infectious Diseases
Volume6
Issue number10
DOIs
StatePublished - Sep 30 2019

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Tenofovir
Bone Resorption
Osteogenesis
Minerals
Biomarkers
HIV
Bone and Bones
Bone Remodeling
Glomerular Filtration Rate
Bone Density
Parathyroid Hormone
Placebos
HIV Seropositivity
Procollagen
Pre-Exposure Prophylaxis
Serum
Vitamin D

Keywords

  • antiretroviral therapy
  • bone turnover
  • HIV prevention
  • kidney
  • tubular dysfunction

ASJC Scopus subject areas

  • Oncology
  • Clinical Neurology

Cite this

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.; Yin, Michael T.; Hong, Ting; Mugwanya, Kenneth K.; Branch, Andrea D.; Heffron, Renee; Ramalho, Janaina; Nandakumar, Renu; Dworakowski, Elzbieta; Wanga, Valentine; Mugo, Nelly R.; Ronald, Allan; Celum, Connie; Donnell, Deborah; Baeten, Jared M.; Wyatt, Christina M.; Coombs, Robert W.; Frenkel, Lisa; Hendrix, Craig W.; Lingappa, Jairam R.; McElrath, M. Juliana; Fife, Kenneth H.; Were, Edwin; Tumwesigye, Elioda; Ndase, Patrick; Katabira, Elly; Bukusi, Elizabeth; Cohen, Craig R.; Wangisi, Jonathan; Campbell, James D.; Tappero, Jordan W.; Kiarie, James; Farquhar, Carey; John-Stewart, Grace.

In: Open Forum Infectious Diseases, Vol. 6, No. 10, ofz338, 30.09.2019.

Research output: Contribution to journalArticle

Nickolas, TL, Yin, MT, Hong, T, Mugwanya, KK, Branch, AD, Heffron, R, Ramalho, J, Nandakumar, R, Dworakowski, E, Wanga, V, Mugo, NR, Ronald, A, Celum, C, Donnell, D, Baeten, JM, Wyatt, CM, Coombs, RW, Frenkel, L, Hendrix, CW, Lingappa, JR, McElrath, MJ, Fife, KH, Were, E, Tumwesigye, E, Ndase, P, Katabira, E, Bukusi, E, Cohen, CR, Wangisi, J, Campbell, JD, Tappero, JW, Kiarie, J, Farquhar, C & John-Stewart, G 2019, 'Impact of Tenofovir-Based Pre-exposure Prophylaxis on Biomarkers of Bone Formation, Bone Resorption, and Bone Mineral Metabolism in HIV-Negative Adults', Open Forum Infectious Diseases, vol. 6, no. 10, ofz338. https://doi.org/10.1093/ofid/ofz338
Nickolas, Thomas L. ; Yin, Michael T. ; Hong, Ting ; Mugwanya, Kenneth K. ; Branch, Andrea D. ; Heffron, Renee ; Ramalho, Janaina ; Nandakumar, Renu ; Dworakowski, Elzbieta ; Wanga, Valentine ; Mugo, Nelly R. ; Ronald, Allan ; Celum, Connie ; Donnell, Deborah ; Baeten, Jared M. ; Wyatt, Christina M. ; Coombs, Robert W. ; Frenkel, Lisa ; Hendrix, Craig W. ; Lingappa, Jairam R. ; McElrath, M. Juliana ; Fife, Kenneth H. ; Were, Edwin ; Tumwesigye, Elioda ; Ndase, Patrick ; Katabira, Elly ; Bukusi, Elizabeth ; Cohen, Craig R. ; Wangisi, Jonathan ; Campbell, James D. ; Tappero, Jordan W. ; Kiarie, James ; Farquhar, Carey ; John-Stewart, Grace. / Impact of Tenofovir-Based Pre-exposure Prophylaxis on Biomarkers of Bone Formation, Bone Resorption, and Bone Mineral Metabolism in HIV-Negative Adults. In: Open Forum Infectious Diseases. 2019 ; Vol. 6, No. 10.
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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.",
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author = "Nickolas, {Thomas L.} and Yin, {Michael T.} and Ting Hong and Mugwanya, {Kenneth K.} and Branch, {Andrea D.} and Renee Heffron and Janaina Ramalho and Renu Nandakumar and Elzbieta Dworakowski and Valentine Wanga and Mugo, {Nelly R.} and Allan Ronald and Connie Celum and Deborah Donnell and Baeten, {Jared M.} and Wyatt, {Christina M.} and Coombs, {Robert W.} and Lisa Frenkel and Hendrix, {Craig W.} and Lingappa, {Jairam R.} and McElrath, {M. Juliana} and Fife, {Kenneth H.} and Edwin Were and Elioda Tumwesigye and Patrick Ndase and Elly Katabira and Elizabeth Bukusi and Cohen, {Craig R.} and Jonathan Wangisi and Campbell, {James D.} and Tappero, {Jordan W.} and James Kiarie and Carey Farquhar and Grace John-Stewart",
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T1 - Impact of Tenofovir-Based Pre-exposure Prophylaxis on Biomarkers of Bone Formation, Bone Resorption, and Bone Mineral Metabolism in HIV-Negative Adults

AU - Nickolas, Thomas L.

AU - Yin, Michael T.

AU - Hong, Ting

AU - Mugwanya, Kenneth K.

AU - Branch, Andrea D.

AU - Heffron, Renee

AU - Ramalho, Janaina

AU - Nandakumar, Renu

AU - Dworakowski, Elzbieta

AU - Wanga, Valentine

AU - Mugo, Nelly R.

AU - Ronald, Allan

AU - Celum, Connie

AU - Donnell, Deborah

AU - Baeten, Jared M.

AU - Wyatt, Christina M.

AU - Coombs, Robert W.

AU - Frenkel, Lisa

AU - Hendrix, Craig W.

AU - Lingappa, Jairam R.

AU - McElrath, M. Juliana

AU - Fife, Kenneth H.

AU - Were, Edwin

AU - Tumwesigye, Elioda

AU - Ndase, Patrick

AU - Katabira, Elly

AU - Bukusi, Elizabeth

AU - Cohen, Craig R.

AU - Wangisi, Jonathan

AU - Campbell, James D.

AU - Tappero, Jordan W.

AU - Kiarie, James

AU - Farquhar, Carey

AU - John-Stewart, Grace

PY - 2019/9/30

Y1 - 2019/9/30

N2 - 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.

AB - 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.

KW - antiretroviral therapy

KW - bone turnover

KW - HIV prevention

KW - kidney

KW - tubular dysfunction

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DO - 10.1093/ofid/ofz338

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