Low Risk of Proximal Tubular Dysfunction Associated with Emtricitabine-Tenofovir Disoproxil Fumarate Preexposure Prophylaxis in Men and Women

Kenneth Mugwanya, Jared Baeten, Connie Celum, Deborah Donnell, Thomas Nickolas, Nelly Mugo, Andrea Branch, Jordan Tappero, James Kiarie, Allan Ronald, Michael Yin, Christina Wyatt, Jared M. Baeten, Robert W. Coombs, Lisa Frenkel, Craig W. Hendrix, Jairam R. Lingappa, M. Juliana McElrath, Kenneth Fife, Kenneth H. FifeEdwin Were, Elioda Tumwesigye, Patrick Ndase, Elly Katabira, Elizabeth Bukusi, Craig R. Cohen, Jonathan Wangisi, James D. Campbell, Jordan W. Tappero, Carey Farquhar, Grace John-Stewart, Nelly R. Mugo

Research output: Contribution to journalArticle

16 Citations (Scopus)

Abstract

Objective.Tenofovir disoproxil fumarate (TDF) is associated with proximal tubular dysfunction (tubulopathy) when used in the treatment of human immunodeficiency virus (HIV) infection. We evaluated whether TDF causes tubulopathy when used as HIV preexposure prophylaxis (PrEP) and whether tubulopathy predicts clinically relevant decline (≥25%) in the estimated glomerular filtration rate (eGFR). Methods.A subgroup analysis of the Partners PrEP Study, a randomized, placebo-controlled trial of daily oral TDF, alone or with emtricitabine (FTC), in HIV-uninfected African men and women (Clinicaltrials.gov NCT00557245). Tubulopathy was assessed in concurrently obtained urine and serum samples at the 24-month or last on-treatment visit, predefined as ≥2 of the following: tubular proteinuria, euglycemic glycosuria, increased urinary phosphate, and uric acid excretion. Results.Of 1549 persons studied (776 receiving FTC-TDF, 773 receiving placebo), 64% were male, and the median age was 37 years. Over a median 24 months of study-drug exposure, the frequency of tubulopathy was 1.7% for FTC-TDF versus 1.3% for placebo (odds ratio, 1.30; 95% confidence interval,. 52-3.33; P =. 68); Tubulopathy occurred in 2 of 52 persons (3.8%) with versus 3 of 208 (1.4%) without ≥25% eGFR decline (adjusted odds ratio, 1.39;. 10-14.0; P >. 99). Conclusions.Daily oral FTC-TDF PrEP was not significantly associated with tubulopathy over the course of 24 months, nor did tubulopathy predict clinically relevant eGFR decline.

Original languageEnglish (US)
Pages (from-to)1050-1057
Number of pages8
JournalJournal of Infectious Diseases
Volume214
Issue number7
DOIs
StatePublished - Oct 1 2016

Fingerprint

Tenofovir
Glomerular Filtration Rate
Placebos
HIV
Odds Ratio
Glycosuria
Virus Diseases
Uric Acid
Proteinuria
Emtricitabine
Randomized Controlled Trials
Phosphates
Urine

Keywords

  • PrEP
  • proximal tubular dysfunction
  • TDF nephrotoxicity
  • TDF toxicity

ASJC Scopus subject areas

  • Immunology and Allergy
  • Infectious Diseases

Cite this

Low Risk of Proximal Tubular Dysfunction Associated with Emtricitabine-Tenofovir Disoproxil Fumarate Preexposure Prophylaxis in Men and Women. / Mugwanya, Kenneth; Baeten, Jared; Celum, Connie; Donnell, Deborah; Nickolas, Thomas; Mugo, Nelly; Branch, Andrea; Tappero, Jordan; Kiarie, James; Ronald, Allan; Yin, Michael; Wyatt, Christina; Baeten, Jared M.; Coombs, Robert W.; Frenkel, Lisa; Hendrix, Craig W.; Lingappa, Jairam R.; McElrath, M. Juliana; Fife, Kenneth; Fife, Kenneth H.; Were, Edwin; Tumwesigye, Elioda; Ndase, Patrick; Katabira, Elly; Bukusi, Elizabeth; Cohen, Craig R.; Wangisi, Jonathan; Campbell, James D.; Tappero, Jordan W.; Farquhar, Carey; John-Stewart, Grace; Mugo, Nelly R.

In: Journal of Infectious Diseases, Vol. 214, No. 7, 01.10.2016, p. 1050-1057.

Research output: Contribution to journalArticle

Mugwanya, K, Baeten, J, Celum, C, Donnell, D, Nickolas, T, Mugo, N, Branch, A, Tappero, J, Kiarie, J, Ronald, A, Yin, M, Wyatt, C, Baeten, JM, Coombs, RW, Frenkel, L, Hendrix, CW, Lingappa, JR, McElrath, MJ, Fife, K, Fife, KH, Were, E, Tumwesigye, E, Ndase, P, Katabira, E, Bukusi, E, Cohen, CR, Wangisi, J, Campbell, JD, Tappero, JW, Farquhar, C, John-Stewart, G & Mugo, NR 2016, 'Low Risk of Proximal Tubular Dysfunction Associated with Emtricitabine-Tenofovir Disoproxil Fumarate Preexposure Prophylaxis in Men and Women', Journal of Infectious Diseases, vol. 214, no. 7, pp. 1050-1057. https://doi.org/10.1093/infdis/jiw125
Mugwanya, Kenneth ; Baeten, Jared ; Celum, Connie ; Donnell, Deborah ; Nickolas, Thomas ; Mugo, Nelly ; Branch, Andrea ; Tappero, Jordan ; Kiarie, James ; Ronald, Allan ; Yin, Michael ; Wyatt, Christina ; Baeten, Jared M. ; Coombs, Robert W. ; Frenkel, Lisa ; Hendrix, Craig W. ; Lingappa, Jairam R. ; McElrath, M. Juliana ; Fife, Kenneth ; Fife, Kenneth H. ; Were, Edwin ; Tumwesigye, Elioda ; Ndase, Patrick ; Katabira, Elly ; Bukusi, Elizabeth ; Cohen, Craig R. ; Wangisi, Jonathan ; Campbell, James D. ; Tappero, Jordan W. ; Farquhar, Carey ; John-Stewart, Grace ; Mugo, Nelly R. / Low Risk of Proximal Tubular Dysfunction Associated with Emtricitabine-Tenofovir Disoproxil Fumarate Preexposure Prophylaxis in Men and Women. In: Journal of Infectious Diseases. 2016 ; Vol. 214, No. 7. pp. 1050-1057.
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abstract = "Objective.Tenofovir disoproxil fumarate (TDF) is associated with proximal tubular dysfunction (tubulopathy) when used in the treatment of human immunodeficiency virus (HIV) infection. We evaluated whether TDF causes tubulopathy when used as HIV preexposure prophylaxis (PrEP) and whether tubulopathy predicts clinically relevant decline (≥25{\%}) in the estimated glomerular filtration rate (eGFR). Methods.A subgroup analysis of the Partners PrEP Study, a randomized, placebo-controlled trial of daily oral TDF, alone or with emtricitabine (FTC), in HIV-uninfected African men and women (Clinicaltrials.gov NCT00557245). Tubulopathy was assessed in concurrently obtained urine and serum samples at the 24-month or last on-treatment visit, predefined as ≥2 of the following: tubular proteinuria, euglycemic glycosuria, increased urinary phosphate, and uric acid excretion. Results.Of 1549 persons studied (776 receiving FTC-TDF, 773 receiving placebo), 64{\%} were male, and the median age was 37 years. Over a median 24 months of study-drug exposure, the frequency of tubulopathy was 1.7{\%} for FTC-TDF versus 1.3{\%} for placebo (odds ratio, 1.30; 95{\%} confidence interval,. 52-3.33; P =. 68); Tubulopathy occurred in 2 of 52 persons (3.8{\%}) with versus 3 of 208 (1.4{\%}) without ≥25{\%} eGFR decline (adjusted odds ratio, 1.39;. 10-14.0; P >. 99). Conclusions.Daily oral FTC-TDF PrEP was not significantly associated with tubulopathy over the course of 24 months, nor did tubulopathy predict clinically relevant eGFR decline.",
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T1 - Low Risk of Proximal Tubular Dysfunction Associated with Emtricitabine-Tenofovir Disoproxil Fumarate Preexposure Prophylaxis in Men and Women

AU - Mugwanya, Kenneth

AU - Baeten, Jared

AU - Celum, Connie

AU - Donnell, Deborah

AU - Nickolas, Thomas

AU - Mugo, Nelly

AU - Branch, Andrea

AU - Tappero, Jordan

AU - Kiarie, James

AU - Ronald, Allan

AU - Yin, Michael

AU - Wyatt, Christina

AU - Baeten, Jared M.

AU - Coombs, Robert W.

AU - Frenkel, Lisa

AU - Hendrix, Craig W.

AU - Lingappa, Jairam R.

AU - McElrath, M. Juliana

AU - Fife, Kenneth

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 - Farquhar, Carey

AU - John-Stewart, Grace

AU - Mugo, Nelly R.

PY - 2016/10/1

Y1 - 2016/10/1

N2 - Objective.Tenofovir disoproxil fumarate (TDF) is associated with proximal tubular dysfunction (tubulopathy) when used in the treatment of human immunodeficiency virus (HIV) infection. We evaluated whether TDF causes tubulopathy when used as HIV preexposure prophylaxis (PrEP) and whether tubulopathy predicts clinically relevant decline (≥25%) in the estimated glomerular filtration rate (eGFR). Methods.A subgroup analysis of the Partners PrEP Study, a randomized, placebo-controlled trial of daily oral TDF, alone or with emtricitabine (FTC), in HIV-uninfected African men and women (Clinicaltrials.gov NCT00557245). Tubulopathy was assessed in concurrently obtained urine and serum samples at the 24-month or last on-treatment visit, predefined as ≥2 of the following: tubular proteinuria, euglycemic glycosuria, increased urinary phosphate, and uric acid excretion. Results.Of 1549 persons studied (776 receiving FTC-TDF, 773 receiving placebo), 64% were male, and the median age was 37 years. Over a median 24 months of study-drug exposure, the frequency of tubulopathy was 1.7% for FTC-TDF versus 1.3% for placebo (odds ratio, 1.30; 95% confidence interval,. 52-3.33; P =. 68); Tubulopathy occurred in 2 of 52 persons (3.8%) with versus 3 of 208 (1.4%) without ≥25% eGFR decline (adjusted odds ratio, 1.39;. 10-14.0; P >. 99). Conclusions.Daily oral FTC-TDF PrEP was not significantly associated with tubulopathy over the course of 24 months, nor did tubulopathy predict clinically relevant eGFR decline.

AB - Objective.Tenofovir disoproxil fumarate (TDF) is associated with proximal tubular dysfunction (tubulopathy) when used in the treatment of human immunodeficiency virus (HIV) infection. We evaluated whether TDF causes tubulopathy when used as HIV preexposure prophylaxis (PrEP) and whether tubulopathy predicts clinically relevant decline (≥25%) in the estimated glomerular filtration rate (eGFR). Methods.A subgroup analysis of the Partners PrEP Study, a randomized, placebo-controlled trial of daily oral TDF, alone or with emtricitabine (FTC), in HIV-uninfected African men and women (Clinicaltrials.gov NCT00557245). Tubulopathy was assessed in concurrently obtained urine and serum samples at the 24-month or last on-treatment visit, predefined as ≥2 of the following: tubular proteinuria, euglycemic glycosuria, increased urinary phosphate, and uric acid excretion. Results.Of 1549 persons studied (776 receiving FTC-TDF, 773 receiving placebo), 64% were male, and the median age was 37 years. Over a median 24 months of study-drug exposure, the frequency of tubulopathy was 1.7% for FTC-TDF versus 1.3% for placebo (odds ratio, 1.30; 95% confidence interval,. 52-3.33; P =. 68); Tubulopathy occurred in 2 of 52 persons (3.8%) with versus 3 of 208 (1.4%) without ≥25% eGFR decline (adjusted odds ratio, 1.39;. 10-14.0; P >. 99). Conclusions.Daily oral FTC-TDF PrEP was not significantly associated with tubulopathy over the course of 24 months, nor did tubulopathy predict clinically relevant eGFR decline.

KW - PrEP

KW - proximal tubular dysfunction

KW - TDF nephrotoxicity

KW - TDF toxicity

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