Kenneth Mugwanya1, Jared Baeten2, Connie Celum2, Deborah Donnell3, Thomas Nickolas4, Nelly Mugo5, Andrea Branch6, Jordan Tappero7, James Kiarie8, Allan Ronald9, Michael Yin10, Christina Wyatt11. 1. Department of Epidemiology Department of Global Health Division of Disease Control, School of Public Health, Makerere University, Kampala, Uganda. 2. Department of Epidemiology Department of Global Health Department of Medicine, University of Washington. 3. Department of Vaccine and Infectious Disease Division, Fred Hutchinson Cancer Research Center, Seattle, Washington. 4. Department of Medicine, Division of Nephrology. 5. Department of Global Health Kenya Medical Research Institute. 6. Department of Medicine, Division of Liver Diseases. 7. Division of Global Health Protection, Center for Global Health, Centers for Disease Control and Prevention, Atlanta, Georgia. 8. Department of Obstetrics and Gynecology, University of Nairobi, Kenya. 9. Department of Medicine, University of Manitoba, Winnipeg, Canada. 10. Department of Medicine, Division of Infectious Diseases, Columbia University Medical Center. 11. Department of Medicine, Division of Nephrology, Icahn School of Medicine at Mount Sinai, New York, New York.
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.
RCT Entities:
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.
Authors: Sonia Rodríguez-Nóvoa; Pablo Labarga; Antonio D'avolio; Pablo Barreiro; Marta Albalate; Eugenia Vispo; Carmen Solera; Marco Siccardi; Stefano Bonora; Giovanni Di Perri; Vincent Soriano Journal: AIDS Date: 2010-04-24 Impact factor: 4.177
Authors: Michael C Thigpen; Poloko M Kebaabetswe; Lynn A Paxton; Dawn K Smith; Charles E Rose; Tebogo M Segolodi; Faith L Henderson; Sonal R Pathak; Fatma A Soud; Kata L Chillag; Rodreck Mutanhaurwa; Lovemore Ian Chirwa; Michael Kasonde; Daniel Abebe; Evans Buliva; Roman J Gvetadze; Sandra Johnson; Thom Sukalac; Vasavi T Thomas; Clyde Hart; Jeffrey A Johnson; C Kevin Malotte; Craig W Hendrix; John T Brooks Journal: N Engl J Med Date: 2012-07-11 Impact factor: 91.245
Authors: Jared M Baeten; Deborah Donnell; Patrick Ndase; Nelly R Mugo; James D Campbell; Jonathan Wangisi; Jordan W Tappero; Elizabeth A Bukusi; Craig R Cohen; Elly Katabira; Allan Ronald; Elioda Tumwesigye; Edwin Were; Kenneth H Fife; James Kiarie; Carey Farquhar; Grace John-Stewart; Aloysious Kakia; Josephine Odoyo; Akasiima Mucunguzi; Edith Nakku-Joloba; Rogers Twesigye; Kenneth Ngure; Cosmas Apaka; Harrison Tamooh; Fridah Gabona; Andrew Mujugira; Dana Panteleeff; Katherine K Thomas; Lara Kidoguchi; Meighan Krows; Jennifer Revall; Susan Morrison; Harald Haugen; Mira Emmanuel-Ogier; Lisa Ondrejcek; Robert W Coombs; Lisa Frenkel; Craig Hendrix; Namandjé N Bumpus; David Bangsberg; Jessica E Haberer; Wendy S Stevens; Jairam R Lingappa; Connie Celum Journal: N Engl J Med Date: 2012-07-11 Impact factor: 91.245
Authors: Michael Horberg; Beth Tang; William Towner; Michael Silverberg; Susan Bersoff-Matcha; Leo Hurley; Joseph Chang; Jackie Blank; Charles Quesenberry; Daniel Klein Journal: J Acquir Immune Defic Syndr Date: 2010-01 Impact factor: 3.731
Authors: Pablo Labarga; Pablo Barreiro; Luz Martin-Carbonero; Sonia Rodriguez-Novoa; Carmen Solera; Jose Medrano; Pablo Rivas; Marta Albalater; Francisco Blanco; Victoria Moreno; Eugenia Vispo; Vincent Soriano Journal: AIDS Date: 2009-03-27 Impact factor: 4.177
Authors: Andrew S Levey; Lesley A Stevens; Christopher H Schmid; Yaping Lucy Zhang; Alejandro F Castro; Harold I Feldman; John W Kusek; Paul Eggers; Frederick Van Lente; Tom Greene; Josef Coresh Journal: Ann Intern Med Date: 2009-05-05 Impact factor: 25.391
Authors: Kenneth K Mugwanya; Jared M Baeten; Christina Wyatt; Nelly R Mugo; Connie L Celum; Allan Ronald; John Kiarie; Elly Katabira; Renee Heffron Journal: J Acquir Immune Defic Syndr Date: 2018-02-01 Impact factor: 3.731
Authors: Vasantha Jotwani; Rebecca Scherzer; David V Glidden; Megha Mehrotra; Patricia Defechereux; Albert Liu; Monica Gandhi; Michael Bennett; Steven G Coca; Chirag R Parikh; Robert M Grant; Michael G Shlipak Journal: J Acquir Immune Defic Syndr Date: 2018-06-01 Impact factor: 3.731
Authors: Thomas L Nickolas; Jonathan Barasch; Kenneth K Mugwanya; Andrea D Branch; Renee Heffron; Valentine Wanga; Nelly R Mugo; Allan Ronald; Connie Celum; Deborah Donnell; Jared M Baeten; Christina M Wyatt Journal: AIDS Date: 2021-06-01 Impact factor: 4.632
Authors: Simon B Ascher; Rebecca Scherzer; Michelle M Estrella; Judy Shigenaga; Kimberly A Spaulding; David V Glidden; Megha L Mehrotra; Patricia Defechereux; Monica Gandhi; Robert M Grant; Michael G Shlipak; Vasantha Jotwani Journal: AIDS Date: 2020-04-01 Impact factor: 4.632