Renal impairment associated with tenofovir disoproxil fumarate for antiretroviral therapy and HIV pre-exposure prophylaxis: An observational cohort study.

<h4>Background</h4>Tenofovir disoproxil fumarate (TDF) is associated with adverse renal outcomes when prescribed for HIV infection. There are few data concerning real-world renal outcomes amongst patients prescribed TDF for pre-exposure prophylaxis (PrEP).<h4>Methods and findings&l...

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Main Authors: Jack E Heron, Hamish McManus, Tobias Vickers, Kathleen Ryan, Edwina Wright, Allison Carter, Mark Stoove, Jason Asselin, Andrew Grulich, Basil Donovan, Rebecca Guy, Rick Varma, Marcus Chen, Nathan Ryder, David A Lewis, David J Templeton, Catherine C O'Connor, David M Gracey, ACCESS Collaboration
Format: Article
Language:English
Published: Public Library of Science (PLoS) 2023-01-01
Series:PLoS ONE
Online Access:https://doi.org/10.1371/journal.pone.0280339
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author Jack E Heron
Hamish McManus
Tobias Vickers
Kathleen Ryan
Edwina Wright
Allison Carter
Mark Stoove
Jason Asselin
Andrew Grulich
Basil Donovan
Rebecca Guy
Rick Varma
Marcus Chen
Nathan Ryder
David A Lewis
David J Templeton
Catherine C O'Connor
David M Gracey
ACCESS Collaboration
author_facet Jack E Heron
Hamish McManus
Tobias Vickers
Kathleen Ryan
Edwina Wright
Allison Carter
Mark Stoove
Jason Asselin
Andrew Grulich
Basil Donovan
Rebecca Guy
Rick Varma
Marcus Chen
Nathan Ryder
David A Lewis
David J Templeton
Catherine C O'Connor
David M Gracey
ACCESS Collaboration
author_sort Jack E Heron
collection DOAJ
description <h4>Background</h4>Tenofovir disoproxil fumarate (TDF) is associated with adverse renal outcomes when prescribed for HIV infection. There are few data concerning real-world renal outcomes amongst patients prescribed TDF for pre-exposure prophylaxis (PrEP).<h4>Methods and findings</h4>Data were extracted from 52 sexual health clinics across Australia from 2009-2019. All patients prescribed TDF-containing antiretroviral therapy and PrEP were included. Rates of renal impairment (a fall in eGFR to <60 ml/min/1·73m2) were calculated for people living with HIV (PLWHIV) prescribed TDF and HIV negative PrEP-users. Risk factors were assessed using Cox-proportional hazards models. Sensitivity analysis of risk using 1:1 propensity-score matching to adjust for potential imbalance in HIV and PrEP cohorts was conducted. 5,973 patients on PrEP and 1,973 PLWHIV were included. There were 39 (0.7%) instances of renal impairment in the PrEP group and 81 (4.1%) in the PLWHIV cohort (hazard ratio [HR]:0.35 95% confidence interval [CI]: 0.22-0.56). Rates of renal impairment were 4.01/1000 person-years (95%CI:2.93-5.48) in the PrEP cohort and 16.18/1000 person-years (95%CI:13.01-20.11) in the PLWHIV cohort (p<0.001). Predictors of renal impairment were: older age (40-49 years (HR:5.09 95%CI: 2.12-12.17) and 50-82 years (HR:13.69 95%CI: 5.92-31.67) (compared with 30-39 years) and baseline eGFR<90ml/min (HR:61.19 95%CI: 19.27-194.30). After adjusting for age and baseline eGFR the rate of renal impairment remained lower in the PrEP cohort (aHR:0.62 95%CI: 0.40-0.94, p = 0.023). In propensity-matched analysis using 1,622 patients per cohort the risk of renal impairment remained higher in the PLWHIV cohort (log-rank p = 0.001).<h4>Conclusion</h4>Patients prescribed TDF-based PrEP had lower rates of renal impairment than patients prescribed TDF for HIV infection. In propensity analysis, after matching for some risk factors, rates of renal impairment remained higher amongst patients with HIV.
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spelling doaj.art-4521ee89fb3946b4b84878b76f901cae2023-03-02T05:31:53ZengPublic Library of Science (PLoS)PLoS ONE1932-62032023-01-01182e028033910.1371/journal.pone.0280339Renal impairment associated with tenofovir disoproxil fumarate for antiretroviral therapy and HIV pre-exposure prophylaxis: An observational cohort study.Jack E HeronHamish McManusTobias VickersKathleen RyanEdwina WrightAllison CarterMark StooveJason AsselinAndrew GrulichBasil DonovanRebecca GuyRick VarmaMarcus ChenNathan RyderDavid A LewisDavid J TempletonCatherine C O'ConnorDavid M GraceyACCESS Collaboration<h4>Background</h4>Tenofovir disoproxil fumarate (TDF) is associated with adverse renal outcomes when prescribed for HIV infection. There are few data concerning real-world renal outcomes amongst patients prescribed TDF for pre-exposure prophylaxis (PrEP).<h4>Methods and findings</h4>Data were extracted from 52 sexual health clinics across Australia from 2009-2019. All patients prescribed TDF-containing antiretroviral therapy and PrEP were included. Rates of renal impairment (a fall in eGFR to <60 ml/min/1·73m2) were calculated for people living with HIV (PLWHIV) prescribed TDF and HIV negative PrEP-users. Risk factors were assessed using Cox-proportional hazards models. Sensitivity analysis of risk using 1:1 propensity-score matching to adjust for potential imbalance in HIV and PrEP cohorts was conducted. 5,973 patients on PrEP and 1,973 PLWHIV were included. There were 39 (0.7%) instances of renal impairment in the PrEP group and 81 (4.1%) in the PLWHIV cohort (hazard ratio [HR]:0.35 95% confidence interval [CI]: 0.22-0.56). Rates of renal impairment were 4.01/1000 person-years (95%CI:2.93-5.48) in the PrEP cohort and 16.18/1000 person-years (95%CI:13.01-20.11) in the PLWHIV cohort (p<0.001). Predictors of renal impairment were: older age (40-49 years (HR:5.09 95%CI: 2.12-12.17) and 50-82 years (HR:13.69 95%CI: 5.92-31.67) (compared with 30-39 years) and baseline eGFR<90ml/min (HR:61.19 95%CI: 19.27-194.30). After adjusting for age and baseline eGFR the rate of renal impairment remained lower in the PrEP cohort (aHR:0.62 95%CI: 0.40-0.94, p = 0.023). In propensity-matched analysis using 1,622 patients per cohort the risk of renal impairment remained higher in the PLWHIV cohort (log-rank p = 0.001).<h4>Conclusion</h4>Patients prescribed TDF-based PrEP had lower rates of renal impairment than patients prescribed TDF for HIV infection. In propensity analysis, after matching for some risk factors, rates of renal impairment remained higher amongst patients with HIV.https://doi.org/10.1371/journal.pone.0280339
spellingShingle Jack E Heron
Hamish McManus
Tobias Vickers
Kathleen Ryan
Edwina Wright
Allison Carter
Mark Stoove
Jason Asselin
Andrew Grulich
Basil Donovan
Rebecca Guy
Rick Varma
Marcus Chen
Nathan Ryder
David A Lewis
David J Templeton
Catherine C O'Connor
David M Gracey
ACCESS Collaboration
Renal impairment associated with tenofovir disoproxil fumarate for antiretroviral therapy and HIV pre-exposure prophylaxis: An observational cohort study.
PLoS ONE
title Renal impairment associated with tenofovir disoproxil fumarate for antiretroviral therapy and HIV pre-exposure prophylaxis: An observational cohort study.
title_full Renal impairment associated with tenofovir disoproxil fumarate for antiretroviral therapy and HIV pre-exposure prophylaxis: An observational cohort study.
title_fullStr Renal impairment associated with tenofovir disoproxil fumarate for antiretroviral therapy and HIV pre-exposure prophylaxis: An observational cohort study.
title_full_unstemmed Renal impairment associated with tenofovir disoproxil fumarate for antiretroviral therapy and HIV pre-exposure prophylaxis: An observational cohort study.
title_short Renal impairment associated with tenofovir disoproxil fumarate for antiretroviral therapy and HIV pre-exposure prophylaxis: An observational cohort study.
title_sort renal impairment associated with tenofovir disoproxil fumarate for antiretroviral therapy and hiv pre exposure prophylaxis an observational cohort study
url https://doi.org/10.1371/journal.pone.0280339
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