Observational Study

. 2023 Feb 24;18(2):e0280339.

doi: 10.1371/journal.pone.0280339. eCollection 2023.

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

Jack E Heron^{1

2}, Hamish McManus³, Tobias Vickers³, Kathleen Ryan^{4

5}, Edwina Wright^{4

5

6}, Allison Carter³, Mark Stoove⁵, Jason Asselin⁵, Andrew Grulich³, Basil Donovan³, Rebecca Guy³, Rick Varma^{3

7}, Marcus Chen^{8

9}, Nathan Ryder^{3

10

11}, David A Lewis^{12

13

14}, David J Templeton^{15

16}, Catherine C O'Connor³, David M Gracey^{1

15}; ACCESS Collaboration

Affiliations

¹ Department of Renal Medicine, Royal Prince Alfred Hospital, Camperdown, New South Wales, Australia.
² Department of Medicine, Albury Wodonga Health, Wodonga, Victoria, Australia.
³ The Kirby Institute, University of New South Wales, Kensington, New South Wales, Australia.
⁴ Department of Infectious Disease, Alfred Health, Melbourne, Victoria, Australia.
⁵ Burnet Institute, Melbourne, Victoria, Australia.
⁶ Peter Doherty Institute, Melbourne, Victoria, Australia.
⁷ Sydney Sexual Health Centre, Sydney Hospital, Sydney, New South Wales, Australia.
⁸ Melbourne Sexual Health Centre, Alfred Health, Melbourne, Victoria, Australia.
⁹ Central Clinical School, Monash University, Melbourne, Victoria, Australia.
¹⁰ Hunter New England Clinic, Tamworth, New South Wales, Australia.
¹¹ School of Medicine and Public Health, University of Newcastle, Callaghan, New South Wales, Australia.
¹² Western Sydney Sexual Health Centre, Western Sydney Local Health District, Parramatta, New South Wales, Australia.
¹³ Faculty of Medicine and Health, Westmead Clinical School, University of Sydney, Westmead, New South Wales, Australia.
¹⁴ Marie Bashir Institute for Infectious Diseases and Biosecurity, University of Sydney, Westmead, New South Wales, Australia.
¹⁵ Faculty of Medicine and Health, University of Sydney, Camperdown, New South Wales, Australia.
¹⁶ Department of Sexual Health Medicine and Sexual Assault Medical Service, Sydney Local Health District, Sydney, New South Wales, Australia.

PMID: 36827395
PMCID: PMC9955644
DOI: 10.1371/journal.pone.0280339

Observational Study

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

Jack E Heron et al. PLoS One. 2023.

. 2023 Feb 24;18(2):e0280339.

doi: 10.1371/journal.pone.0280339. eCollection 2023.

Authors

Affiliations

¹ Department of Renal Medicine, Royal Prince Alfred Hospital, Camperdown, New South Wales, Australia.
² Department of Medicine, Albury Wodonga Health, Wodonga, Victoria, Australia.
³ The Kirby Institute, University of New South Wales, Kensington, New South Wales, Australia.
⁴ Department of Infectious Disease, Alfred Health, Melbourne, Victoria, Australia.
⁵ Burnet Institute, Melbourne, Victoria, Australia.
⁶ Peter Doherty Institute, Melbourne, Victoria, Australia.
⁷ Sydney Sexual Health Centre, Sydney Hospital, Sydney, New South Wales, Australia.
⁸ Melbourne Sexual Health Centre, Alfred Health, Melbourne, Victoria, Australia.
⁹ Central Clinical School, Monash University, Melbourne, Victoria, Australia.
¹⁰ Hunter New England Clinic, Tamworth, New South Wales, Australia.
¹¹ School of Medicine and Public Health, University of Newcastle, Callaghan, New South Wales, Australia.
¹² Western Sydney Sexual Health Centre, Western Sydney Local Health District, Parramatta, New South Wales, Australia.
¹³ Faculty of Medicine and Health, Westmead Clinical School, University of Sydney, Westmead, New South Wales, Australia.
¹⁴ Marie Bashir Institute for Infectious Diseases and Biosecurity, University of Sydney, Westmead, New South Wales, Australia.
¹⁵ Faculty of Medicine and Health, University of Sydney, Camperdown, New South Wales, Australia.
¹⁶ Department of Sexual Health Medicine and Sexual Assault Medical Service, Sydney Local Health District, Sydney, New South Wales, Australia.

PMID: 36827395
PMCID: PMC9955644
DOI: 10.1371/journal.pone.0280339

Abstract

Background: 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).

Methods and findings: 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).

Conclusion: 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.

Copyright: © 2023 Heron et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

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Conflict of interest statement

The authors have declared that no competing interests exist.

Figures

**Fig 1**
Text: Kaplan-Meier failure curves for time to sustained renal failure for PLWHIV receiving antiretroviral therapy compared to HIV negative participants receiving PrEP before (Panel A) and after (Panel B) propensity score matching).

See this image and copyright information in PMC

References

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

Affiliations

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

Authors

Affiliations

Abstract

Conflict of interest statement

Figures

References

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LinkOut - more resources

Full Text Sources

Medical

Research Materials

Miscellaneous