Fanconi syndrome in a patient receiving pre-exposure prophylaxis for HIV infection: case report
Douglas Drak![https://orcid.org/0000-0001-6900-2029](/media/client/orcid_16x16.png)
![https://orcid.org/0000-0003-2660-3558](/media/client/orcid_16x16.png)
A Royal North Shore Hospital, St Leonards, NSW, Australia.
B Faculty of Medicine, Central Clinical School, University of Sydney, Sydney, NSW, Australia.
C Renal Unit, Royal Prince Alfred Hospital, Camperdown, NSW, Australia.
D Holdsworth House Medical Practice, College Street, Sydney, NSW, Australia.
Sexual Health 19(3) 224-227 https://doi.org/10.1071/SH21185
Submitted: 24 September 2021 Accepted: 4 May 2022 Published: 26 May 2022
© 2022 The Author(s) (or their employer(s)). Published by CSIRO Publishing
Abstract
Background: Tenofovir disoproxil is efficacious in the preventing HIV infection as part of a pre-exposure prophylaxis (PrEP) regimen. Although its use has been associated with impaired renal function, instances of Fanconi syndrome are extremely rare. This may change with increased uptake of PrEP.
Methods: A 55-year-old male patient (he/him/his) was commenced on PrEP with a baseline estimated glomerular filtration rate (eGFR) of approximately 60 mL/min/1.73 m2.
Results: Within 6 months, he developed new and worsening proteinuria, glycosuria and aminoaciduria despite no apparent change in eGFR. PrEP was discontinued and his urinary abnormalities rapidly resolved. The patient remains off PrEP.
Conclusions: Fanconi syndrome is a rare, but known complication of tenofovir disoproxil. This is the first report related to PrEP in Australia. While tenofovir associated nephrotoxicity in patients taking PrEP is uncommon, the patient’s age and pre-existing renal impairment placed him at substantially higher risk. At-risk patients need more frequent monitoring of their eGFR and proteinuria. Urinary protein to creatinine ratio is the preferred to dipstick testing for proteinuria and the latter does not readily detect the low molecular wight proteinuria characteristic of tenofovir toxicity. Early recognition of these patients is essential, as prompt cessation of PrEP can often reverse renal abnormalities.
Keywords: emtricitabine, estimated glomerular filtration rate, Fanconi syndrome, HIV prevention, pre-exposure prophylaxis, PrEP, risk reduction, tenofovir disoproxil.
References
[1] Grulich AE, Guy R, Amin J, Jin F, Selvey C, Holden J, et al. Population-level effectiveness of rapid, targeted, high-coverage roll-out of HIV pre-exposure prophylaxis in men who have sex with men: the EPIC-NSW prospective cohort study. Lancet HIV 2018; 5 e629–37.| Population-level effectiveness of rapid, targeted, high-coverage roll-out of HIV pre-exposure prophylaxis in men who have sex with men: the EPIC-NSW prospective cohort study.Crossref | GoogleScholarGoogle Scholar | 30343026PubMed |
[2] Hall AM, Hendry BM, Nitsch D, Connolly JO. Tenofovir-associated kidney toxicity in HIV-infected patients: a review of the evidence. Am J Kidney Dis 2011; 57 773–80.
| Tenofovir-associated kidney toxicity in HIV-infected patients: a review of the evidence.Crossref | GoogleScholarGoogle Scholar | 21435764PubMed |
[3] Van Rompay KKA, Durand-Gasselin L, Brignolo LL, Ray AS, Abel K, Cihlar T, et al. Chronic administration of tenofovir to rhesus macaques from infancy through adulthood and pregnancy: summary of pharmacokinetics and biological and virological effects. Antimicrob Agents Chemother 2008; 52 3144–60.
| Chronic administration of tenofovir to rhesus macaques from infancy through adulthood and pregnancy: summary of pharmacokinetics and biological and virological effects.Crossref | GoogleScholarGoogle Scholar |
[4] Drak D, McManus H, Vickers T, Heron JE, Vaccher S, Zablotska I, et al. Renal impairment in a large-scale HIV pre-exposure prophylaxis implementation cohort. AIDS 2021; 35 2319–26.
| Renal impairment in a large-scale HIV pre-exposure prophylaxis implementation cohort.Crossref | GoogleScholarGoogle Scholar | 34310371PubMed |
[5] Gandhi M, Glidden DV, Mayer K, Schechter M, Buchbinder S, Grinsztejn B, et al. Association of age, baseline kidney function, and medication exposure with declines in creatinine clearance on pre-exposure prophylaxis: an observational cohort study. Lancet HIV 2016; 3 e521–8.
| Association of age, baseline kidney function, and medication exposure with declines in creatinine clearance on pre-exposure prophylaxis: an observational cohort study.Crossref | GoogleScholarGoogle Scholar | 27658870PubMed |
[6] Marcus JL, Hurley LB, Hare CB, Nguyen DP, Phengrasamy T, Silverberg MJ, et al. Preexposure prophylaxis for hiv prevention in a large integrated health care system: adherence, renal safety, and discontinuation. J Acquir Immune Defic Syndr 2016; 73 540–6.
| Preexposure prophylaxis for hiv prevention in a large integrated health care system: adherence, renal safety, and discontinuation.Crossref | GoogleScholarGoogle Scholar | 27851714PubMed |
[7] Kirby Institute. Monitoring HIV pre-exposure prophylaxis (PrEP) uptake in Australia (Issue4). Sydney: Kirby Institute, UNSW Sydney; 2021.
[8] The Australasian Society of HIV and Sexual Health Medicine (ASHM). PrEP guidelines update. Prevent HIV by prescribing PrEP. Sydney; 2019. Available at https://www.ashm.org.au/resources/hiv-resources-list/prep-guidelines-2019/
[9] Mugwanya KK, Wyatt C, Celum C, Donnell D, Kiarie J, Ronald A, et al. Reversibility of glomerular renal function decline in HIV-uninfected men and women discontinuing emtricitabine-tenofovir disoproxil fumarate pre-exposure prophylaxis. J Acquir Immune Defic Syndr 2016; 71 374–80.
| Reversibility of glomerular renal function decline in HIV-uninfected men and women discontinuing emtricitabine-tenofovir disoproxil fumarate pre-exposure prophylaxis.Crossref | GoogleScholarGoogle Scholar | 26914909PubMed |
[10] Jose S, Hamzah L, Campbell LJ, Hill T, Fisher M, Leen C, et al. Incomplete reversibility of estimated glomerular filtration rate decline following tenofovir disoproxil fumarate exposure. J Infect Dis 2014; 210 363–73.
| Incomplete reversibility of estimated glomerular filtration rate decline following tenofovir disoproxil fumarate exposure.Crossref | GoogleScholarGoogle Scholar | 24585896PubMed |
[11] Khan S, Funk CA, Corado K, Morris S, Dube MP. Tenofovir disoproxil fumarate-associated fanconi syndrome in an human immunodeficiency virus (HIV)-uninfected man receiving HIV pre-exposure prophylaxis. Open Forum Infect Dis 2017; 4 ofx149
| Tenofovir disoproxil fumarate-associated fanconi syndrome in an human immunodeficiency virus (HIV)-uninfected man receiving HIV pre-exposure prophylaxis.Crossref | GoogleScholarGoogle Scholar | 30591921PubMed |
[12] Mayer KH, Molina J-M, Thompson MA, Anderson PL, Mounzer KC, De Wet JJ, et al. Emtricitabine and tenofovir alafenamide vs emtricitabine and tenofovir disoproxil fumarate for HIV pre-exposure prophylaxis (DISCOVER): primary results from a randomised, double-blind, multicentre, active-controlled, phase 3, non-inferiority trial. Lancet 2020; 396 239–54.
| Emtricitabine and tenofovir alafenamide vs emtricitabine and tenofovir disoproxil fumarate for HIV pre-exposure prophylaxis (DISCOVER): primary results from a randomised, double-blind, multicentre, active-controlled, phase 3, non-inferiority trial.Crossref | GoogleScholarGoogle Scholar | 32711800PubMed |
[13] Liegeon G, Antoni G, Pialoux G, Capitant C, Cotte L, Charreau I, et al. Changes in kidney function among men having sex with men starting on demand tenofovir disoproxil fumarate – emtricitabine for HIV pre-exposure prophylaxis. Journal of the International AIDS Society 2020; 23 e25420
| Changes in kidney function among men having sex with men starting on demand tenofovir disoproxil fumarate – emtricitabine for HIV pre-exposure prophylaxis.Crossref | GoogleScholarGoogle Scholar | 32086878PubMed |
[14] Gandhi M, Murnane PM, Bacchetti P, Elion R, Kolber MA, Cohen SE, et al. Hair levels of preexposure prophylaxis drugs measure adherence and are associated with renal decline among men/transwomen. AIDS 2017; 31 2245–51.
| Hair levels of preexposure prophylaxis drugs measure adherence and are associated with renal decline among men/transwomen.Crossref | GoogleScholarGoogle Scholar | 28832411PubMed |
[15] The Euopean Aids Clinical Society. Guidelines Version 10.0; 2019. Available at https://www.eacsociety.org/media/guidelines-10.1_30032021_1.pdf
[16] Ando M, Yanagisawa N, Ajisawa A, Tsuchiya K, Nitta K. Urinary albumin excretion within the normal range is an independent risk for near-term development of kidney disease in HIV-infected patients. Nephrol Dial Transplant 2011; 26 3923–9.
| Urinary albumin excretion within the normal range is an independent risk for near-term development of kidney disease in HIV-infected patients.Crossref | GoogleScholarGoogle Scholar | 21427068PubMed |
[17] Grigsby IF, Pham L, Mansky LM, Gopalakrishnan R, Mansky KC. Tenofovir-associated bone density loss. Ther Clin Risk Manag 2010; 6 41–7.
| 20169035PubMed |
[18] Gallant JE, Daar ES, Raffi F, Brinson C, Ruane P, DeJesus E, et al. Efficacy and safety of tenofovir alafenamide versus tenofovir disoproxil fumarate given as fixed-dose combinations containing emtricitabine as backbones for treatment of HIV-1 infection in virologically suppressed adults: a randomised, double-blind, active-controlled phase 3 trial. Lancet HIV 2016; 3 e158–65.
| Efficacy and safety of tenofovir alafenamide versus tenofovir disoproxil fumarate given as fixed-dose combinations containing emtricitabine as backbones for treatment of HIV-1 infection in virologically suppressed adults: a randomised, double-blind, active-controlled phase 3 trial.Crossref | GoogleScholarGoogle Scholar | 27036991PubMed |
[19] Mills A, Arribas JR, Andrade-Villanueva J, DiPerri G, Van Lunzen J, Koenig E, et al. Switching from tenofovir disoproxil fumarate to tenofovir alafenamide in antiretroviral regimens for virologically suppressed adults with HIV-1 infection: a randomised, active-controlled, multicentre, open-label, phase 3, non-inferiority study. Lancet Infect Dis 2016; 16 43–52.
| Switching from tenofovir disoproxil fumarate to tenofovir alafenamide in antiretroviral regimens for virologically suppressed adults with HIV-1 infection: a randomised, active-controlled, multicentre, open-label, phase 3, non-inferiority study.Crossref | GoogleScholarGoogle Scholar | 26538525PubMed |
[20] Mothobi NZ, Masters J, Marriott DJ. Fanconi syndrome due to tenofovir disoproxil fumarate reversed by switching to tenofovir alafenamide fumarate in an HIV-infected patient. Ther Adv Infect Dis 2018; 5 91–5.
| Fanconi syndrome due to tenofovir disoproxil fumarate reversed by switching to tenofovir alafenamide fumarate in an HIV-infected patient.Crossref | GoogleScholarGoogle Scholar | 30224952PubMed |