Commencing pre-exposure prophylaxis can lead to a small rapid decline in kidney function, but this effect is reversible, according to Sydney researchers
Fixed-dose combination tenofovir disoproxil fumarate (TDF) and emtricitabine (FTC) for pre-exposure prophylaxis (PrEP) has been found to be highly efficacious in HIV prevention, say researchers from the University of Sydney and the University of New South Wales.
This treatment combination has been found to reduce risk of HIV acquisition by 86%.
However TDF has also be associated with a number of adverse events, with nephrotoxicity of particular concern, they write in an article published this month in PLOS One.
Nephrotoxicity first manifests as proteinuria, followed by a progressive decline in estimated glomerular filtration rate (eGFR).
Researchers conducted a retrospective review of all PrEP patients commenced on TDF/FTC at an inner metropolitan sexual health clinic in Sydney between April 2016 and July 2017, with follow-up data obtained at three-monthly intervals until 18 months.
Of a total 525 patients, 99 (19%, 95%CI: 16-22) had a baseline eGFR under 90, but greater than 60mL/min/1.73m2.
Patients were excluded from the study if their baseline eGFR was <60mL/min/1.73m2.
Approximately one-fifth of patients were lost to follow-up, having missed two or more consecutive appointments, and may have permanently discontinued PrEP.
However the authors say there is nothing to suggest renal function in this subgroup would differ substantially from those who remained in the study or discounted PrEP for documented reasons.
Patients were found to have reduced eGFR compared to baseline through the duration of the study.
This was statistically significant at all time points (p<0.05) and borderline significant at 15 months (p=0.056).
The majority of this decline occurred between PrEP commencement and the first follow-up at three months.
However, there was a more gradual reduction in eGFR across the subsequent follow-up periods.
This decline began to reverse subsequently, however, despite continued PrEP use.
Individual test results showing significant renal impairments was common, with nearly one-fifth of patients (n=98, 95%CI: 15-22) meeting one of the three criteria for an abnormal eGFR.
Proteinuria was identified in 64 patients (12.2%, 95%CI: 9.4-15.0).
TDF/FTC containing PrEP was associated with a small persistent decrease in eGFR, although cessation of PrEP due to severe renal impairment was rare.
Substantial renal impairment was more common in patients over 40 years of age.
The researchers say these findings support those of previous clinical trials and observational studies.
Potential for long-term eGFR decline in PrEP patients is as yet unclear, they say, due to a “paucity” of long-term data, adding that this is an important focus for future study.
Current PrEP guidelines recommend that eGFR be tested three-monthly. Routine monitoring of renal function is critical in patients receiving TDF, say the researchers, in order to detect and treat renal dysfunction.
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