Renal impairment in a large-scale HIV preexposure prophylaxis implementation cohort

Background: HIV preexposure prophylaxis (PrEP) with fixed-dose tenofovir disoproxil fumarate (TDF) and emtricitabine has been associated with low rates of renal impairment in clinical trials. Large-scale PrEP implementation may result in higher rates, as the prevalence of associated risk factors may be higher than in trial populations. Methods: A posthoc analysis of EPIC-NSW, a large Australian multicentre PrEP implementation trial for patients at high risk of HIV infection. Participants were eligible for inclusion if they commenced PrEP between 1 March 2016 and 30 April 2018, and had renal function assessed at baseline and at least once more before the censor date. The primary outcome was new-onset renal impairment, defined as an estimated glomerular filtration rate (eGFR) Results: A total of 6808 participants were eligible for inclusion. Almost all were male (99%), with a median age of 35 years [interquartile range (IQR): 28-44]. Approximately one-quarter (26%) had a baseline eGFR <90 ml/min per 1.73 m(2). Over a median follow-up period of 1.2 years (IQR: 0.6-1.7), the rate of renal impairment was 5.8 episodes per 1000 person-years [95% confidence interval (CI): 4.0-7.8]. In multivariable Cox regression, there was a higher risk of renal impairment in participants aged >= 50 years [hazard ratio (HR) 14.7, 95% CI: 5.0-43.3, P < 0.001] and those with an eGFR <90 ml/min per 1.73 m(2) (HR 28.9, 95% CI: 6.9-121.9) at baseline. Conclusion: In a large-scale implementation study, TDF-containing PrEP was associated with a low risk of renal impairment overall, whereas older patients and those with preexisting renal dysfunction were at substantially increased risk.