Age over 50 years and pre-existing kidney function are the risk factors for the emergence of renal dysfunction while taking PrEP, according to data from an Australian PrEP demonstration study by researchers at the University of New South Wales, the University of Sydney and the Holdsworth House Medical Practice, Sydney, Australia, presented to the recent Conference on Retroviruses and Opportunistic Infections (CROI 2020). Aidsmap reports that the study is important because it provides “real-world” information about the rate and risk factors for renal decline among people taking PrEP. Approximately 2% of study participants developed renal dysfunction over two years of follow-up but rates differed according to age and kidney function at the start of the study.
The research provides reassurance that long-term PrEP does not cause high rates of renal dysfunction and also helps individuals who would especially benefit from close monitoring of kidney health while taking the therapy.
Treatment with the antiretroviral drugs tenofovir/emtricitabine PrEP is a very effective way of preventing infection with HIV. Both drugs have a good safety and side-effect profile. However, it has long been recognised that therapy with tenofovir can cause declines in kidney function.
Clinical trials into the safety and effectiveness of tenofovir-based PrEP found a very low incidence of renal impairment. A team of investigators led by Dr Hamish McManus of the Kirby Institute examined data from the New South Wales PrEP demonstration trial (EPIC-NSW) to see if this was also the case when tenofovir-containing PrEP was routinely used in real-world settings.
“In a large real-world PrEP cohort, risk of renal impairment increased over two years of PrEP, with older patients and those with pre-existing renal dysfunction at significantly higher risk,” conclude McManus and colleagues.
Abstract
Co-formulated tenofovir disoproxil fumarate/emtricitabine is prescribed as pre-exposure prophylaxis (PrEP) to prevent HIV infection. Prior studies have found low incidence of new renal impairment in people taking PrEP but have been restricted to clinical trial settings. We sought to quantify rates of renal impairment in a large prospective cohort of participants taking PrEP as part of a population-level implementation study in Australia.
Participants enrolled in the EPIC-NSW study with baseline eGFR≥60 ml/min/1.73m2, more than one PrEP dispensing visit between 1 March 2016 and 30 April 2018, and no recorded history of prior PrEP were included. Patients without eGFR monitoring during this period were excluded. Risk of renal impairment (defined as average eGFR of two consecutive tests <60) was estimated using the Kaplan-Meier method. Cox proportional hazards models stratified by study site were used to compare risk factors including baseline eGFR (60-90, ≥90), age (<40, 40-49, ≥50), sex, recreational drug use, and HBV and HCV infection status. Time-updated PrEP medication possession ratio (MPR) was included as a binary independent covariate (<0.95, ≥0.95). Significant covariates (p<0.05) were included in a multivariate model.
Of 9,596 participants dispensed PrEP, 4,514 met the inclusion criteria for this analysis. Most were aged <50 (88%), male (99%), and had baseline eGFR 90 (76%). Baseline eGFR<90 was observed in 55% of participants aged 50 compared to 20% aged <50 (p<0.001). The observed rate of renal impairment was 8.0/1,000 person-years (95%CI: 5.86-10.99) over 4,859 person-years follow-up, with two-year cumulative risk of 1.7% (95%CI: 1.11-2.70) (Figure 1). Renal impairment was highest in patients aged 50 at 44.7/1,000 person-years (95%CI: 30.65-65.16) and two-year cumulative risk of 8.3% (95%CI: 5.35-12.69). The rate of renal impairment was also increased in participants with baseline eGFR<90 (32.0/1,000 person-years [95%CI: 23.20-44.20]) and with MPR0.95 (11.2/1,000 person-years, [95%CI: 7.95-15.72]). A multivariate model showed increased risk associated with age 50 compared to <40 (HR: 12.9 [95%CI: 4.31-38.58], p<0.001) and baseline eGFR <90 (HR: 25.6 [95%CI: 5.99-109.18], p<0.001) after adjustment for MPR (HR: 2.3 [95%CI: 0.96-5.68], p=0.060).
In a large real-world PrEP cohort, risk of renal impairment increased over two years of PrEP, with older patients and those with pre-existing renal dysfunction at significantly higher risk.
Authors
Hamish McManus, Douglas Drak, Jack E Heron, Tobias Vickers, Stefanie Vaccher, Iryna Zablotska, Rebecca J Guy, Benjamin Bavinton, Fengyi Jin
[link url="http://www.aidsmap.com/news/mar-2020/older-age-and-baseline-kidney-function-are-key-risk-factors-renal-dysfunction-while"]Full Aidsmap report[/link]
[link url="http://www.croiconference.org/sessions/renal-impairment-preexposure-prophylaxis-implementation-cohort-australia"]CROI 2020 abstract[/link]