by Carolyn Chu, MD, MSc, AAHIVS, AAHIVM Chief Medical Officer

October 11, 2022

Featured Literature:
Liegeon G, Assoumou L, Ghosn J, et al.  Impact on renal function of daily and on-demand HIV pre-exposure prophylaxis in the ANRS-PREVENIR study.  J Antimicrob Chemother.  2022 Oct 7:dkac336.  doi:10.1093/jac/dkac336.  PMID 36205009.  

This study examined whether a reduction of exposure to tenofovir disoproxil as on-demand PrEP was associated with improved renal safety.  Investigators classified participants into people who: (a) reported daily PrEP use at ≥ 75% of visits (n = 499); (b) reported on-demand use at ≥ 75% of visits (n = 494); and (c) reported alternating between on-demand and daily use and did not meet criteria for other classification (n = 260).  Median baseline eGFR was 104 mL/min/1.73m2 and 43% had baseline risk factors of kidney dysfunction, i.e., age > 40 years and/or baseline eGFR < 90 mL/min/1.73m2.  After 22.3 months mean follow-up time, mean AUC of the ΔeGFR was -1.09 in the daily PrEP group, -0.69 in the switches group, and +0.18 in the on-demand group.  Compared to daily PrEP, AUC of the ΔeGFR was significantly higher in the on-demand group (this persisted after adjusting for baseline age and eGFR).  In participants with baseline risk factors of kidney dysfunction, adjusted mean AUC of ΔeGFR was significantly greater in the on-demand group compared to the daily group.  Multivariate analysis indicated that age > 40 years, baseline eGFR ≥ 90 mL/min/1.73m2, daily PrEP and switching were associated with a higher risk of negative eGFR variation.  Five participants (2 in the daily group, 2 in the on-demand group, and 1 in the switches group) experienced a > 25% reduction in eGFR on two consecutive measurements (incidence rate: 2.5 per 1000 person-years).  Fanconi syndrome was not reported.  Two participants stopped PrEP because of eGFR decreases but were subsequently re-challenged without incident.

Author’s Commentary:

Despite slight differences in eGFR variation over the initial 2 years of PrEP use (using tenofovir disoproxil fumarate), investigators concluded renal safety was favorable regardless of dosing strategy.  On-demand PrEP appears to have a smaller impact on eGFR change compared to daily use, but this difference does not appear to be clinically meaningful.  Further, the mean eGFR variation for the on-demand group was close to that previously described for DISCOVER trial participants taking daily PrEP using tenofovir alafenamide.  As other studies have suggested, older age is independently associated with increased risk of eGFR reduction – findings from this analysis would suggest that on-demand PrEP may be a reasonable option for older adults and others at risk of kidney dysfunction.

The author has no conflicts of interest to disclose.

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