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  18th European AIDS Conference
October 27th-30th, 2021
Online & United Kingdom
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Kidney Toxicity Rare With Daily or On-Demand (As-Needed) PrEP
  18th European AIDS Conference, EACS 2021, October 27-30, 2021, London
Mark Mascolini
Kidney toxicity proved rare with either daily tenofovir/emtricitabine (TDF/FTC) preexposure prophylaxis (PrEP) or on-demand (as-needed) TDF/FTC PrEP in a 1253-person analysis from May 2017 to October 2020 [1]. Kidney adverse events did not lead anyone to stop PrEP in this French ANRS-Prevenir study group. Changes in estimated glomerular filtration rate (eGFR), a measure of kidney function, favored on-demand PrEP, but the difference from the daily PrEP group was not clinically meaningful.
Plentiful research establishes kidney toxicity as a major adverse effect of tenofovir disoproxil fumarate (TDF), whether taken to treat or prevent HIV infection. Because on-demand TDF/FTC PrEP proved as effective as daily PrEP in preventing HIV infection in the prospective Prevenir cohort study [2], many hoped that taking TDF less often in the on-demand format would lower side effect rates.
In this analysis Prevenir researchers aimed mainly to compare changes in kidney function with the two PrEP strategies as determined by eGFR. From the initial Prevenir population of 3067 people, mainly men who have sex with men (MSM), the investigators eliminated participants already taking PrEP at enrollment and those who did not have a baseline creatinine measure.
From May 2017 to October 2020, 499 Prevenir participants took TDF/FTC PrEP daily, 494 took TDF/FTC on demand, and 260 switched from one strategy to the other. Everyone had eGFR determined every 3 months.
About 85% of participants were white and 98% MSM. Median age varied slightly but significantly between the on-demand group (35 years), the daily group (34 years), and switchers (32 years) (P = 0.01). The daily group averaged more pills weekly than switchers or on-demand participants (6.0 vs 4.0 vs 1.7, P < 0.01). Baseline eGFR did not differ significantly between those 3 groups (105, 103, and 103 mL/min, P = 0.12). The proportion who used other kidney-toxic drugs was higher in daily PrEP users (7%) than in on-demand users (4%) or switchers (3%) (P = 0.03). Median follow-up was longer in switchers than in daily users or on-demand users (24.5 vs 22.6 vs 21.1 months, P < 0.01).
Through 24 months of follow-up, eGFR improved modestly (by about 3 mL/min) in the on-demand group while staying essentially flat in the daily group and switchers. Average area under the curve (AUC) for change in eGFR through 24 months differed significantly between the on-demand group (+0.18 mL/min, 95% confidence interval [CI] -0.57 to 0.93) versus the switch group (-0.69 mL/min, 95% CI -1.72 to 0.34) and the daily group (-1.09 mL/min, 95% CI -1.83 to -0.34) (P = 0.02).
Multivariable analysis linked three factors to a greater AUC for change in eGFR: on-demand PrEP (odds ratio [OR] 1.47, 95% CI 0.70 to 2.25), age 40 or younger (OR 1.63, 95% CI 0.94 to 2.32), and baseline eGFR below 90 mL/min (OR 3.68, 95% CI 2.72 to 4.64).
The Prevenir investigators summarized the eGFR findings by stating that "on-demand PrEP dosing had a smaller impact on eGFR evolution than daily PrEP, but the difference was not clinically relevant."
Serious kidney adverse events proved rare with all 3 PrEP methods-daily, on-demand, and switching. Among the 1253 people in this analysis, the researchers counted 5 cases of two consecutive eGFR drops of at least 25% (1 with daily PrEP, 3 with on-demand PrEP, and 1 with switching; overall incidence 0.25 per 100 person-years); 5 cases of two consecutive eGFRs below 60 mL/min (2 with daily PrEP, 2 with on-demand PrEP, and 1 with switching; overall incidence 0.25 per 100 person-years); 2 cases of kidney-related temporary PrEP discontinuation (1 with daily PrEP, 1 with on-demand PrEP; overall incidence 0.10 per 100 person-years); and no cases of kidney-related permanent PrEP discontinuation.
The Prevenir team concluded that "the renal safety profile of daily and on-demand [TDF/FTC] PrEP was very good." They argued that concerns about kidney safety should not be a barrier to TDF/FTC PrEP.
1. Liegeon G, Assoumou L, Ghosn J, et al. Renal safety of on-demand and daily TDF-FTC for HIV pre-exposure prophylaxis in the ANRS-PREVENIR study. 18th European AIDS Conference, EACS 2021, October 27-30, 2021, London. Abstract BPD2/8.
2. Molina JM, Ghosn J, Delaugerre C, et al. Incidence of HIV infection with daily or on-demand oral PrEP with TDF/FTC in France. Conference on Retroviruses and Opportunistic Infections (CROI). 2021. Abstract 148.