On-demand versus daily PrEP may mitigate TDF’s effect on kidneys, reports French study

On-demand tenofovir disoproxil fumarate (TDF) may limit potential kidney issues relative to daily oral pre-exposure prophylaxis (PrEP), especially in older men and those with baseline estimated glomerular filtration rates (eGFR) ≤ 90 mL/min/1.73m², according to a recently published study conducted in Paris, France. The study also found that patients who developed complex kidney situations while on PrEP often were taking a protein supplement.

About This Study

“Incidence and Management of Complex Kidney Situations Among On-demand and Daily HIV Pre-exposure Prophylaxis Users” was published online on Nov. 16, 2023, in Journal of Acquired Immune Deficiency Syndromes. The lead author is Geoffroy Liegeon, M.D., Ph.D., of the Department of Infectious Diseases and Global Health at the University of Chicago, Illinois, and of the Department of Infectious Diseases at Assistance publique-Hôpitaux de Paris (AP-HP), Hôpital Saint Louis et Lariboisière, in Paris, France.

Key Research Findings

Current guidelines recommend against using TDF-based PrEP for people with an eGFR < 60mL/min/1.73m². However, previous studies have suggested that on-demand PrEP may have a better renal safety profile than daily PrEP.

This retrospective study assessed kidney issues in 3,114 people on TDF PrEP at a single Parisian clinic from 2012-2019. Almost all participants were men who have sex with men. Median age was 35 years, with 11% of participants ≥ 50 years old. At baseline, 65% of participants used on-demand PrEP—which remained similar at the study’s one-year mark (64%) even though participants were not required to remain on only one method.

Nine participants had a “complex kidney situation” (the occurrence of two consecutive measurements of eGFR< 60mL/min/1.73m²) at baseline, with five of them reporting protein supplement use for weight training. In seven of the nine participants, renal function returned to normal within a median 9.6 months while taking on-demand PrEP and one participant continued on-demand PrEP at an eGFR < 60 mL/min/1.73m².

During the study, eGFR dropped < 60 mL/min/1.73m² in 19 participants, with a complex kidney situation confirmed in 13 of them. Among these 13 participants, notable characteristics included four who reported protein supplement use and seven who were on daily PrEP. Three participants were lost to follow-up, and seven of the remaining 10 participants took on-demand PrEP (including two participants switched from daily PrEP).

After a median of 16.6 months of follow-up, none of the participants taking on-demand PrEP relapsed to eGFR < 60 mL/min/1.73m², while one participant experienced a relapse at five months but did not discontinue daily PrEP. Overall, predictors of complex kidney situations were age > 50 years and baseline eGFR < 90 mL/min/1.73m².

Discussion Highlights and Implications for Practice

Study limitations included a short follow-up time (median of 1.4 years). In addition, findings cannot be extrapolated to cis- or transgender women as on-demand PrEP is not currently recommended for them.

Results suggest that renal impairment may be less of an issue over time with on-demand compared to daily TDF PrEP. Further research is warranted, especially given that alternatives, such as tenofovir alafenamide or long-acting cabotegravir, are not available everywhere. Kidney function assessments should also consider the impact of protein supplements on eGFR measurements.

By Barbara Jungwirth