Kidney Impairment in Older vs Younger Patients on HIV Pre-Exposure Prophylaxis

In patients receiving tenofovir disoproxil fumarate (TDF)-based HIV pre-exposure prophylaxis (PrEP), the risk for kidney impairment was found to increase proportionally with age, indicating that the frequency of creatinine clearance monitoring should be increased in patients older than 50 years and decreased in younger patients. These findings were published in Lancet HIV.

Previously, guidelines from the World Health Organization (WHO) recommended measuring creatinine clearance at PrEP initiation and then at regular intervals thereafter. In this review and meta-analysis, researchers reviewed results of studies published through June 2021 that assessed kidney-related adverse events among patients receiving either TDF-based PrEP alone or in combination with either emtricitabine or lamivudine. Researchers also performed an individual participant data meta-analysis (IPDMA) on kidney function among PrEP users in a global implementation project dataset.

A total of 11 randomized controlled trials comprising 13,523 patients were included in this meta-analysis. Summary data were extracted, and a random-effects model was used to estimate the relative risk for kidney-related adverse events of grade 1 and higher and grade 2 and higher. Estimated creatinine clearance was calculated at baseline and after PrEP initiation, with adjustments made for patients’ age, sex, and comorbid conditions. Random-effects regression was used to estimate the risk for kidney function impairment (creatinine clearance, <60 mL/min).

The researchers found that PrEP use was associated an increased risk for kidney-related adverse events of grade 1 or higher (pooled odds ratio [OR], 1.49; 95% CI, 1.22-1.81; I²=25%). An increased risk for grade 2 and higher events was also associated with PrEP use, but the association was not statistically significant (OR, 1.75; 95% CI, 0.68-4.49; I²=0%).

In the (IPDMA) that included 18,676 individuals from 15 countries, 79 (0.42%) had an estimated creatinine clearance of less than 60 mL/min at baseline. Results of a longitudinal analysis comprising 14,368 found that 349 (2.43%) experienced kidney function impairment following PrEP initiation. A decline in creatinine clearance was also found to be associated with older age, as well as a baseline clearance between 60 and 89.99 mL/min (adjusted hazard ratio [aHR], 8.49; 95% CI, 6.44-11.20) and a baseline clearance of less than 60 mL/min (aHR, 20.83; 95% CI, 12.83-33.82).

Study limitations included the number of patients lost to follow-up, the lack of data on PrEP adherence, and the inability to evaluate a dose-response relationship between PrEP use and its effect on kidney function. In addition, there was potential survivor bias and women were underrepresented in the dataset. 

According to the researchers, “logistical challenges and costs associated with creatinine screening at and regularly after PrEP initiation might be barriers to PrEP service implementation and uptake.” They concluded that “less frequent or optional screening among younger individuals without kidney-related comorbidities might be appropriate.”

Disclosure: Some authors declared affiliations with biotech, pharmaceutical, and/or device companies, and this research was supported by Unitaid, Bill & Melinda Gates Foundation, and WHO. Please see the original reference for a full list of disclosures. 

Reference

Schaefer R, da Costa Leite PHA, Silva R, et al. Kidney function in tenofovir disoproxil fumarate-based oral pre-exposure prophylaxis users: a systematic review and meta-analysis of published literature and a multi-country meta-analysis of individual participant data. Lancet HIV. Published online March 7, 2022. doi:10.1016/S2352-3018(22)00004-2