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TDF-Based PrEP Associated With Increased Risk of Kidney Adverse Events, Review Finds


According to a review, few individuals initiating tenofovir disoproxil fumarate (TDF)–based HIV pre-exposure prophylaxis (PrEP) experienced clinically significant kidney impairment, although the risk was increased.

Among patients with HIV receiving tenofovir disoproxil fumarate (TDF)–based HIV pre-exposure prophylaxis (PrEP), risk of kidney-related adverse events (AEs) was increased but generally mild, according to a review published in Lancet HIV.

In 2015, World Health Organization (WHO) guidelines recommended offering once-daily TDF-based oral PrEP to individuals at substantial risk of contracting HIV, noting that the treatment was safe and well tolerated. Later in 2017, the WHO updated its guidelines, adding the recommendation for clinicians to measure creatinine clearance at PrEP initiation and at intervals during treatment.

However, past reviews found mixed results, with some studies demonstrating significantly increased kidney AE risk among individuals using TDF-based PrEP and others not.

To better understand the relationship between the treatment and kidney AE risk, the authors conducted a systematic review and meta-analysis, in addition to an individual participant data meta-analysis (IPDMA), both regarding kidney function among TDF-based PrEP users.

The meta-analysis included 11 randomized controlled trials (RCTs) containing data on AEs related to kidney function among 13,523 patients.

It found that use of TDF-based PrEP was associated with increased risk of grade 1 and higher kidney AEs (odds ratio [OR], 1.49; 95% CI, 1.22-1.81; I2 = 25%), which included an elevation of all serum creatinine levels by 1.1 to 1.3 times the upper limit of typical levels.

Risk of grade 2 and higher kidney AEs was also increased with TDF-based PrEP use (OR, 1.75; 95% CI, 0.68-4.49; I2 = 0%). However, the association was not statistically significant and events were rare, with 13 of 6764 in the intervention group and 6 of 6782 in the control group experiencing AEs.

In this category, serum creatinine levels increased by between 1.3 and 1.8 times the upper limit of typical levels, or between 1.3 and 1.5 times baseline value of the patient. Additionally, creatinine clearance dropped to less than 90 mL/min, or decreased by between 10% and 30% the patient’s baseline value.

The IPDMA included data on 18,676 individuals from 15 countries. The authors noted that a small amount (0.42%) had an estimated baseline creatinine clearance of less than 60 mL/min.

From this sample, data of 14,368 participants were included in a longitudinal analysis, which found that 349 (2.43%) participants experienced kidney function impairment following PrEP initiation.

Kidney AE risk was also found to increase proportionally with age. Creatinine clearance decline was associated with older age, baseline clearance between 60 and 89.99 mL/min (adjusted HR [aHR], 8.49; 95% CI, 6.44-11.20), and baseline clearance of less than 60 mL/min (aHR, 20.83; 95% CI, 12.83-33.82).

According to the authors, this indicates an increased frequency of creatinine clearance monitoring in older patients, and decreased frequency in younger patients.

Overall, few individuals initiating TDF-based PrEP experienced clinically significant kidney AEs.

The amount of patients lost to follow-up, lack of PrEP adherence data, potential survivor bias based on the higher proportion of men included in the research, and inability to determine a dose-response relationship between PrEP use and kidney function were listed as limitations.

“A more focused monitoring schedule has been suggested by WHO in the updated PrEP guidance, which might aid in reducing barriers to the implementation and scale-up of oral PrEP services,” the authors noted.


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

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