On-Demand PrEP With TDF/FTC Not Associated With Clinically Relevant Decline in Kidney Function

On-demand pre-exposure prophylaxis (PrEP) with tenofovir disoproxil fumarate (TDF)/emtricitabine (FTC) is not associated with a significant relevant in kidney function, especially among young people with low pill use and high baseline estimated glomerular filtration rate, investigators in France found.

The research team set off to investigate whether on-demand PrEP— taken episodically before and after unprotected sex with an individual with HIV—resulted in the same small but statistically significant decrease in estimated glomerular filtration rate (eGFR) that is associated with daily PrEP use with TDF/FTC and with TDF use among patients with HIV.

In a study presented in an oral abstract session at the Annual Conference on Retroviruses and Opportunistic Infections (CROI 2019), investigators identified limited and nonclinically relevant eGFR decline among men who have sex with men (MSM) who take TDF/FTC for on-demand PrEP.

Investigators monitored eGFR in men who have sex with men (MSM) who did not have HIV with creatinine clearance >60mL/min at enrollment, months 1 and 2, and then every 2 months after as part of the randomized double-blind placebo-controlled ANRS-IPERGAY trial. In the blind phase, a total of 201 participants were randomized to receive placebo, while 199 participants received on-demand TDF/FTC, or a median number of 15 pills per month (interquartile range 11 to 21). The mean eGFR at baseline was 106mL/min/1.73m².

“During a median follow up of 9.3 months, the mean decline slope of eGFR was -0.13 and -0.07 mL/min/1.73m² per month in the TDF/FTC and placebo group, respectively (P = 0.27),” investigators reported in the abstract. “The cumulative proportion of patients with an eGFR <70mL/min/1.73m² at 12 months was higher on TDF-FTC: 8% [95%CI 4-13%] than placebo: 3% [CI 0-6%], P = 0.04. Compared to placebo, the risk of eGFR <70mL/min/1.73m² did not increase significantly in patients who took <15 pills/month: HR 1.75 [CI 0.65-4.7%] as compared [with] those using ≥15 pills/month: HR 2.54 [CI 1.07-6.04%].”

Overall, including both phases, small but significant eGFR decline occurred over time (mean slope: -0.09mL/min/1.73m² per month, P<0.01) among the 389 participants who initiated on-demand PrEP with a median follow up of 19.1 months. Two trial participants experienced persistent eGFR <60mL/min/1.73m², and 3 individuals discontinued TDF/FTC use because of a decline in kidney function.

But, investigators noted, “the cumulative proportion of eGFR <70mL/min/1.73m² from baseline was 14% [9-18%] at 24 months…Factors associated with eGFR <70mL/min/1.73m² were high pill use (HR 1.9 [CI 1.03-3.49%], P = 0.04), age > 40 years (P<0.01) and low eGFR at baseline (P<0.01).”

The study, “Changes in Kidney Function Among MSM Initiating On-Demand TDF/FTC for HIV PrEP,” was presented in an oral abstract session on Thursday, March 7, 2019, at CROI 2019 in Seattle, Washington.