Truvada PrEP Not Linked with Major, Lasting Kidney Problems
Although safe and well tolerated, Truvada (also referred to as FTC/TDF) has been linked with kidney dysfunction in people taking it to treat HIV disease. Would the same be true of HIV-negative people taking the pill daily? Most studies evaluating the kidney-health effects of Truvada, which combines the antiretroviral drugs tenofovir (Viread) and emtricitabine (Emtriva), have focused on people living with HIV, so researchers looked for answers in data from the large iPrEx study of Truvada PrEP.
The iPrEx trial enrolled 2,499 HIV-negative gay and bi men and transgender women who have sex with men. At screening and enrollment and at regular monitoring visits, participants in both the Truvada and placebo arms underwent tests to assess renal (kidney) function—that is, how well the kidneys are working to rid the body of waste products and reabsorb substances the body needs. A subset of study participants were also tested for proximal renal tubulopathy, a condition that has been tied to bone loss in people taking Truvada for HIV treatment.
Analysis revealed a small but statistically significant decrease in creatinine clearance in the Truvada group compared with those taking placebo pills, indicating a slight decline in the kidneys’ ability to remove the waste product creatinine from the body. This effect was first observed at week 4 of the study, with a mean (average) change of –2.4 mL/min in the Truvada arm vs. –1.1 mL/min in the placebo group.
This difference lasted through the final visit on treatment, with a mean between-group change ranging from –2.7 to 0.038 ml/min over the full 144 weeks of the study. Truvada’s effect on creatinine clearance did not differ by age, race, or history of high blood pressure—all known risk factors for renal dysfunction.
Importantly, the difference in creatinine clearance resolved when treatment was stopped. Although 62 creatinine elevations were recorded (37 in the Truvada group and 25 in the placebo arm), “[i]n none of the confirmed creatinine elevations…were there coincident elevations in blood-urea nitrogen (BUN) or decreases in serum bicarbonate,” changes that would have raised red flags for kidney dysfunction.
In addition, the research team detected no statistically significant effect of FTC/TDF on serum phosphorus levels or protein or glucose in the urine—signals of reduced kidney health. In the substudy assessing 1,137 participants for proximal renal tubulopathy, two cases were found in the placebo arm and none among those taking Truvada.
The authors call out an important limitation of this analysis: Participants in iPrEx (as in many other clinical trials) were required to have normal kidney function at study start. “Demonstration projects may also provide additional data on frequency of monitoring required or factors that will enable clinicians to identify those at greatest risk for renal effects of TDF,” the researchers observe. “The next step will be to monitor renal safety as PrEP is offered to broader populations with multiple comorbidities including pre-existing renal disease or predisposing risk factors for it (e.g. older age or diabetes) to determine whether FTC/TDF’s effects on renal function are similarly modest in these populations.”
Despite this limitation, the analysis supports the Centers for Disease Control and Prevention’s interim PrEP guidance around regular kidney function testing, and has implications for managing PrEP use in “real world” settings. The research team offers a suggestion to providers who detect creatinine elevation in their PrEP-using patients: Don’t rush to stop PrEP. “We advise repeating the abnormal serum creatinine measurements on a separate specimen before discontinuing FTC/TDF because the majority of elevations are self-limited,” the researchers write.
These findings underscore the importance of both regular kidney function monitoring for people on PrEP and the value of continued provider education, as demo projects and experience from clinical practice inform how to best use this relatively new HIV prevention tool.
Reilly O’Neal is a freelance writer and former editor of BETA.
Solomon, M. and others. Changes in renal function associated with oral emtricitabine/tenofovir disoproxil fumarate use for HIV pre-exposure prophylaxis. AIDS. February 4, 2014. (Epub ahead of print.)