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Renal function declines associated with HIV preexposure prophylaxis (PrEP) are more likely with increasing age and decreasing baseline creatinine clearance, according to a new study.

“This is one of the first studies to systematically study predictors of renal decline on tenofovir disoproxil fumarate/emtricitabine (TDF/FTC)-based PrEP in a large cohort of men or transgender women,” Dr. Monica Gandhi from the University of California, San Francisco, told Reuters Health by email.

Several PrEP trials have shown small but significant reductions in renal function with the use of tenofovir fumarate and emtricitabine every day, Dr. Gandhi and colleagues note in The Lancet HIV, online August 31.

They used data from the global iPrEx trial’s open-label extension study of 1,224 men who have sex with men and transgender women on PrEP to identify predictors of declines in renal function with long-term exposure to tenofovir and emtricitabine.

During a median follow-up of 72 weeks, the average drop in creatinine clearance was 4.2 mL/min or 2.9%, the team found.

Declines in creatinine clearance increased with age, from 2.4% in those younger than 40 years to 4.2% in those aged 40-50 years and 4.9% in those aged 50 years or older.

Participants who started with higher creatinine clearance at baseline experienced significantly larger reductions in creatinine clearance over time.

The risk of creatinine clearance falling below 70 mL/min was significantly higher in participants who started PrEP at ages older than 40 years and in those who started PrEP with lower renal function at baseline.

Creatinine clearance fell to 60 mL/min in nine of more than 7,000 visits, but all nine of these falls occurred in participants who started with a creatinine clearance below 90 mL/min, and eight of nine events occurred in individuals aged 50 years or older when they started PrEP.

There was a monotonic association between percentage decrease in creatinine clearance and increasing quartile of tenofovir or emtricitabine concentrations in hair.

“Our analysis suggests that patients who are older, start out with compromised renal function, and are highly adherent to medications (as we hope to encourage) should be monitored more closely for safety, with creatinine checked at least every 6 months and perhaps quarterly if the creatinine clearance starts to show a downwards trend,” Dr. Gandhi said.

“However, we would also like to stress that our analysis of a large group of patients on PrEP suggests that renal monitoring for those who are young (<40 years) and have perfectly normal renal function at PrEP initiation may not need biannual monitoring,” she added.

“We believe strongly that PrEP should be brought into the mainstream for primary care providers to consider as a prophylactic strategy for their at-risk patients,” Dr. Gandhi said.

“We also want to stress that PrEP is safe and its known toxicities (mainly renal toxicity) easily discerned by routine laboratory monitoring,” she said. “Renal decline is usually reversible with cessation of PrEP if your patient shows signs of toxicity.”

Dr. Lene Ryom from the University of Copenhagen, Denmark, who coauthored a related editorial, told Reuters Health by email, “Whilst the nephrotoxic properties related to cumulative use of tenofovir in HIV-positive individuals are well-known by now, limited data has to date been available in healthy HIV-negative individuals. The results flag the need for any PrEP prescription to be followed by regular clinical follow-up visits including a renal risk assessment and estimation of renal function.”

“Recommendations for the type and frequency of monitoring of renal function in HIV-positive individuals are outlined in the European AIDS Clinical Society (EACS) guidelines that are updated annually,” she said. “Generally it is recommended to assess the overall renal risk profile annually, and screen for renal impairment using eGFR every 3-12 months depending on the renal risk profile (including use of potential nephrotoxic agents) and current level of renal function. In addition, assessment of proteinuria is recommended annually if renal function is normal or semi-annually if eGFR<60 mL/min.”

Dr. Dawn Smith from the U.S. Center for Disease Control and Prevention’s Division of HIV/AIDS Prevention in Atlanta, Georgia, told Reuters Health by email, “We estimate that approximately 1.2 million adults have indications for PrEP use in the U.S. but <5% of them have been prescribed PrEP as of December 2015. Health care providers need to educate patients about this new prevention method and screen their patients to identify those who would benefit from its use including routine HIV testing of sexually active adults in their practices.”

“Clinicians wanting clinical advice about how to screen patients, prescribe PrEP, or monitor patients on PrEP can call the toll-free PrEPline at 855-448-7737 to speak with the Clinician Consultation Center,” she said.

Gilead Sciences donated study drug, but otherwise had no input into the study.

SOURCE: http://bit.ly/2cPXGXR and http://bit.ly/2caeBmz

Lancet HIV 2016.

Original Article

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