Truvada PrEP does not harm the kidneys, trial shows

HIV pre-exposure prophylaxis (PrEP) with FTC/tenofovir (Truvada) is associated with only mild disturbances in kidney function, investigators report in the online edition of AIDS. Creatinine clearance declined slightly but significantly four weeks after starting therapy with Truvada and this decline persisted for the duration of treatment. However, kidney function returned to normal after treatment was stopped.

The authors believe their findings support recommendations for the routine monitoring of creatinine clearance among people taking Truvada PrEP.

Results of the iPrEx study involving 2499 HIV-negative men who have sex with men and transgender women showed that daily Truvada PrEP reduced the risk of HIV infection by 44% compared to placebo. Truvada was approved for use as PrEP by the US Food and Drug Administration in July 2012 and interim guidance about its use has been issued by the Centers for Disease Control and Surveillance (CDC) and the World Health Organization (WHO).

Tenofovir is generally a safe and well-tolerated drug. However, when used by people living with HIV it has been associated with kidney dysfunction. In most cases, this is mild and resolves after treatment is stopped. But some more serious cases involving Fanconi syndrome have been observed.

Investigators from the iPrEx study wished to see if tenofovir-containing PrEP was also associated with a risk of kidney dysfunction in HIV-negative individuals.

Participants enrolled in the placebo-controlled study had a series of tests at regular intervals to monitor their renal function. These included creatinine clearance, serum phosphorus, and urine dipstick tests to detect protein (proteinuria) and glucose (glucosuria). A subset of participants was also assessed for proximal renal tubulopathy.

Approximately half the participants were aged between 18 and 24 years, 5% were black/African American, 5% had a body mass index (BMI) above 30 kg/m² and 5% had a history of hypertension (high blood pressure).

There was a small but significant decrease in creatinine clearance from baseline among people taking Truvada compared to the placebo arms (-2.4 vs -1.1 ml/min; p = 0.02). This difference emerged after four weeks of therapy and persisted until the end of treatment (p = 0.02). However, creatinine clearance normalised after the cessation of therapy (-0.0 vs 0.0 ml/min).

The effect of Truvada on creatinine clearance was unaffected by known risk factors for kidney dysfunction, including hypertension, race, age and higher body BMI.

There was a non-significant trend for a greater decrease in serum phosphorus levels among the participants taking Truvada compared to placebo (week 4 = -0.06 vs -0.01 mg/dl; p = 0.06).

The frequency of creatinine elevations did not differ between the treatment and placebo arms (n = 37 vs 25; p  = 0.28).

Analysis of urine dipstick results showed no difference in the proportion of people with proteinuria (Truvada = 21% vs placebo = 20%) or glucosuria (3% for both groups).

After the discontinuation of therapy, two participants – both in the placebo arm – had proximal tubulopathy.

The investigators acknowledge a number of limitations. The mean duration of therapy was 81 weeks, thus limiting their ability to determine the longer-term effects of Truvada PrEP. Low adherence to therapy was another limitation, and the authors note “stratifying the analysis according to FTC/TDF drug detection in the active arm indicated a dose response that was significant at some time points.”

They conclude their findings support CDC guidance that “oral FTC/TDF PrEP should include monitoring of serum creatinine…we advise repeating the abnormal serum creatinine measurements on a separate specimen before discontinuing FTC/TDF because the majority of elevations are self-limited.”