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.
believe their findings support recommendations for the routine monitoring of
creatinine clearance among people taking Truvada
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).
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.
the iPrEx study wished to see if tenofovir-containing PrEP was also associated
with a risk of kidney dysfunction in HIV-negative individuals.
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
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).
discontinuation of therapy, two participants – both in the placebo arm – had
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.”
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.”