prophylaxis (PrEP) with tenofovir is associated with mild disturbances in
kidney function that resolve when treatment is stopped, investigators report in
the online edition of Clinical Infectious
Diseases. The study, in Thailand, involved people who inject drugs who took PrEP for up to
five years. Daily tenofovir therapy was associated with small decreases in key
measures of kidney function – creatinine
clearance and glomerular filtration rate (GFR) – but these reversed after stopping PrEP.
results…suggest that daily oral tenofovir can be used safely as a component of
HIV pre-exposure prophylaxis,” comment the authors. “It will be important to
include baseline assessments of renal function and routine monitoring of
creatinine clearance during follow-up.”
widely used in combination antiretroviral therapy. It has a potent anti-HIV
effect and a favourable safety profile. The drug is metabolised via the
kidneys and has been associated with renal dysfunction.
studies have shown that individuals taking tenofovir-containing PrEP have a
reduced risk of infection with HIV.
When used as PrEP,
tenofovir appears to be safe, but data from the iPrEx study (involving men who
have sex with men and transgender women) showed that PrEP with tenofovir/FTC
was associated with small but significant declines in creatinine function.
further assessed the renal safety of tenofovir PrEP using data collected during
the Bangkok Tenofovir Study.
This was a
randomised, double-blind, placebo-controlled trial involving HIV-negative people who inject drugs. Creatinine clearance and GFR were assessed using several
methods including the Cockcroft-Gault, Modification of Diet in Renal Disease
(MDRD) and Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI)
equations. Participants were monitored at twelve-month intervals for up to 60
months. Changes in kidney function were compared between the 1204 people taking tenofovir and the 1209 controls.
PrEP reduced the risk of infection with HIV by 49%. The frequency of deaths and
serious adverse events did not differ between the treatment and placebo arms of the study.
Cockcroft-Gault equation, 3% of participants had creatinine clearance below 50
ml/min. This outcome was significantly more common among people taking treatment compared to the controls (3.7% vs 2.2; p = 0.01).
formulas, at months 24, 36, 48 and 60, estimated creatinine clearance and GFR
results were lower in the tenofovir group compared to placebo.
At month 60,
estimated creatinine clearance was 5.2 ml/min lower among the tenofovir group than the controls (p = 0.03). Estimated GFR was 3.4 ml/min/1.73m2
lower using the MDRD formula (p = 0.0003) and 3.3 ml/min/1.73m2 when the CKD-EPI
formula was employed (p = 0.002). Modification to take into account the
characteristics of Thai patients did not alter these findings.
then looked at longitudinal changes in kidney function. A significant decline
in mean creatinine clearance was observed in the treatment arm (slope – 0.4, p
< 0.001), but not among people in the placebo arm. When the MDRD formula
was used, significant declines in GFR were observed in both the treatment and
placebo groups, with no difference in the slope between the groups. Declines in
GFR were also observed in both study arms when the CKD-EPI formula was used,
but this time the decline was significantly greater with tenofovir therapy (p =
analysis to people taking tenofovir showed that creatinine clearance was lower
in men than in women (p < 0.001) and also among people aged 30 and over compared
to those aged in their 20s (p = 0.002).
Follow-up of participants who discontinued therapy at the end of the study showed that
disturbances in kidney function associated with tenofovir were temporary and
had resolved a median of 20 months later.
suggest that with baseline assessments of renal function and routine monitoring
of creatinine clearance during follow-up, tenofovir can be safely used for
pre-exposure prophylaxis,” conclude the authors.