HIV pre-exposure 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.
“These 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.”
Tenofovir is 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.
Several clinical 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.
Now investigators 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.
Overall, tenofovir 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.
Using the 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).
Using all 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.
The investigators 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 = 0.007).
Restricting 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.
“These results 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.
Martin M et al. Renal function of participants in the Bangkok tenofovir study. Clin Infect Dis, online edition, 2014.