Truvada (tenofovir/emtricitabine) as pre-exposure prophylaxis (PrEP) against HIV leads to a small drop in kidney function after 12 weeks, a shift that remains stable thereafter. Such a shift is associated with high adherence to the daily regimen. Researchers charted changes in kidney function among 557 initially HIV-negative men who have sex with men (MSM) and transgender women in U.S. PrEP Demonstration Project, which was conducted at sexually transmitted infection clinics in Miami and San Francisco and a community health center in Washington, D.C., between September 2012 and January 2014.

Findings were presented at the 2016 Conference on Retroviruses and Opportunistic Infections (CROI) in Boston.

The participants were instructed to take Truvada daily for 48 weeks, and had their creatinine tested every 12 weeks. The researchers then calculated the participants’ eGFR levels based on the results of those tests.

At the outset of the study, the median eGFR among the participants was 97.1. The 25th percentile result was 85.7 and the 75th percentile result was 112. Six percent of the participants had an eGFR below 70 at this time.

An eGFR below 70 is an indicator of mildly reduced kidney function and a cause for more frequent testing, while a read greater than 90 is considered normal.

The researchers tested the tenofovir levels (tenofovir is one of the two drugs in Truvada) in a subset of 272 participants in order to estimate their adherence to the daily medication regimen.

On average, the eGFR level in the participants dropped 2.8 percent between the outset of the study and week 12, and then remained stable through week 48. Eleven participants (2.4 percent) had a decline of 10 percent or more in eGFR and a creatinine increase of at least 0.2 milligrams per deciliter at two or more consecutive study visits. Four participants (0.8 percent) had a greater than 25 percent loss in eGFR that was confirmed through repeat testing.

Previous research has shown that declines in eGFR among those taking Truvada as PrEP reverse after stopping the drug.

The researchers instructed three participants temporarily to stop taking Truvada because of elevated creatinine of greater than 1.5 times the baseline read. However, this shift in creatinine was not confirmed after repeat testing and the participants were then instructed to restart Truvada. After that point, the creatining elevations did not recurr.

Those who adhered better to the daily Truvada regimen were more likely to experience a drop in eGFR at week 12. Those who took less than two tablets per week experienced an average increase of about 5.5 percent, while those who took two to three tablets per week experienced a drop of 2 percent, and those who took at least four tablets per week experienced about a 4 percent drop. The difference in eGFR between those in these latter two adherence categories was statistically significant, meaning it is very unlikely the difference occurred by chance. However, the difference in eGFR between those taking two to three tablets a week was not statitsically significant compared with the eGFR change in those taking Truvada less frequently. The lack of statistical significance in this case may be a byproduct of the study’s small sample size of individuals who had their adherence levels tested.

Fifty-nine participants (12.6 percent) experienced a new eGFR result below 70 during the study follow-up period. Those who started the study with an eGFR below 90 were more likely to have their eGFR fall below 70, and this was particularly true for older individuals. The study authors indicate that these people may warrant additional monitoring.

Truvada adherence levels were not associated with newly developing an eGFR below 70.