Three presentations at the 2016 Conference on Retroviruses and Opportunistic Infections (CROI) in Boston offered reassuring news that adverse kidney changes that accompany Truvada use for PrEP are rarely serious and universally reverse after stopping the medication, but also suggested that older people and those with the best adherence might need to be watched more closely.
Tenofovir disoproxil fumarate, one of the key ingredients in the combination pill Truvada, is known to affect kidney health in people living with HIV, but so is HIV itself. Thus, one of the big questions with the use of Truvada in HIV-negative people is whether kidney problems in PrEP users will be similar, or less frequent and severe, than in people using Truvada for treatment. In randomized controlled studies of PrEP, moderate to severe kidney troubles have been rare and completely reversible, but real world experience and more detailed analyses have been needed. The three presentations at CROI offered deeper insight into kidney health of people on PrEP.
The first presentation, from Monica Ghandi, M.D., M.P.H., analyzed the association of PrEP adherence with the occurrence and severity of reduced kidney function in participants from the iPrEx OLE demonstration project. She reported that when hair samples indicated high adherence, kidney problems -- though very rare -- were both more likely overall and more likely to be moderate to severe, compared with hair samples indicating poor adherence. In terms of clinically significant kidney function declines, however, age played a huge part. About a quarter of those over 50 had a clinically significant decline, compared with 5% in those under 40, even when the younger cohort had very high adherence.
A similar presentation from Albert Liu, M.D., M.P.H., looked at tenofovir levels in dried blood spots from men who have sex with men and transgender women enrolled in The Demo Project. Once again, higher tenofovir levels and older age were associated with greater reductions in kidney function, but this was also modified by pre-existing kidney health. Less than 2.4% had a decline in a test of kidney function (eGFR) of 10% or more, and drops reversed on cessation of PrEP, but the chance of kidney health declined was much lower in those with good kidney health at the start of the study.
A final presentation, from Kenneth Mygwanya, M.B.Ch.B., M.S., looked at the clinical significance of blood and urine measures of kidney function in those taking PrEP in the Partners PrEP study in heterosexual couples in Uganda and Kenya. While reductions in these measures of kidney function are meaningful and sizable reductions are a serious cause of concern, it is not clear how much tests of kidney function are associated with the actual clinical manifestation of the specific type of kidney damage caused by tenofovir, called proximal tubulopathy. What Mygwanya and his colleagues found was that this condition was rarely seen and not meaningfully different between those assigned to the Truvada arm of the study (1.7%) and those assigned to take a placebo (1.3%).
Taken together there are several conclusions and a big question. The first conclusion is that kidney problems are rare and reversible on PrEP. The second is that older people, those with higher adherence and those with poorer kidney function before starting PrEP could be at increased risk of developing clinically meaningful reductions in tests of kidney function. The third is that even when tests indicate a problem, the actual harms might be less than suggested by the tests.
A big remaining question is whether older people and those with moderately reduced kidney function (but not low enough to rule out PrEP) should be monitored more frequently and closely while on PrEP.
Monica Gandhi, et al. "Higher Cumulative TFV/FTC Levels in PrEP Associated With Decline in Renal Function". CROI 2016, Boston, MA. Abstract 866.
Albert Y. Liu, et al. "Changes in Renal Function Associated With TDF/FTC PrEP Use in the US Demo Project". CROI 2016, Boston, MA. Abstract 867.
Kenneth K. Mygwanya, et al. "Rare Incidence of Proximal Tubular Dysfunction With Tenofovir-Based Chemoprophylaxis". CROI 2016, Boston, MA. Abstract 868.