Associations Between Tenofovir Use and Renal Complications in VA Cohort

May/June 2012

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This study was widely reported based on statistically significantly increases of 34% (proteinuria), 11% (rapid decline) and 33% (CKD) per year of exposure to tenofovir, after adjusting for traditional risks for renal complications, with increases from ever-use of 68%, 36% and 71% respectively.

As will all medical reports, relative rates (in this case, hazard ratios) have to also be interpreted together with data that supports the absolute risks associated with both tenofovir and non-tenofovir use.

Even given the generally low duration of use with tenofovir and limited follow-up after discontinuation, and that was a male study, these results are clearly important, especially when supported by other studies, such as the D:A:D analysis presented at CROI (see earlier in this issue of HTB).


Although the optimal way to define a rapid decline in kidney function is unclear, these seem like reasonable markers to have selected even though other groups (including D:A:D) use different criteria.

While it is unclear whether any minimum number of eGRF measures were needed when calculating the rate of decline within a year, as three or more would more accurately reflect a true decline rather than annual fluctuation but it is good that they excluded assessments of renal function during in-patient episodes as many other studies have not been able to do this.

With limited follow-up, it is difficult to separate the effect of "ever exposure" from "cumulative exposure" (and even with longer follow-up, this isn't always straightforward), but this will only become clear in future analyses.

As renal function was not always assessed during early the HAART period, patients with these early data may have had other renal complications requiring monitoring. However, the results did not change significantly when patients prior to 2001 were excluded.

Although the method of fitting the marginal structural models may be unclear, it is somewhat reassuring that similar results were found for all three models, suggesting that the results are robust to the choice of methodological approach.

The perceived risk of tenofovir and renal complications clearly affected the choice of early switching and explains the lack of associations with more advanced stages of CKD.


Scherzer R et al. Association of tenofovir exposure with kidney disease risk in HIV infection. AIDS. 26(7):867-875, April 24, 2012. doi: 10.1097/QAD.0b013e328351f68f.

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