IDSA 2011: Tenofovir Not Linked to Increased Kidney Risk in HIV+ Veterans Study

Use of tenofovir (Viread, also in the Truvada and Atripla coformulations) was not associated with a higher risk of kidney toxicity compared with other antiretroviral agents, according to a study presented at the 49th Annual Meeting of the Infectious Diseases Society of America (IDSA 2011) last month in Boston.

Tenofovir and related nucleotide reverse transcriptase inhibitors are cleared by glomerular filtration and active tubular secretion in the kidneys, and have the potential to cause renal toxicity. While tenofovir was not associated with significantly increased risk of kidney problems in pivotal clinical trials, observational and randomized studies since the drug's approval have produced conflicting data.

Overall, research suggests that tenofovir can contribute to impaired kidney function over time in a small proportion of susceptible patients. This may be more likely to occur when tenofovir is taken with a ritonavir-boosted HIV protease inhibitor (PI), which can raise tenofovir concentrations in the body.

To shed further light on this issue, Seema Nayak from the Veterans Affairs Medical Center in Washington, DC, and colleagues compared outcomes among patients at their facility who took tenofovir combined with either a boosted PI or a non-nucleoside reverse transcriptase inhibitor (NNRTI), those taking other HIV drugs, and people not yet receiving antiretroviral therapy (ART).

This retrospective analysis included 650 participants who met the inclusion criteria, out of a population of 1021. Almost all were men, about 85% were African-American (a group with a higher rate of kidney disease), and the average age was about 46 years.

Several factors associated with increased risk of kidney dysfunction -- including male sex, older age, black race/ethnicity, hypertension (about 35% overall), diabetes (about 12%), and history of kidney failure (about 4%) were similar across groups. However, other kidney risk factors including hepatitis C coinfection, renal insufficiency at baseline, and use of other (besides antiretroviral) drugs known to cause kidney toxicity varied significantly between groups.

At baseline and at 6 and 12 months the researchers measured creatinine levels and looked at 2 indicators of kidney function: creatinine clearance (Cockroft-Gault method); and glomerular filtration rate (GFR) using the Modification of Diet and Renal Disease (MDRD) equation, which takes into account patient sex, age, race, and serum creatinine.


Based on these findings, the researchers concluded that using tenofovir plus a boosted PI caused "no significant reduction in creatinine clearance or estimates of renal function" during a 12-month period, compared with tenofovir plus a NNRTI, other antiretrovirals, or no treatment

They added that these data "demonstrated the relative safety" of tenofovir plus a boosted PI, even in a patient population primarily made up of African-American men with high prevalence of hypertension and diabetes.

While these findings are reassuring, kidney problems related to tenofovir or other drugs may progress over time, so longer-term follow-up is needed.

Investigator affiliations: Medical Service, Infectious Diseases Section, Veterans Affairs Medical Center District of Columbia, Washington, DC; George Washington University, Washington, DC; Veterans Affairs Medical Center District of Columbia, Washington, DC.



SU Nayak, M Czarnogorski, R Amdur, and VL Kan. Renal Function in HIV-Infected Veterans on Tenofovir with and without Ritonavir Compared with Those on No Tenofovir and No Antiretroviral Therapy. 49th Annual Meeting of the Infectious Diseases Society of America (IDSA 2011). Boston, October 20-23, 2011. Abstract 402.