Treatment with tenofovir causes long-term declines in kidney function, US investigators report in the January 1st edition of the Journal of Acquired Immune Deficiency Syndromes.
Their retrospective cohort study, which monitored patients for over two years, found that those taking tenofovir had more evidence of kidney dysfunction than individuals taking other antiretroviral drugs.
“Our study indicates a statistically significant effect of tenofovir on renal function in antiretroviral naïve patients initiating combination antiretroviral therapy”, comment the investigators.
Tenofovir (Viread, also in the combination pills Truvada and Atripla) is a nucleotide reverse transcriptase inhibitor that is recommended for first-line antiretroviral therapy.
It is generally a very safe and well-tolerated drug. However, soon after the drug was licensed there were case reports that suggested an association with kidney dysfunction.
Studies exploring the relation between treatment with the drug and kidney problems have produced contradictory results, and one recent study found that the risk of kidney dysfunction was the same for tenofovir as other antiretroviral drugs.
To better understand this issue, researchers retrospectively analysed the medical records of 1647 patients who were registered in the Kaiser Permanente cohort and started HIV treatment for the first time between 2002 and 2005.
Changes in three key markers of kidney function were analysed: glomerular filtration rate (GFR); serum creatinine; and the development of renal proximal tubular dysfunction.
A total of 964 patients were treated with tenofovir, the other 683 individuals taking other antiretroviral drugs. The two groups of patients had broadly similar baseline characteristics. However, the tenofovir-treated patients were more likely to be co-infected with hepatitis B virus (4% vs 2%, p = 0.004). Furthermore, patients taking tenofovir were significantly more likely to have also received therapy with a protease inhibitor (41% vs 36%, p = 0.03). Use of indinavir (Crixivan), a protease inhibitor associated with kidney dysfunction, was very low, being taken by only five of the tenofovir-treated patients and ten individuals taking other drugs.
Results showed that a significantly higher proportion of patients taking tenofovir had at least a 50% decline in GFR from baseline compared to those taking other drugs (5% vs 3%, p = 0.03).
The effect of tenofovir on GFR was confirmed in further analysis. This showed that after controlling for potentially confounding factors, treatment with tenofovir was associated with significant declines in GFR after 52 (p
In addition, levels of serum creatinine were higher amongst the tenofovir-treated patients at both week 52 (p
After 44 weeks of treatment, those taking tenofovir had a significantly greater risk of developing proximal tubular dysfunction (OR, 1.61, 95% CI: 1.00-2.60, p = 0.04). This risk increased with longer duration of treatment and was especially high at week 104 (OR, 5.23, 95% CI: 2.08-13.1, p = 0.004).
“We found statistically significant decreases in GFR and increases in serum creatinine, which appears progressive with time…we also found that tenofovir exposure is associated with a significantly greater risk of developing proximal tubular dysfunction, the risk of which increased over the time span of our study”, comment the investigators.
The investigators believe that their findings have clinical significance, and write: “We found the adverse renal effects of tenofovir persisted, even after controlling for a variety of potential other causes. Given the current commitment to long-term, even life-long antiretroviral therapy, incremental small annual declines in kidney function could eventually lead to kidney failure and increased mortality.”
They therefore recommend changes to tenofovir prescribing practices, including the “strategic use” of tenofovir in patients with a high risk of developing kidney problems.
“We conclude that although efficacious, the potential long-term adverse effects on kidney function may limit the use of tenofovir for patients at high risk of renal complications. Long-term monitoring of renal function and the components of proximal tubular dysfunction in patients taking tenofovir should be considered.”
Horbery M et al. Impact of tenofovir on renal function in HIV-infected, antiretroviral-naïve patients. J Acquie Immune Defic Syndr 53: 62-69, 2010.