Tenofovir-associated kidney problems not always reversible

Michael Carter
Published: 01 March 2010

Kidney function does not always return to normal after treatment with tenofovir is discontinued because of renal toxicities, Australian investigators report in an advance online publication in the Journal of Acquired Immune Deficiency Syndromes.

An average of 13 months after therapy with tenofovir was stopped, over 40% of patients still had evidence of impaired kidney function.

A gradual decline in kidney function during therapy with tenofovir was identified as a risk factor for the persistence of renal problems.

Tenofovir (Viread, also in the combination pills Truvada and Atripla) is recommended for use as part of first-line HIV therapy. The drug is generally considered safe, but between 1-2% of patients develop serious kidney impairment whilst taking it. Risk factors for this side-effect include the use of other drugs that cause renal toxicities, co-infections, a low CD4 cell count, and injecting drug use.

Reports suggest that kidney function, as monitored by creatinine clearance, returns to normal soon after therapy with tenofovir is stopped.

But Australian investigators were concerned that creatinine clearance is not a sensitive measure of kidney function.

They therefore monitored estimated glomerular filtration rate, a more accurate measure of kidney function, in 24 HIV-positive men who discontinued tenofovir therapy because of kidney dysfunction.

The investigators defined renal impairment as an estimated glomerular filtration rate below 90 ml/m-1/1.73-2.

All the men in the study were white, 79% received therapy with a protease inhibitor, and 81% had a viral load below 50 copies/ml.

The median duration of tenofovir therapy at the time of cessation was 30 months.

Most of the patients had evidence of kidney dysfunction before treatment with tenofovir was initiated.

However, during therapy with the drug, median estimated glomerular filtration rate declined from 74 ml/m-1/1.73-2 to 51 ml/m-1/1.73-2.

The patients were followed for a median of 13 months after treatment with tenofovir was withdrawn and changes in kidney function were monitored.

During this time, median estimated glomerular filtration rate increased to 70 ml/m-1/1.73-2. The greatest improvement occurred in the first month after stopping treatment with tenofovir.

At the end of follow-up, both the most improved estimated glomerular filtration rate and the latest estimated glomerular filtration rate were both significantly below the levels recorded before therapy with tenofovir as started (p = 0.028 and p = 0.0008).

Investigators then compared the characteristics of patients with improvements in estimated glomerular filtration rate above 20 ml/m-1/1.73-2 and those with improvements below this level.

Their analysis showed that a more rapid decline in kidney function (p = 0.009), treatment with a protease inhibitor (p = 0.02) and shorter duration of therapy with tenofovir (p = 0.08) were all associated with greater gains in estimated glomerular filtration rate once tenofovir was stopped.

They suggest that acute changes in kidney function were less likely to lead to long-term problems than slow, gradual declines in renal function.

“Improvement in renal function after tenofovir cessation is variable and incomplete, particularly in patients with more gradual decline in estimated glomerular filtration rate who are not receiving a protease inhibitor”, comment the investigators.

They therefore conclude, “a decline in estimated glomerular filtration rate, even if gradual and to a level above 60 ml/m-1/1.73-2, may merit discontinuation of tenofovir to avoid permanent renal dysfunction.”

Reference

Wever K et al. Incomplete reversibility of tenofovir-related renal toxicity in HIV-infected men. J Acquir Immune Defic Syndr (online edition), 2010.

Community Consensus Statement on Access to HIV Treatment and its Use for Prevention

Together, we can make it happen

We can end HIV soon if people have equal access to HIV drugs as treatment and as PrEP, and have free choice over whether to take them.

Launched today, the Community Consensus Statement is a basic set of principles aimed at making sure that happens.

The Community Consensus Statement is a joint initiative of AVAC, EATG, MSMGF, GNP+, HIV i-Base, the International HIV/AIDS Alliance, ITPC and NAM/aidsmap
close

This content was checked for accuracy at the time it was written. It may have been superseded by more recent developments. NAM recommends checking whether this is the most current information when making decisions that may affect your health.

NAM’s information is intended to support, rather than replace, consultation with a healthcare professional. Talk to your doctor or another member of your healthcare team for advice tailored to your situation.