The potential for kidney toxicity associated with the popular HIV medication Viread ( tenofovir, also found in Truvada, Atripla, and Complera ) was once again confirmed in the largest study of the issue to date..
However, despite the new data from the Veterans' Administration ( VA ) , the tenofovir story remains the same: patients taking it should be monitored for kidney toxicity, especially if they have pre-existing risk factors such as hepatitis C, high blood pressure, or a family history of diabetes.
Positively Aware advisory board member Dr. Joel Gallant of Johns Hopkins University explains that, "While it's great to have new data from well designed studies, the VA study essentially confirms what we already know: that tenofovir can cause kidney damage in some people who take it. It shouldn't be surprising that the risk of kidney damage increases with longer time on the drug; that's true of most drug toxicities. The combination of tenofovir and emtricitabine [ Emtriva; combined to make up Truvada ] is still the preferred nucleoside backbone for most HIV-positive people in all current treatment guidelines, based on the wealth of clinical data demonstrating its effectiveness and safety. Tenofovir has been included in the vast majority of clinical trials involving initial antiretroviral regimens. These trials have universally shown excellent long-term safety, including minimal development of kidney toxicity. The risk of nephrotoxicity may be higher when it's combined with protease inhibitors, when it's used by older people or those with pre-existing kidney disease, or in people who are taking other drugs that can damage kidneys, such as the non-steroidal anti-inflammatory drugs ( e.g. ibuprofen ) ."
He added, "We know how to monitor for kidney toxicity, which generally happens gradually. We can always change drugs if it occurs."
Dr. Daniel S. Berger of Northstar Medical Center in Chicago, also a member of the PA advisory board, wrote, "Tenofovir was long known to be associated with kidney function risks, as is having HIV infection itself, but it more commonly occurs with other predisposing illnesses such as diabetes and hypertension. We monitor renal function routinely in our daily practice, as we do for other side effects."
The observational study conducted by the San Francisco VA Medical Center and the University of California, San Francisco looked at the electronic health records of nearly 11,000 VA patients with HIV ( the majority of them male ) . The study looked at three types of renal problemsproteinuria ( protein in the urine ) , rapid decline in kidney function, and the development of chronic kidney disease ( CKD ) , and found that the risk increased for people who had taken tenofovir versus those who hadn't.
Moreover, kidney toxicity remained after people stopped taking tenofovir, from out to six months to one year in this data, which showed that toxicity was not reversible, at least in the short term ( however, the follow-up was 1.2 years after tenofovir discontinuation, indicating that the risk did go away ) . These risks were found after weighing other risk factors such as older age, non-white race, and smoking.
The researchers wrote that, based on this data, "If you were to follow 1,000 HIV-infected patients for a year, you would expect to see 50 extra cases of significant protein in urine ( 132 events vs. 82 events ) , 38 extra cases of rapid decline ( 92 vs. 54 events ) , and 11 extra cases of chronic kidney disease ( 19 vs. 8 events ) in users of tenofovir versus non-users."
After controlling for other risk factors, they found that each year of tenofovir use was associated with a 34% increased risk of proteinuria, 11% increased risk of rapid decline in kidney function, and 11% increased risk of CKD.
Said Dr. Gallant in his e-mail message, "Remember that while an increased risk of 'up to 34%' sounds scary, this is not the same thing as a 34% risk. A 34% increase in a very low risk is still a very low risk. As an example, if your risk of developing kidney disease without tenofovir were 1% per year, and tenofovir increased your risk by 34% per year, then your risk of kidney disease on tenofovir in the first year would be 1.34%."
Added Dr. Berger, "What makes Viread and Truvada the most popular HIV treatment today, is its excellent safety profile, tolerability and the forgiveness provided by its long intracellular half-life ( longevity in the blood and cells ) . These characteristics are responsible for many important strides in HIV therapy and for many reasons that we currently observe much less nucleoside resistance with higher durability and lasting success of many HIV regimens overall."
The study was published in February in AIDS; see the entire report at www.natap.org .
Enid Vázquez is associate editor of Positively Aware magazine.