Tenofovir linked with risk of kidney damage

via UCSF, by Steve Tokar

Tenofovir, one of the most effective and commonly prescribed antiretroviral medications for HIV/AIDS, is associated with a significant risk of kidney damage and chronic kidney disease that increases over time, according to a study of more than 10,000 patients led by researchers at the San Francisco VA Medical Center (SFVAMC) and the University of California, San Francisco (UCSF).

The researchers call for increased screening for kidney damage in patients taking the drug, especially those with other risk factors for kidney disease.

In their analysis of comprehensive VA electronic health records, the study authors found that for each year of exposure to tenofovir, risk of protein in urine – a marker of kidney damage – rose 34 percent, risk of rapid decline in kidney function rose 11 percent and risk of developing chronic kidney disease (CKD) rose 33 percent. The risks remained after the researchers controlled for other kidney disease risk factors such as age, race, diabetes, hypertension, smoking and HIV-related factors.

For individual patients, the differences in risk between users and non-users of tenofovir for each year of use were 13 percent vs. 8 percent for protein in urine, 9 percent vs. 5 percent for rapidly declining kidney function and 2 percent vs. 1 percent for CKD. “However, these numbers are based on the average risks in our study population, and patients with more risk factors for kidney disease would be put at proportionately higher risk,” said principal investigator Michael G. Shlipak, MD, MPH, chief of general internal medicine at SFVAMC and professor of medicine and epidemiology and biostatistics at UCSF.

Patients were tracked for an average of 1.2 years after they stopped taking tenofovir. They remained at elevated risk for at least six months to one year compared with those who never took the drug, suggesting that the damage is not quickly reversible, said Shlipak. “We do not know the long-term prognosis for these patients who stop tenofovir after developing kidney disease,” he cautioned.

The implications for patients already on or starting antiretroviral therapy are “mixed,” said Shlipak. “The best strategy right now is to work with your health care provider to continually monitor for kidney damage. Early detection is the best way to determine when the risks of tenofovir begin to outweigh the benefits.”

Shlipak noted that HIV, itself, increases the risk of kidney damage, while modern antiretroviral treatments clearly reduce that overall risk. “Patients need to be aware of their kidney disease risks before they start therapy, and this should influence the medications that they choose in consultation with their doctor,” he said. “For an otherwise healthy patient, the benefits of tenofovir are likely to exceed the risks, but for a patient with a combination of risk factors for kidney disease, tenofovir may not be the right medication.”

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[Content that is linked from other sources is for informational purposes and should not construe a Mapping Pathways position.]

MTN Statement on Decision to Discontinue Use of Oral Tenofovir Tablets in VOICE, a Major HIV Prevention Study in Women

via Microbicide Trials Network

VOICE, an HIV prevention trial evaluating two antiretroviral (ARV)-based approaches for preventing the sexual transmission of HIV in women – daily use of one of two different ARV tablets or of a vaginal gel – will be dropping one of the oral tablets from the study. The decision to discontinue use of tenofovir tablets in VOICE comes after a routine review of study data concluded that the trial will not be able to demonstrate that tenofovir tablets are effective in preventing HIV in the women enrolled in the trial. VOICE will continue to test the safety and effectiveness of the other oral tablet, Truvada®, a combination of tenofovir and emtricitabine, and of the vaginal gel formulation of tenofovir.

Importantly, the review, which was conducted by the National Institute of Allergy and Infectious Diseases (NIAID)’s independent Prevention Trials Data and Safety Monitoring Board (DSMB), identified no safety concerns with any of the products being studied in VOICE.

VOICE – Vaginal and Oral Interventions to Control the Epidemic – involves 5,029 women at 15 trial sites in Uganda, South Africa and Zimbabwe. The trial is being conducted by the Microbicide Trials Network (MTN), an HIV/AIDS clinical trials network funded by the National Institute for Allergy and Infectious Diseases with co-funding from the Eunice Kennedy Shriver Institute for Child Health and Human Development and the National Institute of Mental Health, all components of the U.S. National Institutes of Health.

The study was designed with five study groups: tenofovir gel, an inactive placebo gel, oral tenofovir, oral Truvada and an inactive placebo tablet. The women in each group (about 1,000) are asked to take their assigned study product daily. VOICE is the only trial evaluating the daily use of an ARV tablet – an approach called oral pre-exposure prophylaxis, or PrEP – and a vaginal gel in the same study. This design is important for determining how each product works compared to its control (placebo gel or placebo tablet) and which approach women prefer.

On September 16, 2011, the NIAID Prevention Trials DSMB reviewed VOICE study data for the period between Sept. 9, 2009, when the study began, and July 1, 2011. Based on this interim review, the DSMB determined that it was not possible to show whether oral tenofovir tablets were any better than a placebo for preventing HIV in the women assigned to that study group. The DSMB therefore recommended that the women randomized to the oral tenofovir tablet group discontinue their use of the study product. This recommendation does not apply to the women in the groups using either the tenofovir gel or oral Truvada tablets, or the corresponding placebos; the DSMB recommended that these four study groups continue in VOICE.

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[Content that is linked from other sources is for informational purposes and should not construe a Mapping Pathways position.]

Tricky Terminology in HIV Prevention – Part 2: “Microbicides” and “Oral PrEP”

“I think elegance must take second seat to being clear and helping people absorb vast amounts of new information.”

We recently blogged about the terms “abstinence” and “being faithful” – words that have caused a great deal of controversy in the HIV prevention arena. In this post, we discuss another instance of tricky terminology – the need to maintain the distinction between “oral PrEP” and “microbicides,” a difference that is extremely important in the context of the rapidly changing face of HIV prevention.

Lori Heise of the London School of Hygiene and Tropical Medicine has some thoughts on this matter. “In the next few years, as policymakers, providers, and potential users are trying to get their minds around all this new research and the expanding array of prevention options” she says, “it is absolutely essential that we stick to the language of ‘oral PrEP’ and ‘microbicides’ (for instance: ‘oral tenofovir’ or ‘tenofovir gel’).”

There has been a move within scientific circles to shift the language toward PrEP and ARVs, just making distinctions between mode of delivery (topical, oral, systemic), and there are supporters of this formulation. “However, as we shift from clinical trials into introduction and use,” she says, “we need every means at our disposal to help people make appropriate distinctions among methods.”(See this Mapping Pathways blog post for a snapshot of the various ways in which antiretrovirals can be used to prevent new HIV infections.)

Clear and accurate terminology help policymakers, advocates, and other stakeholders engage in rational discussions about which methods might best suit the needs of different individuals at different moments in time and with which types of partners or sexual settings. Substituting words or using umbrella terms tends to cloud clarity and cause confusion. “Over the last several months, I have sat through a number of presentations that combine information about oral PrEP and microbicides, but use the language of PrEP to describe both.” Lori recounts. “Even among groups of experts, I have noticed people getting confused – misapplying data, conclusions, or assumptions that mostly apply to microbicides or to oral PrEP, to both.There is a tendency to talk about PrEP and topical PrEP – but people don't register the ‘topical’ and so important nuances are lost.”

Indeed, these different products have critical distinctions to keep in mind. For instance, oral PrEP may potentially protect a wider range of users than microbicides, such as in the case of injection drug users (IDUs) whose primary risk of HIV infection is from tainted syringes, not unprotected sexual intercourse (though we are still waiting on data on the efficacy of PrEP among IDUs. Then, the license to develop tenofovir gel as a microbicide is held by the public sector, while the licenses for oral tenofovir and Truvada – both of which are already available for treatment – are controlled by Gilead. This dual-use issue where ARVs taken orally can be used for either treatment or prevention doesn't exist for any microbicide.

“These distinctions are important, and I think we need to use terminology that helps people keep them in the forefront of their minds – at least for the next few years, as we broaden the circle of discussion to add groups that as yet know very little about PrEP or microbicides....In this case,” says Lori, “I think elegance must take second seat to being clear and helping people absorb vast amounts of new information.”


[Content that is linked from other sources is for informational purposes and should not construe a Mapping Pathways position.]