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Hi, this is Paul Sax from Brigham and Women's Hospital and Harvard Medical School. Today I would like to review another study that was recently presented at the International AIDS Society (IAS) meeting in Rome, Italy. As you may know, in 2010, the World Health Organization (WHO) issued guidelines about initial antiretroviral therapy options, suggesting that d4T (stavudine) be phased out in favor of tenofovir-based regimens. This was recommended for obvious reasons, the toxicity being so much lower. The 4 recommended regimens were tenofovir with either lamivudine (3TC) or emtricitabine (FTC). The third drug is efavirenz/nevirapine therapy, so that's 4 different regimens.

The abstract presented at IAS[1] was a systematic review of studies of these 4 regimens. They found that first, the tenofovir 3TC/nevirapine regimen was the least well studied of the group. Only 3 studies were identified. Second, when they looked at the virologic efficacy of this regimen, they found a fairly high rate of virologic failure (20%-30%). Furthermore, this was accompanied by a very high rate of K65R, which is a mutation that is seen fairly uncommonly in the United States, and seems to be more common with the subtype C virus.

Their conclusion was that the tenofovir 3TC/nevirapine regimen really needs to be studied more before it is broadly implemented. The study has some very significant implications for antiviral therapy in resource-limited settings, so I contacted my colleagues who work overseas, and they said that they are aware of this potential problem and are keeping an eye on it. Possible explanations offered by the investigators for this high rate of virologic failure were either pharmacokinetic issues with 3TC vs FTC (the latter having a longer half-life) or problems with giving nevirapine once daily. As you know, nevirapine extended-release formulation is now approved in the United States. But the third possibility that this is really confounded by indication. It's much more common for nevirapine to be prescribed to women of childbearing potential in place of efavirenz because efavirenz is a pregnancy category D drug and may be teratogenic.

I would be interested to hear your views on this: if you are using tenofovir 3TC/nevirapine or tenofovir FTC/nevirapine. What is your sense is about the effectiveness of this regimen? In the United States, this regimen is used infrequently, especially tenofovir 3TC/nevirapine, but before it is more widely used globally, we really should have a better sense of its efficacy.

Thanks very much for your attention, and I look forward to speaking with you next time.

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