TAF / FTC批准：优点和限制在临床实践

StephenW

TAF/FTC Approved: Benefits and Limitations in Clinical Practice   

Paul E. Sax, MD

        
                     
         
    Hello. This is Dr Paul Sax from Brigham and Women's Hospital and Harvard Medical School. As you probably know, in early April the US Food and Drug Administration (FDA) approved the third tenofovir alafenamide coformulations for the treatment of HIV. This is tenofovir alafenamide plus emtricitabine, or TAF/FTC. The other two have been around for a bit longer. One is the rilpivirine FTC/TAF formulation, and the first one was, of course, the elvitegravir/cobicistat FTC/TAF formulation. Now those two are predominantly used for people who are just starting therapy or have never had treatment failure and are switching to it. But this TAF/FTC formulation could be used in a much broader patient population. As you are aware, there are many, many patients currently receiving TDF/FTC, both treatment-naive and treatment-experienced patients. So, arguably, this is the most important of the three approvals.
          All of the clinical studies done so far with TAF-based formulations have shown that TAF, compared with TDF, exerts less of an effect on bone density, is less likely to induce proteinuria—in particular, tubular proteinuria—and, thus far, there have not been any cases of renal disease directly attributed to TAF. There is a slight increase in lipids compared with TDF, and that is because tenofovir levels are so much lower with TAF than TDF. As a result, the lipid-lowering effect of tenofovir isn't seen quite as much. But all in all, TAF does appear to have better safety, and the signature toxicities of tenofovir disoproxil fumarate—renal toxicity and bone toxicity—appear to be diminished.
    In some circumstances, we want to be cautious about using TAF. We do not want to use it in patients who are receiving rifampin, either for treatment of tuberculosis or, as I had recently, a patient who needed rifampin for treatment of a Staphylococcus aureus infection. Rifampin significantly lowers TAF levels, and patients already have lower levels because of the fact that the dose is so much lower.
    A second area where we need to be cautious is in pregnancy. I do think that, ultimately, TAF/FTC during pregnancy would be a good option, but right now there are very limited data.
    The third area where I really caution people against using TAF/FTC is in preexposure prophylaxis. We have clinical trial data from TDF/FTC for preexposure prophylaxis; we have no comparable data for TAF/FTC. When studies had been done looking at tissue levels of tenofovir in patients who received TAF, they were significantly lower than with TDF. On the plus side, there has been a macaque model showing that TAF/FTC may help prevent infection during SIV challenge, but those are animal data. Clinical studies of TAF/FTC for PrEP really haven't been done.
    I do want to mention one final thing; it's a little pet peeve of mine. The FDA continues to include a black box warning for all nucleoside analogs about lactic acidosis and hepatic steatosis, and that's true about TAF/FTC as well. Thus far, as far as I'm aware, there have been no cases ever reported for this particular combination. If it's a class effect, it's got to be very, very rare with TAF/FTC. Second, it says that it's not approved for the treatment of hepatitis B. Recently, at the International Liver Congress, we did see data showing that TAF is as effective as TDF for the treatment of people with chronic hepatitis B. I would have no concerns about using TAF/FTC or any of the TAF-based formulations in patients who are hepatitis B–coinfected with HIV.
    That's a summary of some of the recent TAF approvals—in particular, the recent one of TAF/FTC. Thank you very much for listening.
   

StephenW

TAF / FTC批准：优点和限制在临床实践

保罗·萨克斯博士
披露| 5月20日，2016年
相关药品和疾病

    抗逆转录病毒治疗HIV感染
    HIV疾病
    及早对症HIV感染

你好。这是来自布莱根妇女医院和哈佛医学院的保罗·萨克斯博士。正如你可能知道，在四月初，美国食品和药物管理局（FDA）批准用于治疗HIV的第三替诺福韦alafenamide共配。这是替诺福韦alafenamide加上恩曲他滨，或TAF / FTC。另外两个已经存在的时间长一点。一个是rilpivirine FTC / TAF制剂，和第一个是，当然，elvitegravir / cobicistat FTC / TAF制剂。现在，这两个都是主要用于人谁刚开始治疗，或从未有过治疗失败，并切换到它。但是，这TAF / FTC配方可以在更广泛的患者人群中使用。如你所知，目前有收到TDF / FTC，两个治疗天真和治疗经验的患者很多，很多的患者。因此，可以说，这是最重要的三大批准。

所有与基于TAF-制剂迄今所做的临床研究已经表明，TAF与TDF相比，施加较少的对骨密度的效果，是不太可能诱导蛋白尿-尤其管状蛋白尿和，迄今为止，有尚未直接归因于TAF肾脏疾病的任何情况。有在脂质略有增加与TDF相比，这是因为替诺福韦水平如此低得多与TAF比TDF。其结果是，替诺福韦的降脂作用是没有看到相当多。但所有的一切，TAF确实出现有更好的安全性和替诺福韦的签名毒性富马酸肾毒性和骨毒性似乎减弱。

在某些情况下，我们要谨慎使用TAF。我们不希望谁正在接受利福平，无论是治疗结核病的病人使用它，或者，因为我有最近，谁需要利福平治疗金黄色葡萄球菌感染的病人。利福平显著降低TAF的水平，和患者已经因为这一事实，即所述剂量是如此之低更低的水平。

在这里我们需要保持谨慎的第二个领域是怀孕。我认为，最终，TAF / FTC在怀孕期间会是一个不错的选择，但现在也有非常有限的数据。

第三个方面，我真的告诫人们不要使用TAF / FTC在暴露前预防。我们有来自TDF / FTC用于暴露前预防的临床试验数据;我们有TAF / FTC没有可比数据。当研究已经做了看着谁收到TAF患者替诺福韦的组织水平，他们比TDF显著降低。从有利的一面，也一直表明TAF / FTC可能有助于防止SIV挑战，在感染猕猴模型，但这些动物实验数据。 TAF / FTC对PrEP的临床研究确实还没有完成。

我想提的最后一件事;这是我的一点忌讳。美国食品药物管理局继续包括黑匣子约乳酸性酸中毒和脂肪肝的所有核苷类似物的警告，这是关于TAF / FTC也是如此。到目前为止，据我所知，没有出现过报道过这个特殊的组合情况。如果它是一个类的效果，它必须是非常，非常罕见的与TAF / FTC。其次，它说，它没有批准用于乙型肝炎的治疗日前，在国际肝病大会上，我们确实看到的数据显示，TAF是TDF是有效的患有慢性乙型肝炎治疗我就没有顾虑关于谁是病人乙肝合并感染艾滋病毒使用TAF / FTC或任何基于TAF-配方。

这是一些最近的TAF的摘要认证 - 尤其，最近TAF / FTC之一。非常感谢您收听。

wangxinghao

   A second area where we need to be cautious is in pregnancy. I do think that, ultimately, TAF/FTC during pregnancy would be a good option, but right now there are very limited data.——数据虽然少，但是不是可以理解为，怀孕期间会推荐使用TAF呢？

csfluke

回复 wangxinghao 的帖子

论文里是说，现在关于怀孕期间使用TAF的数据很少，所以目前还需要很谨慎，但是认为TAF最终应该会是怀孕期间的好选择（这点我估计是因为基于TAF和TDF实际上是一样机理的药来推断出的，TDF已经认为是怀孕安全的了）。