FDA批准Truvada用于暴露前预防HIV-1感染

圣路易斯(MD Consult)——2012年7月16日，吉利德公司与美国食品药品管理局(FDA)宣布，已批准Truvada(恩曲他滨+富马酸替诺福韦酯)结合安全性行为，以降低高危成人(例如可能与已感染HIV的伴侣发生性行为的个体)经性行为感染人类免疫缺陷病毒1(HIV-1)的风险。Truvada将被用于暴露前预防(PrEP)，从而成为首个获得该适应证的药物。

支持Truvada获准用于PrEP的数据主要来自2项安慰剂对照试验。其中一项试验招募了2,499例HIV阴性的男性或变性女性，这些受试者均与男性存在性行为，并且有HIB感染高风险行为的证据，例如在与HIV阳性或状态不明的伴侣进行性行为时未坚持使用或根本不使用避孕套、有多名性伴侣、有卖淫行为等。结果显示，与安慰剂相比，使用Truvada可使HIV感染风险显著降低42%。预防效果与用药依从性密切相关。

另一项试验招募了4,758对异性夫妻，每对夫妻中都有1人感染了HIV而另1人未感染。研究者比较了Truvada+替诺福韦与安慰剂在预防HIV感染方面的疗效和安全性。结果显示，与安慰剂相比，使用Truvada可使感染风险降低75%。

在Truvada(联用依法韦仑)临床研究中报告的常见不良反应包括腹泻、恶心、疲乏、头痛、头晕、抑郁、失眠、异常梦境和皮疹。在采用Truvada进行PrEP的临床试验中，与使用Truvada相关的最常见不良反应包括头痛、腹部不适和体重下降。在合用Truvada与地达诺新、阿扎那韦和洛匹那韦/利托那韦时应谨慎，因为可能发生毒性。

在Truvada治疗过程中可能新发肾损害或原有肾损害加重，包括急性肾功能衰竭和范可尼综合征。应当在使用Truvada之前计算肌酐清除率。Truvada不得与肾毒性药物合用，如果最近曾使用肾毒性药物也须禁用Truvada。

在批准Truvada的同时，FDA强调了该产品的黑框警告，提醒医务人员和未感染者，将Truvada用于PrEP仅限于HIV确定为阴性的个体。在使用Truvada期间必须每3个月复查以确定HIV仍为阴性，从而降低诱发耐药性HIV-1变异株的风险。HIV阳性或状态不明者不得将该药用于PrEP。

作为风险评估与降低策略(REMS)的一部分，吉利德公司准备了一些材料用于教育和告知医务人员和未感染者如何采用Truvada进行PrEP。这些材料还强调必须严格依据说明书给药，而且Truvada只是HIV感染综合性预防策略的一部分，采用Truvada进行PrEP仅限于HIV确定为阴性的个体，并建议在治疗期间至少每3个月进行1次HIV-1筛查。如果临床症状或体征提示存在急性HIV-1感染，则不得使用Truvada进行PrEP。

Truvada最初于2004年获准与其他抗逆转录病毒药物联用，用于治疗成人HIV-1感染。

爱思唯尔  版权所有

ST LOUIS (MD Consult) - On July 16, 2012, Gilead and the US Food and Drug Administration (FDA) announced the approval of Truvada (emtricitabine and tenofovir disoproxil fumarate), in combination with safer sex practices, to reduce the risk of sexually acquired human immunodeficiency virus-1 (HIV-1) infection in adults at high risk, such as persons who may engage in sexual activity with HIV-infected partners. Truvada is to be used for preexposure prophylaxis (PrEP). It is the first drug approved for this indication.

Data supporting the approval of Truvada for PrEP came primarily from 2 placebo-controlled trials. In one trial, the use of Truvada was evaluated in 2499 HIV-negative men or transgender women who have sex with men and with evidence of high-risk behavior for HIV infection, such as inconsistent or no condom use during sex with a partner of positive or unknown HIV status, a high number of sex partners, and exchange of sex for commodities. Results showed that the use of Truvada was effective in reducing the risk of HIV infection by 42% compared with placebo. Efficacy was strongly correlated with drug adherence in this trial.

The other trial was conducted in 4758 heterosexual couples where one partner was HIV-infected and the other was not. The trial evaluated the efficacy and safety of Truvada and tenofovir versus placebo in preventing HIV infection in the uninfected male or female partner. Results showed that the use of Truvada reduced the risk of becoming infected by 75% compared with placebo.

Common adverse effects reported during clinical studies with Truvada (in combination with efavirenz) include diarrhea, nausea, fatigue, headache, dizziness, depression, insomnia, abnormal dreams, and rash. In clinical trials of Truvada for PrEP, the most common adverse effects associated with Truvada use were headache, abdominal discomfort, and weight loss. Caution should be exercised when coadministering Truvada with didanosine, atazanavir, and lopinavir/ritonavir because of the potential for toxicity.

New onset or worsening of renal impairment may occur during treatment with Truvada, including acute renal failure and Fanconi Syndrome. Creatinine clearance should be calculated before administering Truvada. Truvada should not be administered concurrently with or with recent use of nephrotoxic drugs.

With this new approval of Truvada, the FDA is strengthening the product's Boxed Warning to alert health care professionals and uninfected persons that the use of Truvada for PrEP must only be used by persons whose HIV status is confirmed as negative before the drug is initiated. Testing and confirmation of negative HIV status is necessary every 3 months during the use of Truvada to reduce the risk of development of resistant HIV-1 variants. The drug is contraindicated for PrEP in persons with unknown or positive HIV status.

As part of a Risk Evaluation and Mitigation Strategy developed by Gilead and the FDA to ensure the safe use of Truvada for PrEP, Gilead has developed materials to educate and inform health care providers and uninfected persons about the use of Truvada for PrEP. These materials highlight the importance of strict adherence to the dosing regimen, emphasize that Truvada must be considered as only 1 part of a comprehensive prevention strategy to reduce the risk of HIV-1 infection, convey that Truvada for PrEP should only be used in persons with confirmed HIV negative status, and advise that HIV-1 screening should be repeated at least every 3 months while taking Truvada for PrEP. Truvada for PrEP should not be initiated when clinical signs or symptoms consistent with acute HIV-1 infection are present.

Truvada was originally approved in 2004 in combination with other antiretroviral agents as a treatment for HIV-1 infection in adults.