近日，美国食品和药物管理局批准了一种新型艾滋病药物Dovato（dolutegravir/lamivudine） 治疗方案上市，是针对从未接受抗逆转录病毒治疗的艾滋病毒感染患者的首个双药治疗方案。
此次批准的治疗方案名为Dovato（dolutegravir和lamivudine），作为治疗成人人类免疫缺陷病毒1型（HIV-1）感染的完整方案，该方案用于没有抗逆转录病毒治疗史，且没有与之相关的已知或疑似替代对Dovato各个组成部分的抵制。
Dovato 是FDA批准的第一个针对HIV感染成年人的双药剂型，固定剂量的治疗完整方案
Dovato（dolutegravir和lamivudine）是一种每日一次，单药，双药治疗方案的批准药物dolutegravir（Tivicay）和拉米夫定（Epivir）用于治疗成人中没有抗逆转录病毒（ARV）的HIV-1感染和度鲁特韦/拉米夫定。
批准日期：2019年4月9日  研发公司：ViiV Healthcare
DOVATO（度鲁特韦/拉米夫定[dolutegravir/lamivudine]）片剂，用于口服
美国最初批准：2019年
警告：感染乙型肝炎病毒（HBV）和人类免疫缺陷病毒（HIV-1）的患者：抗HBV的HBV和乙型肝炎病毒的出现
查看完整的盒装警告的完整处方信息。
所有HIV-1患者应在开始DOVATO之前进行HBV检测。已经报道了与含拉米夫定的抗逆转录病毒方案相关的拉米夫定耐药性HBV变异株的出现。如果DOVATO用于共感染HIV-1和HBV的患者，则应考虑进一步治疗以适当治疗慢性HBV;否则，考虑另一种方案。
据报道，感染HIV-1和HBV并且停用了拉米夫定（DOVATO的组成部分）的患者出现了严重的HBV急性加重期。密切监测这些患者的肝功能，并在适当的情况下，开始抗HBV治疗。
作用机制
DOVATO是HIV-1抗逆转录病毒药物dolutegravir和amlamudine的固定剂量组合[见微生物学]。
适应症和用法
DOVATO，一种双药物组合的dolutegravir（整合酶链转移抑制剂[INSTI]）和拉米夫定（核苷类似物逆转录酶抑制剂[NRTI]）被指示为治疗成人人类免疫缺陷病毒1型（HIV-1）感染的完整方案没有抗逆转录病毒治疗史且没有已知的取代与DOVATO的各个组分的抗性相关。
剂量和给药
•在开始DOVATO之前或之时，测试患者是否感染HBV。
•妊娠试验：在有生育能力的个体中开始使用DOVATO之前进行妊娠试验。
•每天一次口服一片，有或没有食物。
•当与卡马西平或利福平合用时，DOVATO中的dolutegravir剂量（50 mg）不足。如果DOVATO与卡马西平或利福平共同给药，每日一次服用一片DOVATO，然后再服用50毫升的dolutegravir，距离DOVATO剂量约12小时。
剂量形式和强度
片剂：50mg的dolutegravir和300mg的拉米夫定。
禁忌症
•先前对dolutegravir或拉米夫定的超敏反应。
•与多非利特共同给药。
警告和注意事项
•dolutegravir报道了以皮疹，体质发现，有时器官功能障碍（包括肝损伤）为特征的过敏反应。如果出现过敏反应的症状症状，立即停用DOVATO，因为停止治疗的延迟可能导致危及生命的反应。
•接受过白内障患者的患者报告有肝毒性。患有潜在乙型肝炎或丙型肝炎的患者可能因DOVATO而恶化或发生转氨酶升高的风险增加。建议监测肝毒性。
•在怀孕和怀孕初期使用时可能会发生胚胎 - 胎儿毒性。由于存在神经管缺陷的风险，在怀孕的前三个月受孕时避免使用DOVATO。建议有生育能力的人使用有效的感染。
•使用核苷类似物报道了乳酸性酸中毒和伴有脂肪变性的严重肝肿大。
•据报道，联合抗逆转录病毒疗法治疗的患者存在免疫重建综合征。
不良反应
在≥2％（接受DOVATO的人）中观察到的最常见的不良反应（所有等级）是头痛，腹泻，恶心，失眠和疲劳。
要报告疑似不良反应，请致电1-877-844-8872联系ViiVHealthcare，或致电1-800-FDA-1088或www.fda.gov/medwatch联系FDA。
药物相互作用
•DOVATO是一种治疗HIV-1感染的完整方案;因此，不建议与其他抗逆转录病毒药物联合用于治疗HIV-1感染。
•请参阅重要药物相互作用的完整处方信息
与DOVATO。
用于特定人群
•怀孕：由于存在神经管缺陷的风险，在妊娠早期怀孕时避免使用DOVATO。
•哺乳期：由于有可能进行HIV-1传播，因此不推荐母乳喂养。
•具有生殖潜力的女性和男性：建议对有生育能力的个体进行妊娠试验和接受治疗。
•肾功能损害：不推荐患有DOVATO的患者肌酐清除率小于50 mL/min。
•肝功能损害：严重肝功能不全患者不建议使用DOVATO（Child-Pugh评分C）。
包装提供/存储和处理
每片DOVATO片剂含有50毫克dolutegravir作为dolutegravir钠和300mglamlamivine，是一种椭圆形，双凸面，白色薄膜包衣片剂，单面上印有“SV 137”。
装有儿童防护罩的30片装NDC 49702-246-13。
储存在30C（86F）以下。
完整说明书附件：
https://www.gsksource.com/pharma/content/dam/GlaxoSmithKline/US/en/Prescribing_
Information/Dovato/pdf/DOVATO-PI-PIL.PDF
Dovato(dolutegravir/lamivudine)tablets
US Food and Drug Administration (FDA) approved Dovato, a complete, once-daily, single-tablet regimen of dolutegravir (DTG) 50 mg and lamivudine (3TC) 300 mg for the treatment of HIV-1 infection in adults with no antiretroviral (ARV) treatment history and with no known resistance to either DTG or 3TC. Dovato, a two-drug regimen (2DR), reduces exposure to the number of ARVs from the start of treatment, while still maintaining the efficacy and high barrier to resistance of a traditional DTG-based three-drug regimen.
Deborah Waterhouse, CEO, ViiV Healthcare, said: “Building on our innovative portfolio of medicines, Dovato is powered by dolutegravir, an antiretroviral included in multiple combination therapies and the most prescribed integrase inhibitor in the world, 2 coupled with the established profile of lamivudine. With Dovato, the first complete, single-tablet, two-drug regimen for treatment-naïve adults, ViiV Healthcare is delivering what patients are requesting—a chance to treat their HIV-1 infection with as few drugs as possible, marking a significant step in HIV treatment.”
IMPORTANT SAFETY INFORMATION (ISI)
The following ISI is based on the Highlights section of the Prescribing Information for Dovato. Please consult the full Prescribing Information for all the labeled safety information for Dovato.
WARNING: PATIENTS CO-INFECTED WITH HEPATITIS B VIRUS (HBV) AND HUMAN IMMUNODEFICIENCY VIRUS (HIV-1): EMERGENCE OF LAMIVUDINE-RESISTANT HBV AND EXACERBATIONS OF HBV
All patients with HIV-1 should be tested for the presence of HBV prior to or when initiating DOVATO. Emergence of lamivudine-resistant HBV variants associated with lamivudine-containing antiretroviral regimens has been reported. If DOVATO is used in patients co-infected with HIV-1 and HBV, additional treatment should be considered for appropriate treatment of chronic HBV; otherwise, consider an alternative regimen.
Severe acute exacerbations of HBV have been reported in patients who are co-infected with HIV-1 and HBV and have discontinued lamivudine, a component of DOVATO. Closely monitor hepatic function in these patients and, if appropriate, initiate anti-HBV treatment
DOSAGE AND ADMINISTRATION
Prior to or when initiating DOVATO, test patients for HBV infection.
Pregnancy Testing: Perform pregnancy testing before initiation of DOVATO in individuals of childbearing potential.
One tablet taken orally once daily with or without food.
The dolutegravir dose (50 mg) in DOVATO is insufficient when coadministered with carbamazepine or rifampin. If DOVATO is coadministered with carbamazepine or rifampin, take one tablet of DOVATO once daily, followed by an additional dolutegravir 50-mg tablet, approximately 12 hours from the dose of DOVATO.
CONTRAINDICATIONS
Prior hypersensitivity reaction to dolutegravir or lamivudine.
Coadministration with dofetilide.
WARNINGS AND PRECAUTIONS
Hypersensitivity reactions characterized by rash, constitutional findings, and sometimes organ dysfunction, including liver injury, have been reported with dolutegravir. Discontinue DOVATO immediately if signs or symptoms of hypersensitivity reactions develop, as a delay in stopping treatment may result in a life-threatening reaction.
Hepatotoxicity has been reported in patients receiving a dolutegravir-containing regimen. Patients with underlying hepatitis B or C may be at increased risk for worsening or development of transaminase elevations with DOVATO. Monitoring for hepatotoxicity is recommended.
Embryo-fetal toxicity may occur when used at the time of conception and in early pregnancy. Avoid use of DOVATO at the time of conception through the first trimester of pregnancy due to the risk of neural tube defects. Advise individuals of childbearing potential to use effective contraception.
Lactic acidosis and severe hepatomegaly with steatosis, including fatal cases, have been reported with the use of nucleoside analogues.
Immune reconstitution syndrome has been reported in patients treated with combination antiretroviral therapy.
ADVERSE REACTIONS
The most common adverse reactions (all grades) observed in ≥2% (in those receiving DOVATO) were headache, diarrhea, nausea, insomnia, and fatigue.
DRUG INTERACTIONS
DOVATO is a complete regimen for the treatment of HIV-1 infection; therefore, coadministration with other antiretroviral drugs for the treatment of HIV-1 infection is not recommended.
Refer to the full prescribing information for important drug interactions with DOVATO.
USE IN SPECIFIC POPULATIONS
Pregnancy: Avoid use of DOVATO at the time of conception through the first trimester due to the risk of neural tube defects.
Lactation: Breastfeeding is not recommended due to the potential for HIV-1 transmission.
Females and males of reproductive potential: Pregnancy testing and contraception are recommended in individuals of childbearing potential.
Renal Impairment: DOVATO is not recommended in patients with creatinine clearance less than 50 mL/min.
Hepatic Impairment: DOVATO is not recommended in patients with severe hepatic impairment (Child-Pugh Score C).