全球首个二合一HIV维持疗法Juluca，获美国FDA批准上市
近日，美国食品和药物管理局（FDA）批准二合一HIV复方新药Juluca（dolutegravir/rilpivirine），作为一种维持治疗药物，用于已实现病毒抑制的HIV-1成人感染者的长期治疗。此次批准，使Juluca成为全球首个也是唯一一个二合一单片完整治疗方案。
Juluca是一种二合一复方单片，其中：
（1）dolutegravir是一种HIV整合酶链转移抑制剂（INSTI），已获美国和欧盟批准，其品牌名为Tivicay，由ViiV销售，该药适用于联合其他抗逆转录病毒药物，用于经治（既往已治疗过）、或初治（既往未接受治疗）HIV-1成人感染者以及体重至少30公斤的儿科感染者的治疗；
（2）rilpivirine是一种非核苷类逆转录酶抑制剂（NNRTI），通过阻断HIV基因组复制来发挥作用，该药是一种高活性的抗逆转录病毒治疗（HAART）药物，品牌名为Edurant，由强生旗下杨森子公司Janssen Sciences Ireland UC销售，该药适用于联合其他抗逆转录病毒药物，用于初治HIV-1成人感染者的治疗。
自20多年前，高效抗逆转录病毒药物问世以来，艾滋病已从一种致死性疾病转变为一种可控的慢性疾病。然而，艾滋病护理是一个长期过程，患者需要终生坚持治疗。目前，临床上一线治疗艾滋病的标准方案主要是三药方案，这种三药方案是将2种核苷类逆转录酶抑制剂（NRTI）与一种其他类别的药物联合用药。
Juluca的开发，旨在降低患者的药物暴露量、减少副作用并提高治疗依从性，同时保持高水平的疗效。Juluca的获批上市，将为广大HIV-1感染群体提供一种新的治疗选择，将大大简化艾滋病的一线治疗，并从根本上改变目前临床上的艾滋病治疗策略：一旦患者接受当前标准的3药或4药抗逆转录病毒方案治疗成功实现病毒学抑制后，即可转向Juluca二药方案进行长期治疗，这将大幅降低患者的每日服药量从而大幅提高治疗的依从性。
Juluca的获批，是基于III期临床项目SWORD的数据。该项目入组了超过1000例既往接受3药或4药（基于整合酶抑制剂、非核苷类逆转录酶抑制剂或蛋白酶抑制剂）抗逆转录病毒方案实现病毒学抑制的HIV-1感染者，评估了患者从3药或4药方案转向2药方案的疗效、安全性及耐受性。该项目包括2个III期临床研究（SWORD-1[NCT02429791]和SWORD-2[NCT02422797]），均为148周、随机、开放标签、非劣效性研究。这2个研究中，dolutegravir和rilpivirine均以单独的片剂服药，每日口服一次。

Juluca (Dolutegravir and Rilpivirine Tablets, for Oral Use)
FDA approval is for adults, who have HIV-1 RNA less than 50 copies per mL on a stable antiretroviral (ART) regimen for a minimum of six months, with no history of treatment failure and no known substitutions associated with resistance to the individual components of the HIV drug regimen.
The HIV drug regimen Juluca, which is intended to be taken as a single pill daily once, is a combination of ViiV Healthcare’s integrase strand transfer inhibitor dolutegravir 50mg and Janssen Therapeutics’ non-nucleoside reverse transcriptase inhibitor rilpivirine 25mg.
JULUCA Rx
Generic Name and Formulations:
Dolutegravir 50mg, rilpivirine 25mg; tabs.
Company:
Janssen Pharmaceuticals, Inc.
Indications for JULUCA:
A complete regimen for the treatment of HIV-1 infection in adults to replace the current antiretroviral regimen in those who are virologically suppressed (HIV-1 RNA <50 copies/mL) on a stable antiretroviral regimen for ≥6 months with no history of treatment failure and no known substitutions associated with resistance to the individual components of Juluca.
Adult:
Take with a meal. 1 tab once daily. Concomitant rifabutin: take additional rilpivirine 25mg tab once daily during coadministration.
Children:
Not established.
Contraindications:
Concomitant dofetilide, carbamazepine, oxcarbazepine, phenobarbital, phenytoin, rifampin, rifapentine, systemic dexamethasone (more than a single dose), St. John's wort, esomeprazole, lansoprazole, omeprazole, pantoprazole, rabeprazole.
Warnings/Precautions:
Discontinue immediately if severe skin or hypersensitivity reactions develop; monitor. Increased risk for worsening/development of elevated transaminases in patients with underlying hepatitis B or C; monitor for hepatotoxicity. Promptly evaluate if depressive symptoms occur. Severe renal impairment (CrCl <30mL/min) or ESRD: increase monitoring. Elderly. Pregnancy. Nursing mothers: not recommended.
Interactions:
See Contraindications. Concomitant other HIV-1 antiretroviral therapy: not recommended. May be affected by drugs that induce or inhibit UGT1A1, UGT1A3, UGT1A9, BCRP, and P-gp enzymes or transporters. May be antagonized by CYP3A inducers. May be potentiated by CYP3A inhibitors. Concomitant drugs with a known risk of Torsade de pointes: consider alternatives. May potentiate drugs eliminated via OCT2 or MATE1. Drugs that increase gastric pH may result in decreased plasma concentration. Concomitant antacids, cation-containing products, laxatives, sucralfate, oral iron/calcium supplements, and buffered drugs: give Juluca 4hrs before or 6hrs after. Separate H2-receptor antagonists by at least 4hrs before or 12hrs after. Limit concomitant metformin dose to 1000mg/day; adjust metformin dose when starting or stopping Juluca; monitor closely. May be potentiated by clarithromycin, erythromycin, telithromycin; consider alternatives (eg, azithromycin). Concomitant methadone; monitor.
Pharmacological Class:
HIV-1 integrase strand transfer inhibitor (INSTI) + non-nucleoside reverse transcriptase inhibitor.
Adverse Reactions:
Diarrhea, headache, insomnia, fatigue; immune reconstitution syndrome, lab abnormalities, hypersensitivity reactions, DRESS, hepatotoxicity, depressive disorders.
Note:
Register pregnant patients exposed to Juluca by calling (800) 258-4263.
Generic Availability:
NO
How Supplied:
Tabs—30