Biktarvy(bictegravir, emtricitabine, tenofovir alafenamide)为每日一次的单片疗法,治疗HIV-1感染
近日，Gilead Sciences宣布，美国FDA批准了其新药Biktarvy上市，作为每日一次的单片片剂疗法，治疗HIV-1感染。
Biktarvy由bictegravir（50mg）、emtricitabine（200mg）、与tenofovir alafenamide（25mg）三种成分组成。与Gilead的另一款抗HIV药物Descovy（FTC/TAF）相比，Biktarvy多了bictegravir这个成分。这是一款全新的无助推（unboosted）整合酶链转移抑制剂（INSTI）。
这款新药的疗效与安全性在4项正在进行的3期临床试验中得到了验证。试验1489和1490招募的是初治的HIV-1感染成人患者，而试验1844与1878则招募了病毒感染在病毒学上得到抑制的成人患者。这几项研究一同招募了2415名志愿者，涵盖不同的年龄与种族。综合这4项研究来看，Biktarvy抵达了非劣效性的主要临床终点。
具体来看，在试验1489中，629名患者以1：1的比例分为两组，分别接受Biktarvy与abacavir/dolutegravir/lamivudine（600/50/300mg）的治疗。在48周后，这两组患者中，分别有92.4%和93.0%的患者达到了HIV-1 RNA小于每毫升50c的主要终点。而在试验1490中，645名患者接受的分别是Biktarvy与dolutegravir/FTC/TAF。同样，两组达到主要终点的比例接近，分别为89.4%与92.9%。
在试验1878中，577名在药物作用下，HIV-1 RNA已经小于每毫升50c的成人患者被1：1分为两组，一组继续现有的疗法，另一组则切换到Biktarvy的治疗。在48周后，两组中均有1.7%的患者其HIV-1 RNA回到不低于每毫升50c的水平；而根据FDA的算法，分别有92.1%（Biktarvy组）与88.9%（现有疗法组）的患者保持了HIV-1 RNA小于每毫升50c。这些结果表明了Biktarvy的非劣效性。试验1844的结果将在今年晚些时候的科学会议上公开。
“在为期48周的临床试验里，没有一名使用bictegravir加FTC/TAF的患者发展出治疗中出现的抵抗。无论是初治的患者，还是已经在病毒学上得到抑制的患者，都展现出了这个结果，” 布莱根妇女医院（Brigham and Women’s Hospital）的传染病部临床主任Paul Sax博士说道：“此外，临床数据还表明其抗病毒的有效性、耐受性、以及有限的药物相互作用，能为广泛的HIV感染人群提供有效的新治疗方案。”
“Gilead承诺改善HIV感染患者的治疗，简化疗法。我们将继续投资下一代的疗法，这包括那些有望治愈HIV患者的疗法，” Gilead的总裁兼首席执行官John F. Milligan博士说道：“我们很高兴能提供最新的三联疗法Biktarvy，将整合酶抑制剂与最常处方的双重NRTI骨架药物一起整合到单片片剂疗法中。”并期待它能为诸多HIV感染者带来新的治疗选择，控制他们的病情。

BIKTARVY(bictegravir, emtricitabine, tenofovir alafenamide)
BIKTARVY Rx
Generic Name and Formulations:
Bictegravir 50mg, emtricitabine 200mg, tenofovir alafenamide 25mg; tabs.
Company:
Gilead Sciences, Inc
Monograph added.
Indications for BIKTARVY:
A complete regimen for the treatment of HIV-1 infection in adults with no antiretroviral treatment history or to replace the current antiretroviral regimen in those who are virologically suppressed (HIV-1 RNA <50 copies/mL) on a stable antiretroviral regimen for ≥3 months with no history of treatment failure and no known substitutions associated with resistance to the individual components of Biktarvy.
Adult:
Test for HBV infection prior to initiation. 1 tab once daily.
Children:
<18yrs: not established.
Contraindications:
Concomitant dofetilide, rifampin.
Warnings/Precautions:
Test for HBV before starting therapy and closely monitor patients co-infected with HBV and HIV for several months after stopping treatment (discontinuing therapy may exacerbate HBV infection); if appropriate, anti-hepatitis B therapy may be warranted (esp. in those with advanced liver disease or cirrhosis). Suspend therapy if lactic acidosis or hepatotoxicity (eg, hepatomegaly, steatosis) occurs. Monitor serum creatinine, CrCl, urine glucose, urine protein, and serum phosphorus (in patients at risk for chronic renal disease); discontinue if significant renal dysfunction or Fanconi syndrome occurs. Severe renal impairment (CrCl <30mL/min): not recommended. Severe hepatic impairment (Child-Pugh Class C): not recommended. Pregnancy. Nursing mothers: not recommended.
Interactions:
See Contraindications. Concomitant other antiretrovirals: not recommended. May potentiate concomitant OCT2 and MATE1 substrates (eg, dofetilide). May be affected by drugs that induce or inhibit CYP3A and UGT1A1. Concomitant drugs that strongly affect P-gp and BCRP activity may lead to changes in TAF absorption. May be potentiated by drugs that decrease renal function or compete for active tubular secretion (eg, acyclovir, cidofovir, ganciclovir, valacyclovir, valganciclovir, aminoglycosides, NSAIDs). May be antagonized by anticonvulsants (eg, carbamazepine, oxcarbazepine, phenobarbital, phenytoin); consider alternatives. Concomitant rifabutin, rifapentine, St. John's wort: not recommended. Concomitant cation-containing antacids, laxatives, sucralfate, and buffered drugs: give Biktarvy 2hrs before. Concomitant oral iron/calcium supplements: may take together with food. Routine coadministration with, or 2hrs after, cation-containing antacids or oral iron/calcium supplements: not recommended. May potentiate metformin (refer to metformin labeling).
Pharmacological Class:
HIV-1 integrase strand transfer inhibitor (INSTI) + nucleoside analog reverse transcriptase inhibitors (NRTIs).
Adverse Reactions:
Diarrhea, nausea, headache; HBV exacerbation, new onset or worsening renal impairment, immune reconstitution syndrome, lactic acidosis, hepatomegaly.
Note:
Register pregnant patients in the Antiretroviral Pregnancy Registry (APR) by calling (800) 258-4263.
Generic Availability:
NO
How Supplied:
Tabs—30