2018年8月31日，默沙东HIV药物Delstrigo和Pifeltro获美国FDA批准用于既往未经历抗逆转录病毒治疗的成人患者。Delstrigo是一种日服一次的固定剂量复方药片，它由doravirine、拉米夫定和富马酸替诺福韦酯组成，而Pifeltro是一种新的非核苷类逆转录酶抑制剂（NNRTI），它由其它抗逆转录病毒药物组成。
  DELSTRIGO™和PIFELTRO™都用于治疗未接受过抗病毒疗法的成年HIV-1感染患者。
  在DRIVE-AHEAD试验中，728名无抗逆转录病毒治疗史的受试者被随机配给至少一剂量的 Delstrigo或每天一次的依法韦伦/恩曲他滨/富马酸替诺福韦酯（EFV/FTC/TDF）。
  结果显示，Delstrigo持续的病毒学抑制达到48周，达到了与EFV/FTC/TDF相比非劣效的主要终点（分另为84%和81%）。
  根据数据，21%的基线值有高病毒载量（HIV-1 RNA>100000拷贝/mL）的研究受试者中，77% 的Delstrigo治疗组受试者和72%的EFV/FTC/TDF治疗组受试者在48周时达到HIV-1 RNA<50 拷贝/mL。Delstrigo治疗组与EFV/FTC/TDF治疗组相比，因不良事件而导致的治疗中止率较低（分别为3%和6%），但前者不包含与治疗后急性乙肝感染加重相关的黑框警告。
  在DRIVE-FORWARD研究中，766名无抗逆转录病毒治疗史的受试者被随机配给每天至少一剂量的Pifeltro或每天一次的地瑞那韦+利托那韦（DRV+r），每名受试者由研究者有选择地搭配恩曲他滨（FTC/TDF或阿巴卡韦（ABC）/3TC。
  Pifeltro证明持续的病毒学抑制达到48周，达到与DRV+r基础方案相比非劣效的主要终点，两组分别有84%和80%的受试者其病毒学抑制达到HIV-1 RNA<50拷贝/mL。在20%的基线值有高病毒载量的研究受试者中，77%的 Pifeltro组受试者和74%的DRV+r组受试者在48周时达到HIV-1 RNA<50拷贝/mL。两组中因不良事件导致的治疗中止率均较低，Pifeltro治疗组为2%，DRV+r组为3%。
  由于在对抗艾滋病方面取得的显著进步，临床医生和患者可以有机会一起来确定最好针对每个患者的治疗方案，可考虑患者健康的其他方面，包括可能服用的其他药物，北卡罗来那大学教堂山医学院AIDS临床试验部感染疾病室Wohl教授称。Delstr和Pifeltro的获批在合适的无治疗成人患者中为HIV-1治疗提供了两种新的方案。

  Delstrigo以30支装/瓶装100mg/300mg/300mg强度的片剂。Pifeltro以30支装的瓶装成100mg强度的片剂。
FDA Approves Two New Oral Treatments for HIV-1 Infection
Merck announced that the Food and Drug Administration (FDA) has approved Delstrigo (doravirine, lamivudine, tenofovir disoproxil fumarate) fixed-dose tablets and Pifeltro (doravirine) tablets for the treatment of HIV-1 infection in appropriate patients.
Specifically, both Delstrigo and Pifeltro are indicated to treat HIV-1 infection in adults with no prior antiretroviral treatment experience. Delstrigo is approved as a complete regimen whereas Pifeltro is to be administered in combination with other antiretrovirals. Both medications are given once daily with or without food.
Delstrigo combines doravirine, a new non-nucleoside reverse transcriptase inhibitor (NNRTI), with lamivudine and tenofovir disoproxil fumarate, 2 nucleoside analogue reverse transcriptase inhibitors (NRTIs). It carries a Boxed Warning regarding post-treatment acute exacerbation of hepatitis B (HBV) infection.
The FDA approval was supported by data from the Phase 3, randomized, multicenter, double-blind, active-controlled trials, DRIVE-AHEAD (N=728) and DRIVE-FORWARD (N=766), which evaluated the safety and efficacy of Delstrigo and Pifeltro, respectively.
In DRIVE-AHEAD, treatment with Delstrigo demonstrated sustained viral suppression through 48 weeks, meeting its primary endpoint of non-inferior efficacy vs efavirenz/emtricitabine/tenofovir disoproxil fumarate (EFV/FTC/TDF). Viral suppression (HIV-1 RNA<50 copies/mL)was achieved in 84% of patients in the Delstrigo group vs 81% in the EFV/FTC/TDF group (treatment difference 3.5%, 95% CI, -2.0%, 9.0%). At week 48, Delstrigo-treated patients had statistically significant superior lipid profiles (changes in LDL and non-HDL cholesterol) compared with EFV/FTC/TDF.
n DRIVE-FORWARD, treatment with Pifeltro demonstrated sustained viral suppression through 48 weeks, meeting its primary endpoint of non-inferior efficacy vs darunavir + ritaonvir (DRV+r), each in combination with FTC/TDF or abacavir (ABC)/3TC. Viral suppression was achieved in 84% of patients in the Pifeltro group vs 80% in the DRV+r group (treatment difference 3.9%, 95% CI, -1.6%, 9.4%). At week 48, Pifeltro-treated patients had statistically significant superior lipid profiles (changes in LDL and non-HDL cholesterol) compared with DRV+r.
Delstrigo will be available as 100mg/300mg/300mg strength tablets in 30-count bottles. Pifeltro will be available as 100mg strength tablets in 30-count bottles. The Company anticipates both products to be available within 1 month.