Abstract:
Over 80% of people living with HIV in low-and-middle-income countries (LMICs) take first-line TDF/XTC/DTG (TLD). Due to hard-fought activism, in >100 LMICs TLD now costs under $45pppy under Voluntary License. With final DTG patents expiring by 2029, generic TLD will soon be available globally. We identify seven critical benchmarks underpinning TLDs success which novel ART should now meet, and an eighth for which novel ART should aim. These are superior efficacy; a high genetic barrier to resistance; safety in hepatitis B coinfection; favourable drug-drug interaction profiles including with antimycobacterials; efficacy in HIV-2; safety in pregnancy, long-acting formulation availability and affordable pricing from the outset. We illustrate when generic TLD will become available worldwide and compare this with trial programmes and approval timelines for two case-study novel ART combinations: islatravir/doravirine and cabotegravir/rilpivirine. We demonstrate that currently these regimens and trial programmes will not meet key benchmarks required to compete with TLD.
摘要:
在中低收入国家(LMICs),超过80%的艾滋病毒感染者使用一线TDF/XTC/DTG(TLD)。由于艰苦奋斗的激进主义,在>100个LMICsTLD中,根据自愿许可,TLD的成本低于45美元。随着最终的DTG专利将于2029年到期,通用TLD将很快在全球上市。我们确定了七个关键基准,支撑新的ART现在应该达到的TLD成功,以及小说艺术应该瞄准的第八个目标。这些都是优越的疗效;高遗传屏障的耐药性;在乙型肝炎合并感染的安全性;有利的药物-药物相互作用概况,包括与抗菌药;在HIV-2的功效;在怀孕期间的安全性,从一开始就提供长效制剂和负担得起的价格。我们说明了通用TLD何时在全球范围内上市,并将其与两种病例研究新型ART组合的试验计划和批准时间表进行了比较:islatravir/doravirine和cabotegravir/rilpivirine。我们证明,目前这些方案和试验计划无法满足与TLD竞争所需的关键基准。