Introduction: Ending the HIV epidemic will likely require an efficacious preventative HIV vaccine. As vaccine development progresses, new challenges emerge in the context of an evolving prevention landscape.Areas covered: The progress in HIV vaccine development including trial regimens, results, and impact of pre-exposure prophylaxis (PrEP) including trial design.Expert opinion: Building upon the modest RV144 efficacy results, a follow-up study was launched in South Africa using modified vaccine constructs, ALVAC-HIV vector and gp120 protein boosts (Clade C strains). An adjuvant, MF59, was used to improve durability. Another Phase 2b regimen using an Adenovirus-26 vector with multivalent mosaic antigen inserts and a Clade C gp140 boost advanced into efficacy testing. Current vaccine efficacy studies enroll participants at risk for HIV, offer robust prevention packages, and notably do not restrict PrEP usage. With increasingly efficacious prevention options, future clinical trial designs become more complex. While formally requiring PrEP in HIV vaccine trials (e.g. PrEP ± Vaccine) may maximize protection, it raises both ethical and incremental efficacy over PrEP. Increasing vaccine complexity may lead to persistent vaccine-induced seropositivity, which presents different challenges. Discussion with the community and broader stakeholder engagement will help create solutions to these challenges.

中文翻译：

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预防性HIV疫苗：临床试验中的疫苗方案和潜在挑战。

简介：结束艾滋病毒流行可能需要有效的预防性艾滋病毒疫苗。随着疫苗开发的进展，在不断变化的预防形势下出现了新的挑战，涉及的领域包括：HIV疫苗开发的进展，包括试验方案，结果以及包括试验设计在内的暴露前预防（PrEP）的影响专家意见：根据适度的RV144功效结果，南非在南非开展了一项后续研究，使用了改良的疫苗构建体，ALVAC-HIV载体和gp120蛋白增强剂（进化枝C株）。佐剂MF59用于改善耐久性。使用带有多价花叶抗原插入片段和Clade C gp140增强的Adenovirus-26载体的另一2b期方案已进入功效测试。目前的疫苗功效研究招募了有感染HIV风险的参与者，提供强大的防护包，尤其不要限制PrEP的使用。随着越来越有效的预防选择，未来的临床试验设计变得更加复杂。虽然在HIV疫苗试验中正式要求使用PrEP（例如PrEP±疫苗）可以最大程度地提高保护水平，但与PrEP相比，它在道德和疗效上都提高了。疫苗复杂性的增加可能导致持续的疫苗诱导的血清阳性，这带来了不同的挑战。与社区进行讨论并扩大利益相关者的参与将有助于为这些挑战提供解决方案。与PrEP相比，它可以提高道德和增量效力。疫苗复杂性的增加可能导致持续的疫苗诱导的血清阳性，这带来了不同的挑战。与社区进行讨论并扩大利益相关者的参与将有助于为这些挑战提供解决方案。与PrEP相比，它可以提高道德和增量效力。疫苗复杂性的增加可能导致持续的疫苗诱导的血清阳性，这带来了不同的挑战。与社区进行讨论并扩大利益相关者的参与将有助于为这些挑战提供解决方案。