HLA-mismatched allogeneic adoptive immune therapy in patients with severely immunosuppressed AIDS: a multicenter, open-label, controlled, phase 2a study.
Tao YangZhiman XieZhe XuBo TuHuan LuHuihuang HuangLei HuangChao ZhangLiying GaoLei JinPing MaJun ZouLimin LiuCheng ZhenChunbao ZhouSirun MengYuan-Yuan LiJin-Wen SongShixiong YangHui-Sheng AiYan-Mei JiaoMing ShiRuonan XuFu-Sheng WangPublished in: Emerging microbes & infections (2024)
Recurrent opportunistic infections (OIs) in patients with severely immunosuppressed AIDS remain an unresolved medical challenge despite advancements in antiretroviral therapy (ART). To address this gap, we developed an HLA-mismatched allogeneic adoptive immune therapy (AAIT) specifically targeting this patient population. The safety and efficacy of this novel therapeutic approach were preliminarily confirmed in our phase 1 trial. Subsequently, a multicenter, open-label, controlled, phase 2a trial was conducted to evaluate the efficacy of AAIT in combination with ART compared with the conventional ART-only regimen. No difference in the incidence of adverse events (AEs) was observed between the two groups at the 96-week follow-up. AAIT treatment improved CD4+ T cell recovery at weeks 72 ( P = 0.048) and 96 ( P = 0.024) compared to the Control Group. Additionally, stratified analysis of patients in the AAIT Group showed that donor/recipient sex mismatch was significantly associated with the likelihood of patients achieving an immunological response (OR = 8.667; 95% CI, 2.010-37.377; P = 0.004). These findings suggest that AAIT serves as a promising adjunct therapy for improving the outcomes of patients with severely immunosuppressed AIDS. Further studies are needed to elucidate the immunological mechanisms underlying AAIT and identify the subpopulations that respond optimally to this therapeutic approach. This trial is registered at www.clinicaltrials.gov (NCT04098770). Trial registration: ClinicalTrials.gov identifier: NCT04098770. Trial registration: ClinicalTrials.gov identifier: NCT02651376.
Keyphrases
- antiretroviral therapy
- phase iii
- open label
- phase ii
- hiv infected
- study protocol
- clinical trial
- human immunodeficiency virus
- hiv infected patients
- hiv positive
- hiv aids
- stem cell transplantation
- bone marrow
- cell therapy
- double blind
- healthcare
- phase ii study
- risk factors
- high dose
- adipose tissue
- case report
- south africa
- mesenchymal stem cells
- cross sectional
- squamous cell carcinoma
- cancer therapy
- patient reported
- weight loss
- glycemic control