Role of thymosin α1 in restoring immune response in immunological nonresponders living with HIV

Chen, Chaoyu1; Wang, Jiangrong1; Xun, Jingna1; Zhang, Xinyu1; Liu, Li1; Song, Zichen1; Zhang, Renfang1; Chen, Jun1; Lu, Hongzhou1,2

2024-01-17

10.1186/s12879-024-08985-y

BMC INFECTIOUS DISEASES   影响因子和分区

1471-2334

Background Immunological nonresponders (INRs) living with HIV are at increased risk of co-infection and multiple tumors, with no effective strategy currently available to restore their T-cell immune response. This study aimed to explore the safety and efficacy of thymosin alpha 1 in reconstituting the immune response in INRs.Methods INRs with CD4 + T cell counts between 100 and 350 cells/mu L were enrolled and received two-staged 1.6 mg thymosin alpha 1 subcutaneous injections for 24 weeks (daily in the first 2 weeks and biweekly in the subsequent 22 weeks) while continuing antiretroviral therapy. T cell counts and subsets, the expression of PD-1 and TIM-3 on T cells, and signal joint T cell receptor excision circles (sjTREC) at week 24 were evaluated as endpoints.Results Twenty three INRs were screened for eligibility, and 20 received treatment. The majority were male (19/20), with a median age of 48.1 years (interquartile range: 40.5-57.0) and had received antiretroviral therapy for 5.0 (3.0, 7.3) years. Multiple comparisons indicated that CD4 + T cell count and sjTREC increased after initiation of treatment, although no significant differences were observed at week 24 compared to baseline. Greatly, levels of CD4 + T cell proportion (17.2% vs. 29.1%, P < 0.001), naive CD4 + and CD8 + T cell proportion (17.2% vs. 41.1%, P < 0.001; 13.8% vs. 26.6%, P = 0.008) significantly increased. Meanwhile, the proportion of CD4 + central memory T cells of HIV latent hosts (42.7% vs. 10.3%, P < 0.001) significantly decreased. Moreover, the expression of PD-1 on CD4 + T cells (14.1% vs. 6.5%, P < 0.001) and CD8 + T cells (8.5% vs. 4.1%, P < 0.001) decreased, but the expression of TIM-3 on T cellsremained unaltered at week 24. No severe adverse events were reported and HIV viral loads kept stable throughout the study.Conclusions Thymosin alpha 1 enhance CD4 + T cell count and thymic output albeit as a trend rather than an endpoint. Importantly, it improves immunosenescence and decreases immune exhaustion, warranting further investigation.

HIV Immunological nonresponders Thymosin alpha 1 Immune response Thymic output

SCI

英语

通讯

Infectious Diseases

Infectious Diseases

WOS:001144630800002

BMC

IMMUNOLOGY

Web of Science

1.Fudan Univ, Shanghai Publ Hlth Clin Ctr, Caolang Rd 2901, Shanghai 201508, Peoples R China
2.Southern Univ Sci & Technol, Peoples Hosp Shenzhen 3, Affiliated Hosp 2, Natl Clin Res Ctr Infect Dis, Shenzhen 518112, Peoples R China

Chen, Chaoyu,Wang, Jiangrong,Xun, Jingna,et al. Role of thymosin α1 in restoring immune response in immunological nonresponders living with HIV[J]. BMC INFECTIOUS DISEASES,2024,24(1).

Chen, Chaoyu.,Wang, Jiangrong.,Xun, Jingna.,Zhang, Xinyu.,Liu, Li.,...&Lu, Hongzhou.(2024).Role of thymosin α1 in restoring immune response in immunological nonresponders living with HIV.BMC INFECTIOUS DISEASES,24(1).

Chen, Chaoyu,et al."Role of thymosin α1 in restoring immune response in immunological nonresponders living with HIV".BMC INFECTIOUS DISEASES 24.1(2024).