Role of thymosin α1 in restoring immune response in immunological nonresponders living with HIV.
BMC Infect Dis
; 24(1): 97, 2024 Jan 17.
Article
em En
| MEDLINE
| ID: mdl-38233816
ABSTRACT
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 α1 in reconstituting the immune response in INRs.METHODS:
INRs with CD4 + T cell counts between 100 and 350 cells/µL were enrolled and received two-staged 1.6 mg thymosin α1 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), naïve 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 α1 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. TRIAL REGISTRATION This single-arm prospective study was registered with ClinicalTrials.gov (NCT04963712) on July 15, 2021.Palavras-chave
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Infecções por HIV
/
Receptor Celular 2 do Vírus da Hepatite A
Tipo de estudo:
Observational_studies
/
Risk_factors_studies
Limite:
Adult
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Female
/
Humans
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Male
/
Middle aged
Idioma:
En
Revista:
BMC Infect Dis
Ano de publicação:
2024
Tipo de documento:
Article