Circulating immune and plasma biomarkers of time to HIV rebound in HIV controllers treated with vesatolimod.

Background

Antiretroviral therapy (ART) for HIV-1 treatment has improved lifespan but requires lifelong adherence for people living with HIV (PLWH), highlighting the need for a cure. Evaluation of potential cure strategies requires analytic treatment interruption (ATI) with close monitoring of viral rebound. Predictive biomarkers for HIV-1 rebound and/or duration of control during ATI will facilitate these HIV cure trials while minimizing risks. Available evidence suggests that host immune, glycomic, lipid, and metabolic markers of inflammation may be associated with HIV-1 persistence in PLWH who are treated during chronic HIV-1 infection.

Methods

We conducted

Results

Higher levels of CD69+CD8+ T-cells were consistently associated with shorter time to HIV-1 rebound at baseline and pre-ATI. With few exceptions, baseline fucosylated, non-galactosylated, non-sialylated, bisecting IgG N-glycans were associated with shorter time to HIV rebound and duration of control as with previous studies. Baseline plasma MPA and HPA binding glycans and non-galactosylated/non-sialylated glycans were associated with longer time to HIV rebound, while baseline multiply-galactosylated glycans and sialylated glycans, GNA-binding glycans, NPA-binding glycans, WGA-binding glycans, and bisecting GlcNAc glycans were associated with shorter time to HIV rebound and duration of control. Fourteen bioactive lipids had significant baseline associations with longer time to rebound and duration of control, and larger intact proviral HIV-1 DNA changes; additionally, three baseline bioactive lipids were associated with shorter time to first rebound and duration of control.

Conclusion

Consistent with studies in HIV non-controllers, proinflammatory glycans, lipids, and metabolites were generally associated with shorter duration of HIV-1 control. Notable differences were observed between HIV controllers vs. non-controllers in some specific markers. For the first time, exploratory biomarkers of ATI viral outcomes in HIV-controllers were investigated but require further validation.

Informations de copyright

Copyright © 2024 Abdel-Mohsen, Deeks, Giron, Hong, Goldman, Zhang, Huang, Verrill, Guo, Selzer, de Vries, Vendrame, SenGupta, Wallin and Cai.

Déclaration de conflit d'intérêts

SD reports grants from NIH; consulting fees from AbbVie, Eli Lilly, GlaxoSmithKline, and Immunocore; and stock in Enochian Biosciences and Tendel Therapies. LZ, SH, DV, SG, LS, CdV, EV, DS, JW, and YC report employment by and stock in Gilead Sciences, Inc. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. The authors declare that this study received funding from Gilead Sciences, Inc. The funder was involved in the study design, data collection, analysis and interpretation of data, preparation of the manuscript, and the decision to submit it for publication.