Plasma and antibody glycomic biomarkers of time to HIV rebound and viral setpoint.
AIDS
; 34(5): 681-686, 2020 04 01.
Article
em En
| MEDLINE
| ID: mdl-31972605
ABSTRACT
OBJECTIVE:
HIV cure research urgently needs to identify pre-analytic treatment interruption (ATI) biomarkers of time-to-viral-rebound and viral setpoint to mitigate the risk of ATI and accelerate development of a cure. We previously reported that galactosylated IgG glycans, G2, negatively correlate with cell-associated HIV DNA and RNA during antiretroviral therapy (ART). We hypothesized that this and other plasma glycomic traits can predict time-to-viral-rebound and viral setpoint upon ART cessation.DESIGN:
We profiled the circulating glycomes (plasma and bulk IgG) of two geographically distinct cohorts Philadelphia Cohort - 24 HIV-infected, ART-suppressed individuals who had participated in an open-ended ATI study without concurrent immunomodulatory agents. Johannesburg Cohort - 23 HIV-infected, ART-suppressed individuals who had participated in a 2-week ATI.METHODS:
Capillary electrophoresis and lectin microarray were used for glycomic analyses. Cox proportional-hazards model and log-rank test were used for statistical analyses.RESULTS:
Higher pre-ATI levels of the IgG glycan, G2, were significantly associated with a longer time-to-viral-rebound (hazard ratioâ=â0.12, Pâ=â0.05). In addition to G2, we identified several predictive glycomic traits in plasma, for example, levels of FA2BG1, a non-sialylated, core-fucosylated glycan, associated with a longer time-to-viral-rebound (hazard ratioâ=â0.023, Pâ=â0.05), whereas FA2G2S1, a sialylated glycan, associated with a shorter time-to-viral-rebound (hazard ratioâ=â24.1, Pâ=â0.028). Additionally, pre-ATI plasma glycomic signatures associated with a lower viral setpoint, for example, T-antigen (Galß1-3GalNAc) (râ=â0.75, Pâ=â0.0007), or a higher viral setpoint, for example, polylactosamine (râ=â-0.58, Pâ=â0.01). These results were initially validated in the Johannesburg Cohort.CONCLUSION:
We describe first-in-class, non-invasive, plasma and IgG glycomic biomarkers that inform time-to-viral-rebound and viral setpoint in two geographically distinct cohorts.
Texto completo:
1
Bases de dados:
MEDLINE
Assunto principal:
Infecções por HIV
/
HIV-1
/
Fármacos Anti-HIV
/
Terapia Antirretroviral de Alta Atividade
/
Glicômica
Tipo de estudo:
Prognostic_studies
Limite:
Humans
País/Região como assunto:
Africa
Idioma:
En
Revista:
AIDS
Assunto da revista:
SINDROME DA IMUNODEFICIENCIA ADQUIRIDA (AIDS)
Ano de publicação:
2020
Tipo de documento:
Article