Ontology highlight
ABSTRACT:
Methods: We recruited Malawian adults with CD4 <100 cells/?L 2 weeks after starting ART in the REALITY trial (NCT01825031). Carotid femoral pulse-wave velocity (cfPWV) measured arterial stiffness 2, 12, 24, and 42 weeks post-ART initiation. Plasma inflammation markers were measured by electrochemiluminescence at weeks 2 and 42. Hierarchical clustering on principal components identified inflammatory clusters.
Results: 211 participants with HIV grouped into 3 inflammatory clusters representing 51 (24%; cluster-1), 153 (73%; cluster-2), and 7 (3%; cluster-3) individuals. Cluster-1 showed markedly higher CD4 and CD8 T-cell expression of HLADR and PD-1 versus cluster-2 and cluster-3 (all P < .0001). Although small, cluster-3 had significantly higher levels of cytokines reflecting inflammation (IL-6, IFN-?, IP-10, IL-1RA, IL-10), chemotaxis (IL-8), systemic and vascular inflammation (CRP, ICAM-1, VCAM-1), and SAA (all P < .001). In mixed-effects models, cfPWV changes over time were similar for cluster-2 versus cluster-1 (relative fold-change, 0.99; 95% CI, .86-1.14; P = .91), but greater in cluster-3 versus cluster-1 (relative fold-change, 1.45; 95% CI, 1.01-2.09; P = .045).
Conclusions: Two inflammatory clusters were identified: one defined by high T-cell PD-1 expression and another by a hyperinflamed profile and increases in cfPWV on ART. Further clinical characterization of inflammatory phenotypes could help target vascular dysfunction interventions to those at highest risk.
Clinical trials network: NCT01825031.
SUBMITTER: Kelly C
PROVIDER: S-EPMC7713681 | biostudies-literature | 2020 Dec
REPOSITORIES: biostudies-literature
Kelly Christine C Tinago Willard W Alber Dagmar D Hunter Patricia P Luckhurst Natasha N Connolly Jake J Arrigoni Francesca F Abner Alejandro Garcia AG Kamngona Ralph R Sheha Irene I Chammudzi Mishek M Jambo Kondwani K Mallewa Jane J Rapala Alicja A Heyderman Robert S RS Mallon Patrick W G PWG Mwandumba Henry H Walker A Sarah AS Klein Nigel N Khoo Saye S
Clinical infectious diseases : an official publication of the Infectious Diseases Society of America 20201201 9
<h4>Background</h4>Inflammation drives vascular dysfunction in HIV, but in low-income settings causes of inflammation are multiple, and include infectious and environmental factors. We hypothesized that patients with advanced immunosuppression could be stratified into inflammatory phenotypes that predicted changes in vascular dysfunction on ART.<h4>Methods</h4>We recruited Malawian adults with CD4 <100 cells/μL 2 weeks after starting ART in the REALITY trial (NCT01825031). Carotid femoral pulse- ...[more]