HIV-1 infection induces a chronic inflammatory environment not restored by suppressive antiretroviral therapy (ART). As of today, the effect of viral suppression and immune reconstitution in people living with HIV-1 (PLWH) has been well described but not completely understood. Herein, we show how PLWH who naturally control the virus (PLWHEC) have a reduced proportion of CD4+CCR6+ and CD8+CCR6+ cells compared to PLWH on suppressive ART (PLWHART) and HIV-1 negative controls (HC). Expression of CCR2 was reduced on both CD4+, CD8+ and classical monocytes in PLWHEC compared to PLWHART and HC. Longer suppressive therapy, measured in the same patients, decreased number of cells expressing CCR2 on all monocytic cell populations while expression on CD8+ T cells increased. Furthermore, the CD4+CCR6+/CCR6- cells exhibited a unique proteomic profile with a modulated energy metabolism in PLWHEC compared to PLWHART independent of CCR6 status. The CD4+CCR6+ cells also showed an enrichment in proteins involved in apoptosis and p53 signalling in PLWHEC compared to PLWHART, indicative of increased sensitivity towards cell death mechanisms. Collectively, this data shows how PLWHEC have a unique chemokine receptor profile that may aid in facilitating natural control of HIV-1 infection.
© 2022. The Author(s).

HIV-1 elite controllers (EC) are a rare but heterogeneous group of HIV-1-infected individuals who can suppress viral replication in the absence of antiretroviral therapy. The mechanisms of how EC achieve undetectable viral loads remain unclear. This study aimed to investigate host plasma metabolomics and targeted plasma proteomics in a Swedish HIV-1 cohort including EC and treatment-naïve viremic progressors (VP) as well as HIV-negative individuals (HC) to get insights into EC phenotype. Metabolites belonging to antioxidant defense had higher levels in EC relative to VP, whereas inflammation markers were increased in VP compared with EC. Only four plasma proteins (CCL4, CCL7, CCL20, and NOS3) were increased in EC compared with HC, and CCL20/CCR6 axis can play an essential role in EC status. Our study suggests that low-level inflammation and oxidative stress at physiological levels could be important factors contributing to elite control phenotype.
© 2021 The Author(s).