Introduction
infection, ART-suppressed early-treated, neurological disorders
DISEASE PROGRESSION, VIRUS, HIV-1 INFECTION, INFECTION, NEUROLOGICAL DISORDERS
Since its identification in the 1980’s, the human immunodeficiency virus HIV type 1 (HIV-1) represents a major global public health issue. Although combination antiretroviral therapy (ART) effectively suppresses HIV-1 replication and slows disease progression, there is no effective cure for HIV-1 infection. Moreover, ART is associated with viral resistance and treatment-related side effects and, even more importantly, is not accessible worldwide, reinforcing the urgent need for a HIV cure. During the last decade, different cure strategies have been explored, some of them based on latency reactivators, such as histone deacetylase inhibitors, which make host-cell chromatin more accessible to transcription factors. However their use can also impact host gene expression,BCN02 was a single-arm, open-label clinical trial (NCT02616874) that enrolled 15 ART-suppressed early-treated, HIV-1+ individuals to receive a combination of 3 series of the LRA RMD and MVA.HIVconsv vaccines.Although the BCN02 clinical trial included early treated individuals who initiated ART less than 6 months after infection and who therefore may present with smaller and less-diverse viral reservoirs, the virus systematically rebounds from this reservoir and is the major challenge for cure strategies. While the contribution of different anatomical compartments of the viral reservoirs to rebound remains unclear, it is known that after acquisition, HIV-1 also infects the central nervous system (CNS) and represents one of the anatomical compartments for latently infected cells.To further explore the impact of the therapeutic vaccination and LRA RMD on plasma markers of virus control and CNS integrity, longitudinally plasma proteome profiling was conducted in the BCN02 study samples. Overall, RMD administration and ART interruption strongly increased the protein levels of host factors involved in inflammatory processes but also that of markers of neurological disorders that all correlated with clinical, viral, as well as cognitive parameters. These longitudinal inflammatory/neurological profiles uniquely identified CD33/sialic-acid-binding immunoglobulin-like lectin 3 (Siglec-3), whose elevated plasma levels were associated with MAP non-control. Higher CD33/Siglec-3 plasma levels were also observed in individuals with high viral loads in an unrelated cohort with untreated HIV-1 infection. The clinical relevance of these findings is further supported by our observation that anti-CD33 monoclonal antibody 