Reconstructing the course of HIV-1-associated progressive encephalopathy in children.
The factors that trigger the clinical onset of HIV-1-associated progressive encephalopathy (PE) in children remain unknown. HIV-1 invades the central nervous system (CNS) from the very beginning of infection, but the timeframe for PE development is variable. It has recently been suggested that increased traffic into the brain of HIV-1-infected or activated monocytes arising directly from the bone marrow may be the first step to clinical onset of adult HIV encephalopathy. The determining factor for this enhanced recruitment of blood monocytes into the CNS in adults has been postulated to be increased HIV-1 replication. However, children usually exhibit high levels of viral load beginning in the first months of life, even under very aggressive antiretroviral therapy. PE in children represents a unique form of CNS involvement of HIV, much more common, early, and devastating for children than for adults, representing in fact an independent cause of mortality. In the light of recent literature on this issue and our own in vitro and in vivo results the possible mechanisms implicated in the pathogenesis of PE are discussed. We propose that CD8+ T-lymphocytes would be the nexus for all the various aspects of the disease, namely the loss of control over HIV-1 replication, increased traffic of activated monocytes, the spread of infection to immune sanctuaries and finally the neurological emergence of PE. Possible new biologic markers
Sánchez-Ramón
Silvia
S
Department of Immunology, Hospital General Universitario Gregorio Marañón, Madrid, Spain.
Cantó-Nogués
Carmen
C
Muñoz-Fernández
Angeles
A
D015526:AIDS Dementia Complex / Q000209:etiology* / Q000276:immunology / Q000503:physiopathology; D000328:Adult; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology / Q000378:metabolism; D002648:Child; D015658:HIV Infections / Q000276:immunology / Q000503:physiopathology*; D015497:HIV-1; D006801:Humans; D008954:Models, Biological; D014779:Virus Replication