HIV-1 encephalopathy among perinatally infected children: Neuropathogenesis and response to highly active antiretroviral therapy.
HIV-1 encephalopathy among perinatally infected children in the United States was initially defined by a classic triad of findings that included: (1) developmental delay, (2) secondary or acquired microcephaly, and (3) pyramidal tract neuromotor deficits. The most severe form of this disorder typically occurred among young children who developed rapidly progressive disease in concert with profound immunosuppression, and Pneumocystis jiroveci pneumonitis (PCP). The neuropathogenesis of this disorder appears to involve a cascade of viral products, various cytokines and chemokines, and neurotransmitters which promote ongoing inflammation, excitation, and overstimualtion of the N-methyl-D-aspartate type receptor (NMDAR) system. These subsequently lead to neuronal injury and death secondary to apoptosis or necrosis, astrocytosis, as well as dentritic and synaptic damage. The frequency of the most severe forms of encephalopathy among children has dropped dramatically since the introduction of highly active antiretroviral therapy (HAART). Of concern, however, is the possibility that a more insidious form of this disorder may be occurring presently among older vertically infected children as a result of inadequate penetration of HAART agents into the cerebrospinal fluid (CSF). This paper will review what published data there is as yet that bears on this question.
Mitchell
Charles D
CD
Department of Pediatrics, Leonard M. Miller School of Medicine, University of Miami, Miami, Florida, USA.
D015526:AIDS Dementia Complex / Q000175:diagnosis* / Q000188:drug therapy; D000328:Adult; D023241:Antiretroviral Therapy, Highly Active / Q000009:adverse effects; D001921:Brain / Q000187:drug effects / Q000473:pathology; D002648:Child; D002675:Child, Preschool; D002658:Developmental Disabilities / Q000175:diagnosis* / Q000209:etiology; D015658:HIV Infections / Q000151:congenital* / Q000188:drug therapy; D015497:HIV-1 / Q000187:drug effects; D006801:Humans; D007223:Infant; D007231:Infant, Newborn; D018445:Infectious Disease Transmission, Vertical / Q000517:prevention & control; D008607:Intellectual Disability / Q000175:diagnosis* / Q000209:etiology; D011379:Prognosis; D012307:Risk Factors; D016896:Treatment Outcome; D019562:Viral Load