Abstract

While HIV encephalopathy and the AIDS dementia complex are considered hallmark neurologic manifestations of HIV-1 infection, increasing evidence of a continuum of nervous system involvement indicates the existence of an unrecognized number of individuals with milder, mostly cognitive and/or behavioural effects. Questions are raised whether HIV-related frontotemporal neuropathology during critical developmental stages could affect development of the brain networks documented to be involved in moral decisions, and whether this could contribute to the phenomenon of delinquency in an unknown percentage of the current generation of approximately 18-25 year old survivors of early childhood or vertically acquired HIV infection. Carefully planned and executed long term, prospective controlled studies using environmental, clinical, neurological, behavioural, genetic, immune and functional neuroimaging correlates would be required to elucidate whether HIV-specific neuropathology could indeed act as an independent risk factor for the development of a frontotemporal sociopathy syndrome. If such an association is proven, the accelerated development of neurospecific therapies should be a priority, especially for clinically and immunologically stable HIV-infected children. It may be necessary to institute such treatment as early as possible in perinatally infected cases, and maybe even during intrauterine life if HIV-1 is demonstrated to also act as a neurobehavioural teratogen for the developing fetal brain. It may, however, prove to be difficult to separate primary neurobiological from environmental factors, since the epigenetic effects on the host genome of retroviral insertion influencing behavioural gene expression characteristics, and altered gene expression following early life stresses may involve overlapping neurodevelopmental gene regulatory networks. In the meantime it remains necessary to prevent or ameliorate frequent neuropsychiatric morbidity from whatever causes.

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