Cognitive and motor deficits associated with HIV-2(287) infection in infant pigtailed macaques: a nonhuman primate model of pediatric neuro-AIDS

Abstract

Lentivirus-infected nonhuman primates exhibit behavioral and neurological pathology similar to human immunodeficiency virus (HIV)-infected humans and offer a means to examine the effects of lentivirus infection while controlling for confounding factors inherent in human populations. The purpose of this study was to examine cognitive and motor development in infant macaques vertically infected with HIV-2287. Subjects were 20 infant pigtail macaques (Macaca nemestrina); 8 controls born to uninfected dams, and 12 infants whose dams had been inoculated and infected with HIV-2287 in the third trimester of pregnancy. Eight of these pregnancies had undergone surgical procedures in the form of maternal amniotic catheters or maternal amniotic and fetal carotid artery and jugular vein catheters. Data indicated that catheterization had little or no impact on behavioral development. Seven infants were vertically infected (as measured by polymerase chain reaction (PCR) at birth) and five were not infected (as measured by PCR and coculture on repeated testing). Infected infants attained cognitive and motor milestones at significantly later ages than controls. Uninfected infants, born to infected dams, attained developmental milestones at later ages than controls on all tasks, but this reached statistical significance only for the Fine Motor Task. Attainment of milestones was not correlated with viral dose, maternal CD4+ levels at parturition or infant viral RNA levels at birth. Attainment of milestones was negatively correlated with infants' proportions of CD4+ lymphocytes at birth and significantly correlated with proportions of CD4+ lymphocytes 2 weeks after birth, indicating poorer performance in those infants with a more rapid CD4+ depletion. These cognitive and motor deficits closely resemble those observed in human infants and children infected with HIV and indicate that HIV-2287-infected infant macaques represent an excellent model of pediatric neuro-acquired immunodeficiency syndrome (neuroAIDS).