Neurodevelopmental/Neuroradiologic Recovery of a Child Infected With HIV After Treatment With Combination Antiretroviral Therapy Using the HIV-Specific Protease Inhibitor Ritonavir

Abstract

An 8-year, 2-month-old African-American boy was infected with HIV through vertical transmission. Regular monitoring of the patient's neurodevelopmental status has been conducted as part of his participation in longitudinal research protocols. For the first 51/2 years of life, his neurodevelopmental status was normal, with cognitive functioning as measured by standardized psychometric tools solidly in the average range. Speech and language skills were age-appropriate. Tests of gross and fine motor functioning as well as evaluation of overall neurodevelopmental status suggested normal development. Magnetic resonance imaging (MRI) of the brain was consistently normal. His family reported that adaptive functioning, peer and family relationships, and behavior were all within normal limits. School reports indicated consistently that the patient was performing at age and grade level, with respect to both academic achievement and behavior. Initial concerns regarding the patient's development were expressed by both his family and school at age 6 years, 6 months. These concerns included difficulty with classroom work, decreased attention, word-finding problems, fatigue, staring spells, and loss of strength. His family and school reported a marked loss of skills acquired previously. Results of formal psychological and speech and language evaluation reflected statistically significant drops in test scores from baseline, with both delayed and atypical skills evident. The patient's condition worsened rapidly. Within a few months, he was no longer able to use sentences to communicate. Cognitive testing was attempted, but he was unable to participate because of significant fatigue, limited attention, and inability to communicate verbally. His family described periods of disorientation and confusion, lethargy, and disinterest in age-appropriate activities. He became agitated and overstimulated easily both in small group settings and in crowds. He demonstrated both fine and gross motor impairments. When frustrated, he displayed infantile and autistic-like behavior. MRI with contrast showed diffuse atrophy as well as mild prominence of the ventricles and sulcii compared with baseline assessment. In addition to fatigue and neurologic symptoms, wasting syndrome was diagnosed, with loss of percentiles in both weight and height by age 71/2 years. Low-grade elevation of liver function tests and amylase was noted. Blood cultures for mycobacteria were negative, as were serologic tests for hepatitis. (ABSTRACT TRUN

Protecting the Synapse: Evidence for a Rational Strategy to Treat HIV-1 Associated Neurologic Disease

“…After 12 weeks of antiretroviral therapy that decreased viral burden and associated inflammatory markers in the plasma and cerebrospinal fluid (CSF), her performance on cognitive and motor testing had dramatically improved and most but not all of her presenting deficits were reversed. Similar clinical recovery, accompanied by reversal of radiologic signs of cerebral atrophy, was reported after antiretroviral therapy in an HIV-1-infected child with language, attention, and motor deficits that had caused him to lose developmental milestones and prevented him from communicating with others at school and at home (Tepper et al 1998). Cohort studies following patients beginning highly active antiretroviral therapy (HAART) provide further evidence of a large reversible component in HAD (Thurnher et al 2000;Ferrando et al 2003).…”

Incidence and prevalence of HIV encephalopathy in children with HIV infection receiving highly active anti-retroviral therapy (HAART)

“…9 In addition, McCoig et al observed that children infected with HIV who were on combination anti-retroviral therapies showed a significant decline in neurologic abnormalities, as well as viral load (VL), throughout the course of treatment. 10 Nevertheless, the incidence of PHE and the clinical manifestations of PHE have not been systematically assessed since the introduction of HAART.…”

Glycogen Synthase Kinase 3 Beta (GSK-3β) as a Therapeutic Target in NeuroAIDS

“…This supposition is based on neuropathologic data obtained from patients in the pre-HAART era, but is buttressed by reports of adult and pediatric patients with HIV-1 and neurologic disease that experienced substantial improvement in both neuropsychologic and neuroradiologic indices (Gendelman et al 1998;Tepper et al 1998). Further support for antiviral amelioration of neurologic disease associated with lentiviral infection can be garnered from studies by Fox et al (2000) using SIV-infected rhesus macaques, where the authors have demonstrated that treatment with PMPA ameliorates neuropsychological deficits and normalizes sensory-evoked potentials (SEPs), a measure of the integrity of brainstem polysynaptic pathways in response to an event-related stimulus (such as light, sound, or recognition of a singular event in a stimulation pattern), but does not reverse motor deficits.…”