Neurodevelopmental/neuroradiologic recovery of a child infected with HIV after treatment with combination antiretroviral therapy using the HIV-specific protease inhibitor ritonavir

Abstract

Background: Neurodevelopmental impairment has been identified in children infected with human immunodeficiency virus (HIV). The frequency and spectrum of neurologic impairment are greater in children than those reported for adults. In children, HIV is known to enter the central nervous system early in the course of the disease. The presentation of pediatric neuro-acquired immune deficiency syndrome ranges from static (eg, nonprogressive developmental delay) to progressive encephalopathy (eg, acquired microcephaly, pyramidal tract signs, and spasticity). It has been demonstrated that antiretroviral agents can improve or even reverse the course of neurologic impairment in children. These changes have been attributed to various degrees of central nervous system drug penetration. Increasingly, protease inhibitors and combination antiretroviral therapy using reverse transcriptase inhibitors are being used in the treatment of children infected with HIV. The addition of a protease inhibitor to nucleoside analogue therapy has been reported to delay disease progression and prolong life in adults with moderate to advanced HIV disease. No data currently exist on the impact of combination therapy using two nucleoside analogues and a protease inhibitor on neurodevelopmental and neurologic function in children with HIV infection. The following case report presents the effects of combination therapy using ritonavir in a child infected with HIV.

Case report: 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