Highly Active Antiretroviral Therapy Improves Neurocognitive
Highly Active Antiretroviral Therapy Improves Neurocognitive
Although the effects of highly active antiretroviral therapy (HAART) have resulted in substantial improvements in the systemic health of patients with HIV infection, concerns remain that these medications, which cross the blood-brain barrier poorly, may have a less beneficial effect on nervous system function. This raises the possibility that there may be a progressive long-term decline in neurologic function in patients with adequate systemic response. In a prospective longitudinal study, subjects were evaluated immediately before instituting HAART. Forty-eight subjects underwent ultrasensitive HIV RNA quantitative evaluation of both plasma and cerebrospinal fluid as well as neurologic and neuropsychological examinations. They were reevaluated 6 months after treatment initiation while receiving stable HAART. Both plasma and cerebrospinal fluid viral levels significantly declined after treatment. There was significant improvement in neurologic and neuropsychological functioning after HAART. These results indicate that despite the poor central nervous system penetration of most of these agents, there is satisfactory short-term improvement in both central nervous system viral burden and nervous system function with HAART. However, because treatment failure is increasingly likely over time, continued longitudinal evaluation of this group of subjects is required.
HIV is known to enter the central nervous system (CNS) within hours or days of initial infection and to remain sequestered in the brain. Many HIV-infected patients develop CNS and peripheral nervous system diseases. The most severe of these is AIDS dementia complex or HIV-associated dementia (HAD). When compared with matched control groups, patients may also have significant but less severe cognitive abnormalities demonstrated by detailed neuropsychological testing. This condition has been labeled minor cognitive motor dysfunction. Treatment with antiretroviral medication may result in improvement in dementia. There have been reports that highly active antiretroviral therapy (HAART) may lead to striking improvement in HAD in individual cases. Administration of HAART also appears to be associated with a decline in the incidence of dementia. However, there are reports of continued progression of HAD despite therapy. Further, with the prolongation in survival associated with more effective viral control, the prevalence of HAD does not appear to be decreasing. HAART results in only very low levels of drug in the CNS, and there is concern that HAART may afford effective systemic treatment but allow continued decline in nervous system function over time. A further concern is that HAART, with its known mitochondrial toxicity, may prove to be neurotoxic over time, leading to progression of nervous system dysfunction despite adequate viral control. To address these concerns, we are conducting a longitudinal evaluation of nervous system performance in a group of subjects before and after the institution of HAART. We report the results of baseline evaluation and 6-month follow-up of these subjects.
Although the effects of highly active antiretroviral therapy (HAART) have resulted in substantial improvements in the systemic health of patients with HIV infection, concerns remain that these medications, which cross the blood-brain barrier poorly, may have a less beneficial effect on nervous system function. This raises the possibility that there may be a progressive long-term decline in neurologic function in patients with adequate systemic response. In a prospective longitudinal study, subjects were evaluated immediately before instituting HAART. Forty-eight subjects underwent ultrasensitive HIV RNA quantitative evaluation of both plasma and cerebrospinal fluid as well as neurologic and neuropsychological examinations. They were reevaluated 6 months after treatment initiation while receiving stable HAART. Both plasma and cerebrospinal fluid viral levels significantly declined after treatment. There was significant improvement in neurologic and neuropsychological functioning after HAART. These results indicate that despite the poor central nervous system penetration of most of these agents, there is satisfactory short-term improvement in both central nervous system viral burden and nervous system function with HAART. However, because treatment failure is increasingly likely over time, continued longitudinal evaluation of this group of subjects is required.
HIV is known to enter the central nervous system (CNS) within hours or days of initial infection and to remain sequestered in the brain. Many HIV-infected patients develop CNS and peripheral nervous system diseases. The most severe of these is AIDS dementia complex or HIV-associated dementia (HAD). When compared with matched control groups, patients may also have significant but less severe cognitive abnormalities demonstrated by detailed neuropsychological testing. This condition has been labeled minor cognitive motor dysfunction. Treatment with antiretroviral medication may result in improvement in dementia. There have been reports that highly active antiretroviral therapy (HAART) may lead to striking improvement in HAD in individual cases. Administration of HAART also appears to be associated with a decline in the incidence of dementia. However, there are reports of continued progression of HAD despite therapy. Further, with the prolongation in survival associated with more effective viral control, the prevalence of HAD does not appear to be decreasing. HAART results in only very low levels of drug in the CNS, and there is concern that HAART may afford effective systemic treatment but allow continued decline in nervous system function over time. A further concern is that HAART, with its known mitochondrial toxicity, may prove to be neurotoxic over time, leading to progression of nervous system dysfunction despite adequate viral control. To address these concerns, we are conducting a longitudinal evaluation of nervous system performance in a group of subjects before and after the institution of HAART. We report the results of baseline evaluation and 6-month follow-up of these subjects.
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