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One Third With Undetectable HIV RNA Have
Asymptomatic Neurocognitive Impairment
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5th IAS Conference on HIV Pathogenesis, Treatment and Prevention, July 19-22, 2009, Cape Town
Mark Mascolini
One third of 45 people taking suppressive antiretroviral therapy had asymptomatic neurocognitive impairment on a 40-minute computerized test [1]. Surprisingly, younger people studied in this the British HIV clinic appeared to have worse impairment, but the small size of this study indicates a need for caution in interpreting results.
Numerous studies show that neurocognitive impairment remains prevalent in people taking potent antiretroviral combinations and that this impairment can affect the ability to perform routine daily activities, get a job, or adhere to antiretroviral therapy. HIV-associated neurocognitive deficits include HIV-associated dementia, symptomatic neurocognitive impairment (which affects daily activities), and asymptomatic impairment (which can be diagnosed only by neurocognitive assessment).
Because little work has addressed asymptomatic impairment in people with an undetectable viral load in plasma, researchers at the University College London tested 45 people in April and May 2008 with CogState, a computerized test that has a high positive predictive value for detecting HIV-associated neurocognitive impairment. The test measures psychomotor function, visual attention, executive function, memory, and learning and compares results with an age-matched general-population sample. For this study, the investigators defined asymptomatic neurocognitive impairment as performance more than 1 standard deviation below the age-stratified normative average in at least two cognitive domains on the test.
Study participants had to be taking a stable antiretroviral regimen that kept plasma viremia below 50 copies for at least 3 months. They could not have active neurologic disease, dementia, or hepatitis C virus infection, and they could not use recreational drugs or drink excessive alcohol.
The study group averaged 45 years in age (standard deviation [SD] 11), 546 CD4 cells (SD 271), and 12.2 years since HIV diagnosis (SD 6). Twenty-three people (51%) were taking their first combination, 17 (38%) their second, and 5 (11%) their third or later. The average central nervous system penetration score of their regimens was 1.76 (SD 0.68), which indicates moderate penetration. A score of 2 has been proposed as a marker of good penetration. Whether penetration score accurately predicts neurocognitive performance has yet to be established [2]. The investigators did not report potentially relevant demographics such as income, education, or race.
Fourteen of 45 study participants (31%) had asymptomatic neurocognitive impairment, which affected about half of 24-to-39-year-olds studied but lower proportions of 40-to-49-year-olds, 50-to-56-year-olds, and 57-to-67-year-olds. This correlation with younger age reached statistical significance (r = 0.32, P = 0.03). In contrast, current or lowest-ever CD4 count, time since HIV diagnosis, and nonnucleoside versus protease inhibitor treatment were not associated with neurocognitive impairment.
The investigators speculated that the higher neurocognitive impairment rate in younger adults could reflect their increased susceptibility to HIV's effects on the brain or differing educational and socioeconomic status in the study group and the healthy population used for comparison. The researchers suggested "clinicians should be aware of mild neuropsychological deficits when evaluating HIV-infected [people], regardless of disease stage."
References
1. Garvey L, Yerrakalva D, Winston A. High rates of asymptomatic neurocognitive impairment (aNCI) in HIV-1 infected subjects receiving stable combination anti-retroviral therapy (CART) with undetectable plasma HIV RNA. 5th IAS Conference on HIV Pathogenesis, Treatment and Prevention. July 19-22, 2009. Cape Town. Abstract MOPEB027.
2. Marra CM, Zhao Y, Clifford DB, et al. Impact of combination antiretroviral therapy on cerebrospinal fluid HIV RNA and neurocognitive performance. AIDS. 2009;23:1359-1366.
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