HIV suppression by HAART preserves cognitive function in advanced, immune-reconstituted AIDS patients. AIDS

Harvard University, Cambridge, Massachusetts, United States
AIDS (Impact Factor: 5.55). 05/2007; 21(9):1109-17. DOI: 10.1097/QAD.0b013e3280ef6acd
Source: PubMed


HIV can damage neurons leading to cognitive impairment. Epidemiological observations suggest that neuropsychological impairment might progress despite successful HAART therapy, but available prevalence estimates are based on populations that were selected for impairment.
Of 433 advanced AIDS patients with documented immune reconstitution (CD4 lymphocyte counts < 50 before and > 100 cells/microl after HAART), 286 had brief assessments of cognition (Trailmaking A/B and Digit Symbol Tests) at least once, no confounding neurological conditions, and available neuropsychological norms with comprehensive demographic corrections. At entry, most were immune reconstituted on HAART (median CD4 cell count 230 cells/microl) and HIV was suppressed (65% < 500; only 14% > 20 000 RNA copies/ml).
Over one quarter (27%) of participants exhibited impairment at their initial neuropsychological assessment, a rate nearly twice that expected in a normal (HIV-uninfected) reference population (14%). These impaired participants did not differ from the unimpaired group with respect to age, sex, education, race, CD4 lymphocyte counts, or HIV-RNA levels. Improved performance on neuropsychological tests was documented over a 2-year period 3-5 years after initiating HAART. This improvement was marginally associated with the continued or improving control of plasma HIV-RNA levels, but not with concurrent levels of immune recovery (CD4 lymphocyte counts).
Most advanced AIDS patients responding to HAART for prolonged periods have stable or improving cognition, but remain more likely to be impaired than the general population. During HAART, improving test performance probably reflects both practice effects and continuing neurological recovery after more than 3 years of HAART.

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    • "O principal objetivo da TARV seria, através da inibição da replicação viral, retardar o progresso da imunodeficiência e restaurar, tanto quanto possível, a imunidade, contribuindo para o aumento da sobrevida das pessoas. Assim, no que se refere aos aspectos clínicos, verifica-se que o uso combinado de três ou mais drogas antirretrovirais prolonga a sobrevida das pessoas e pode também reduzir a incidência de transtornos psicológicos associados ao HIV (McCutchan et al., 2007), estando tal redução estritamente relacionada com o tempo decorrido para o início do tratamento e a adesão ao mesmo no decorrer do processo. "
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    ABSTRACT: O advento da terapia antirretroviral trouxe a necessidade de se compreender os determinantes psicossociais envolvidos na avaliação de qualidade de vida em pessoas que vivem com HIV/AIDS. O objetivo desse estudo é investigar os determinantes psicossociais e clínicos envolvidos na avaliação de qualidade de vida nesse grupo social. Esta pesquisa envolveu 90 pessoas vivendo com HIV/AIDS (média de idade de 33,7 anos, DP = 6,6). Um questionário sócio-demográfico e clínico e o WHOQOL-BREF constituíram os principais métodos. Análises descritivas, comparações entre médias de grupos-critério e análise de regressão foram utilizadas. Os resultados demonstram melhor qualidade de vida entre os que estavam satisfeitos com os serviços de saúde do hospital, bem como os principais determinantes para a avaliação de qualidade de vida são a dimensão psicológica, contagens de células CD4 e a dimensão ambiental. Essa pesquisa sugere a elaboração de políticas públicas de saúde em HIV/AIDS que englobem os fatores psicossociais.
    Full-text · Article · Dec 2013 · Estudos de Psicologia (Natal)
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    • "With the introduction of highly active antiretroviral therapy (HAART), the morbility and mortality in HIV positive patients have been significantly reduced. Although HAART has lessen the incidence of HIV-associated dementia (HAD; McCutchan et al. 2007; Nath 2010), HIV positive patients continue to suffer from HIV-associated neurocognitive disorders (HAND) and the prevalence of HAD actually increased due to the extended lifespan in HIV positive patients and the resistance to HAART in some patients (Antinori et al. 2007; Gonzalez-Scarano and Martin-Garcia 2005; McArthur et al. 2003; Nath 2010). In addition, recent studies suggest that the greater incidence of drug abuse among HIV-positive patients may exacerbate the progression of HAD as the psychoactive drugs and the products of the HIV-1 virus interact additively or synergistically on common brain regions. "
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    ABSTRACT: The HIV-1 transgenic (HIV-1Tg) rat shows a deficit in learning to locate a submerged platform in a multiple-trial water maze task compared to transgenic littermate and F344 control rats (Vigorito et al., J.Neuroimmune Pharmacol 2:319-328, 2007; Lashomb et al., J.Neurovirol 15:14-24, 2009). Nicotine is known to have neuroprotective effects possibly by minimizing cytotoxic effects of glutamate or by modulating a cholinergic anti-inflammatory pathway. Nicotine also improves performance in a variety of learning tasks by enhancing attention and short-term memory (STM). The purpose of this study was to determine if the learning deficit in HIV-1Tg is ameliorated by repeated nicotine treatment independent of its effects on STM. HIV-1Tg and F344 rats were treated (subcutaneous) with nicotine (0.25 mg/kg/injection) or saline twice daily and tested in a single-trial-per-day procedure which precludes the impact of STM on the acquisition of the spatial learning task. HIV-1Tg rats showed a deficit in the acquisition of the task and in the long-term retention for the platform location in a probe test. Nicotine did not ameliorate the deficit in HIV-1Tg rats and slightly worsened performance during acquisition. Analysis of individual differences in performance during the probe test suggested that nicotine improved performance in some F344 rats but not in HIV-1Tg rats. These results indicate that a deficit in the consolidation of long-term memory contributes to the acquisition deficit of HIV1-Tg rats. The results, however, do not provide any evidence of the amelioration of the learning deficit observed in this behavioral model at least with the nicotine dose tested.
    Full-text · Article · Mar 2013 · Journal of NeuroVirology
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    • "Secondly, cognitive decline in HAND may result as much from neuronal dysfunction as from neuronal loss, an idea supported by experimental results showing alterations in cell layer volume [57] and dendritic morphology [4] correlate with HAD [58]. Indeed, extensive cell death is not always present when symptoms manifest [59] and antiretroviral therapy (ART) treatment has been known to lead to cognitive improvement [60], [61], [62], [63], suggesting the underlying pathology of HAD may be in part reversible. This is consistent with a channelopathy hypothesis originally described by Dr. Ben Gelman [64], which led our laboratory to investigate Kv channel involvement in HAND [65]. "
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