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Nadir CD4 Cell Count Predicts Neurocognitive Impairment in HIV-Infected Patients

Authors:
  • Fight Infections Foundation - Germans Trias i Pujol University Hospital

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Though antiretroviral therapy attenuates neurocognitive disruption, impairment is still observed. We studied the nadir CD4 cell count as a predictor of neurocognitive changes. This cross-sectional study assessed 64 HIV-infected patients in two groups: G1 (n = 26, nadir CD4 < or =200 cells/ml) and G2 (n = 38, nadir CD4 >200 cells/ml). Percentages of patients showing neurocognitive impairment were compared according to different nadir CD4 cutoffs (200, 250, 300, and 350 cells/ml). From G2, we also took the subgroup of patients receiving treatment (G3) and compared this group with G1, in which all patients were being treated. Demographic and clinical variables were evaluated, as were differences in neurocognitive function. Neurocognitive impairment tended to be more prevalent in G1 [19 patients (73.1%)] than in G2 [20 (52.6%), p = 0.123]. When nadir CD4 cutoffs were compared, there was a trend toward more impaired subjects as the CD4 nadir decreased. Significantly different functioning was found in attention/working memory (digit span backward, p = 0.032) and executive functions (trail making test, part B, p = 0.020), with better performance in G2. Comparison between G1 and G3 confirmed those findings. We found differences in neurocognitive functioning in relation to nadir CD4 count in HIV-infected patients. Attention should be given to this value in the management of neurocognitive protection in HIV infection.
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... METH is also associated with delayed HIV diagnosis and antiretroviral therapy initiation (Kuchinad et al., 2016;Passaro et al., 2015), leading to early and more severe immunosuppression, potentially driving irreversible injury to frontal brain systems, resulting in enduring cognitive impairments that persist despite subsequent VLS (Heaton et al., 2010Muñoz-Moreno et al., 2008). Thus, HIV +/METH persons may be at greatest risk of cognitive impairment. ...
... This discrepancy in findings may be attributable to the high nadir CD4 counts among PWH in the current study, reflecting on average, the absence of previous immunosuppression. Alternatively, these results may indicate that while untreated HIV has an irreversible, detrimental impact on psychomotor and some cognitive functions (Muñoz-Moreno et al., 2008), sustained attention and vigilance may be spared from enduring deficits. Results may also indicate that while antiretroviral therapy has pro-cognitive effects for some domains, it has little effect on psychomotor function. ...
Article
Background Human immunodeficiency virus (HIV)-associated neurocognitive disorders persist in the era of antiretroviral therapy. One factor that is elevated among persons with HIV (PWH) and independently associated with neurocognitive impairment is methamphetamine dependence (METH). Such dependence may further increase cognitive impairment among PWH, by delaying HIV diagnosis (and thus, antiretroviral therapy initiation), which has been posited to account for persistent cognitive impairment among PWH, despite subsequent treatment-related viral load suppression (VLS; <50 copies of the virus per milliliter in plasma or cerebrospinal fluid). This study examined the independent and combined (additive versus synergistic) effects of HIV and history of METH on the sustained attention and vigilance cognitive domain, while controlling for VLS. Methods Participants included 205 (median age = 44 years; 77% males; HIV-/METH- n = 67; HIV+/METH - n = 49; HIV-/METH+ n = 36; HIV+/METH+ n = 53) individuals enrolled in the Translational Methamphetamine AIDS Research Center, who completed Conners’ and the 5-Choice continuous performance tests (CPTs). Results METH participants exhibited deficits in sustained attention and vigilance; however, these effects were not significant after excluding participants who had a positive urine toxicology screen for methamphetamine. Controlling for VLS, PWH did not have worse sustained attention and vigilance, but consistently displayed slower reaction times across blocks, relative to HIV- participants. There was no HIV x METH interaction on sustained attention and vigilance. Conclusions Recent methamphetamine use among METH people and detectable viral loads are detrimental to sustained attention and vigilance. These findings highlight the need for prompt diagnosis of HIV and initiation of antiretroviral therapy, and METH use interventions.
... Briefly, CD4+ T cells are prominent indicators of immune system stability in PLWH, as their levels dramatically decrease immediately upon infection (Leung et al., 2013;Serrano-Villar et al., 2014). Further, lower CD4 nadir values (i.e., lowest lifetime cell count) have been directly implicated in both the relative age advancement (e.g., DNA methylation) and the likelihood of cognitive impairment in PLWH (Tozzi et al., 2005;Muñoz-Moreno et al., 2008;Ellis et al., 2011;Gross et al., 2016). Thus, we expected our neural markers of somatosensory function to be closely tied to these important clinical measures in PLWH. ...
... Importantly, this increase was not only modulated by HIV-infection, but was specifically related to CD4 nadir across all PLWH. With increasing evidence suggesting that CD4 nadir is predictive of cognitive impairment in these participants (Tozzi et al., 2005;Muñoz-Moreno et al., 2008;Ellis et al., 2011;Services, 2017), the need for early diagnosis and treatment initiation is clear and of utmost importance. ...
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... We speculate that these relations may be due to cognitive reserve (Richards & Deary, 2005) in individuals with higher education and SES levels and stresses a potential role of resources and their availability in mitigating impairment (Chang, Holt, Yakupov, Jiang, & Ernst, 2013;Marin-Webb, Jessen, Kopp, Jessen, & Hahn, 2016). Earlier studies reported that an AIDS diagnosis and a low nadir CD4 were predictors of neurocognitive impairment (Ellis et al., 2011;Munoz-Moreno et al., 2008); however, neither an AIDS diagnosis nor nadir CD4 cell count accounted for lower cognitive scores in any of the domains assessed in our cohort of older adults with HIV infection who were adherent on ART and had current CD4 + T-cell counts in the normal range. A possible explanation is that HAART has considerably altered the disease course such that the pathogenic virus-brain interaction is less direct (Eggers et al., 2017) and the association between past HIV-related CNS injury and later neurocognitive impairment is less common. ...
Article
Despite the life-extending success of antiretroviral pharmacotherapy in HIV infection (HIV), the prevalence of mild cognitive impairment in HIV remains high. Near-normal life expectancy invokes an emerging role for age-infection interaction and a potential synergy between immunosenescence and HIV-related health factors, increasing risk of cognitive and motor impairment associated with degradation in corticostriatal circuits. These neural systems are also compromised in Parkinson's disease (PD), which could help model the cognitive deficit pattern in HIV. This cross-sectional study examined three groups, age 45-79 years: 42 HIV, 41 PD, and 37 control (CTRL) participants, tested at Stanford University Medical School and SRI International. Neuropsychological tests assessed executive function (EF), information processing speed (IPS), episodic memory (MEM), visuospatial processing (VSP), and upper motor (MOT) speed and dexterity. The HIV and PD deficit profiles were similar for EF, MEM, and VSP. Although only the PD group was impaired on MOT compared with CTRL, MOT scores were related to cognitive scores in HIV but not PD. Performance was not related to depressive symptoms, socioeconomic status, or CD4+ T-cell counts. The overlap of HIV-PD cognitive deficits implicates frontostriatal disruption in both conditions. The motor-cognitive score relation in HIV provides further support for the hypothesis that these processes share similar underlying mechanisms in HIV infection possibly expressed with or exacerbated by ageing.
... It is increased subsequently about HIV contagion, which is determined by the CD4 T-cell count and plasma viral load. Many times, these characteristics appear as the first symptoms of initiation of AIDS [20,54]. ...
Chapter
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The catastrophic rise in numeral of individuals suffered from human immunodeficiency virus (HIV)/Acquired immunodeficiency syndrome (AIDS) has necessitated global concern for finding an effective solution to prevent HIV infection. Though the combination antiretroviral therapy (cART) is effective in regards to prevention of HIV proliferation, which doesn’t deprive of from adverse consequences, which multiply over the life long treatment. Moreover, the emergence of drug resistance limits the cART, and hence novel drugs as well as newer objects are the necessity of the epoch have to worked upon. In this pursuance, the research for the drugs that attack HIV reservoirs, like brain, lymph nodes, blood, and digestive tract, has shifted our focus towards plant metabolites, like coumarins, terpenes, flavonoids, alkaloids, phenolics, lignans, quinones, saponins, etc. These metabolites have shown promising anti-HIV and neuroprotective properties. The present chapter focuses on biodiversity of flora monarchy as well as presents an overview of the potential of such plant extracts against HIV/AIDS along with their function in relation of HIV-associated neurocognitive disorders (HAND).
... Studies of diverse populations of PLWH in different settings showed that higher nadir CD4 counts were associated with reduced likelihood of HAND, whereas low nadir CD4 counts predicted cerebral atrophy 78 and neurocognitive impairment [79][80][81][82][83][84] . In the current ART era there have been conflicting evidence as to whether there is a link between current immunosuppression and risk of neurocognitive impairment. ...
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Background Human immunodeficiency virus (HIV)-associated neurocognitive disorders persist in the era of antiretroviral therapy (ART). One factor that is elevated among persons with HIV (PWH) and independently associated with neurocognitive impairment is methamphetamine dependence (METH+). Such dependence may further increase cognitive impairment among PWH, by delaying HIV diagnosis (and thus, ART initiation), which has been posited to account for persistent cognitive impairment among PWH, despite subsequent treatment-related viral load suppression (VLS; ≤50 copies of the virus per milliliter in plasma or cerebrospinal fluid). This study examined the independent and combined (additive versus synergistic) effects of HIV and history of METH+ on the sustained attention and vigilance cognitive domain, while controlling for VLS. Methods Participants included 205 (median age=44 years; 77% males; HIV-/METH- n =67; HIV+/METH - n =49; HIV-/METH+ n =36; HIV+/METH+ n =53) individuals enrolled in the Translational Methamphetamine AIDS Research Center, who completed Conners’ and the 5- Choice continuous performance tests (CPTs). Results METH+ participants exhibited deficits in sustained attention and vigilance; however, these effects were not significant after excluding participants who had a positive urine toxicology screen for methamphetamine. Controlling for VLS, PWH did not have worse sustained attention and vigilance, but consistently displayed slower reaction times across blocks, relative to HIV-participants. There was no HIV x METH interaction on sustained attention and vigilance. Conclusions Recent methamphetamine use among METH+ people and detectable viral loads are detrimental to sustained attention and vigilance. These findings highlight the need for prompt diagnosis of HIV and initiation of ART, and METH use interventions.
Article
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This study aimed to determine the prevalence and determinants of HIV-associated neurocognitive disorder (HAND) and its subgroups in HIV-positive patients in Tehran, Iran. Ninety-three HIV-positive individuals were assessed; the majority were male (60%) and the mean age of patients was 36.5 years (SD = 9), with 8 years as the median duration of HIV infection. The relationship between demographic and clinical variables was examined using logistic regression analysis. The overall prevalences of HAND and cognitive complaints were 50.5% and 73%, respectively. Lower nadir CD4 counts ( 200), lower educational levels (  12 years), longer disease duration ( ≥ 5years), and higher depression rates were positively associated with the presence of HAND. This study shows that the prevalence of HANDs in Iran is high, but similar to the prevalence levels found in Western societies. Further studies are needed to longitudinally evaluate the presence of HAND, in particularly to recognize new biomarkers and specific neurocognitive domains in HIV.
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Context Guidelines for antiretroviral therapy are important for clinicians worldwide given the complexity of the field and the varied clinical situations in which these agents are used. The International AIDS Society–USA panel has updated its recommendations as warranted by new developments in the field.Objective To provide physicians and other human immunodeficiency virus (HIV) clinicians with current recommendations for the use of antiretroviral therapy in HIV-infected adults in circumstances for which there is relatively unrestricted access to drugs and monitoring tools. The recommendations are centered on 4 key issues: when to start antiretroviral therapy; what to start; when to change; and what to change. Antiretroviral therapy in special circumstances is also described.Data Sources and Study Selection A 16-member noncompensated panel was appointed, based on expertise in HIV research and patient care internationally. Data published or presented at selected scientific conferences from mid 2004 through May 2006 were identified and reviewed by all members of the panel.Data Extraction and Synthesis Data that might change previous guidelines were identified and reviewed. New guidelines were drafted by a writing committee and reviewed by the entire panel.Conclusions Antiretroviral therapy in adults continues to evolve rapidly, making delivery of state-of-the-art care challenging. Initiation of therapy continues to be recommended in all symptomatic persons and in asymptomatic persons after the CD4 cell count falls below 350/μL and before it declines to 200/μL. A nonnucleoside reverse transcriptase inhibitor or a protease inhibitor boosted with low-dose ritonavir each combined with 2 nucleoside (or nucleotide) reverse transcriptase inhibitors is recommended with choice being based on the individual patient profile. Therapy should be changed when toxicity or intolerance mandate it or when treatment failure is documented. The virologic target for patients with treatment failure is now a plasma HIV-1 RNA level below 50 copies/mL. Adherence to antiretroviral therapy in the short-term and the long-term is crucial for treatment success and must be continually reinforced.
Chapter
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Neurocognitive and motor functioning may be progressively affected in HIV-infected patients. This disruption starts with impairment on neuropsychological performance, usually with subtle changes, but it may also lead to important neurocognitive complications. The current anti-HIV treatments may improve these neuropsychological disorders, although a total recovery is not completely achieved. In addition, in clinical practice, people living with HIV frequently report problems with their cognitive functioning in their routine clinical visits, pointing attention and memory as the main functions affected. Though many different studies assessing neurocognitive impairment in HIV infection have been published, an standard approach to optimally assess neuropsychological deficits does not currently exist. Moreover, when HIV-infected patients present a good immunological status, neuropsychological changes are usually subtle and affect few neurocognitive domains. For these reasons, it is necessary a rigorous and adequate assessment of impaired neurocognitive functioning. Until now, few strategies have been recommended for the improvement of cognitive disorders in patients with HIV infection. This chapter describes the most common neurocognitive and motor disorders associated with HIV infection, provides a summarized approach for an adequate assessment of these manifestations, and discusses possible clinical interventions focused on the preservation of neuropsychological functioning in the HIV infected population.