Kaitlin Blackstone

Defining Neurocognitive Impairment in HIV: Deficit Scores Versus Clinical Ratings

Because HIV-related neurocognitive impairment is usually mild and variable, clinical ratings (CR) and global deficit scores (GDS) are recommended for detecting HIV-associated neurocognitive disorders (HAND). The CR approach requires impairment in at least two ability domains while the GDS considers number and severity of impairments across all measures. We examined classification agreement and clinical correlates of the two methods. Neurocognitive functioning of 1574 HIV-infected participants was assessed via a comprehensive, seven-domain neuropsychological battery. Global neurocognitive impairment was defined for each participant independently by CR and GDS. Participants were classified into four categories (Dually-normal, [impaired by] CR-only, [impaired by] GDS-only, or Dually-impaired). There was 83% concordance between CR and GDS classifications; in total, 56% of participants were deemed impaired by CR and 41% were classified as impaired by GDS. Impairment by GDS virtually guaranteed CR impairment, but 16% of participants were additionally classified as impaired only by CR. As compared to Dually-normal participants, those classified as Dually and CR-only impaired were more likely to have AIDS, have more severe co-occurring conditions, have more severe depressive symptoms, be unemployed, and have more everyday functioning complaints (psu2009<u2009.05). Impairment classifications of the two methods were in high agreement; however, more people were classified as impaired using the CR approach compared to the GDS approach. Those impaired according to CR-only showed fewer neurocognitive and functional deficits than the Dually-impaired participants, but more of these deficits than Dually-normal participants. The CR approach may be most appropriate for detecting more subtle forms of neurocognitive impairment. Clinicians and researchers should recognize the strengths and weaknesses of each method when evaluating neurocognitive complications in HIV.

Diagnosing symptomatic HIV-associated neurocognitive disorders: Self-report versus performance-based assessment of everyday functioning

Three types of HIV-associated neurocognitive disorders (HAND) exist that are distinguished by presence and severity of impairment in cognitive and everyday functioning. Although well-validated neurocognitive measures exist, determining impairment in everyday functioning remains a challenge. We aim to determine whether Self-Report measures of everyday functioning are as effective in characterizing HAND as Performance-Based measures. We assessed 674 HIV-infected participants with a comprehensive neurocognitive battery; 233 met criteria for a HAND diagnosis by having at least mild neurocognitive impairment. Functional decline was measured via Self-Report and Performance-Based measures. HAND diagnoses were determined according to published criteria using three approaches to assess functional decline: (1) Self-Report measures only, (2) Performance-Based measures only, and (3) Dual-method combining Self-Report and Performance-Based measures. The Dual-method classified the most symptomatic HAND, compared to either singular method. Singular method classifications were 76% concordant with each other. Participants classified as Performance-Based functionally impaired were more likely to be unemployed and more immunosuppressed, whereas those classified as Self-Report functionally impaired had more depressive symptoms. Multimodal methods of assessing everyday functioning facilitate detection of symptomatic HAND. Singular Performance-Based classifications were associated with objective functional and disease-related factors; reliance on Self-Report classifications may be biased by depressive symptoms.

Substance use is a risk factor for neurocognitive deficits and neuropsychiatric distress in acute and early HIV infection

The acute and early stages of HIV infection (AEH) are characterized by substantial viral replication, immune activation, and alterations in brain metabolism. However, little is known about the prevalence and predictors of neurocognitive deficits and neuropsychiatric disturbances during this period. The present study examined the impact of demographic, HIV disease, and substance use factors on HIV-associated neurocognitive impairment and self-reported neuropsychiatric distress among 46 antiretroviral-naive adults with median duration of infection of 75xa0days relative to a sample of 21 HIV seronegative (HIV−) adults with comparable demographics and risk factors. Participants were administered a brief neurocognitive battery that was adjusted for demographics and assessed executive functions, memory, psychomotor speed, and verbal fluency, as well as the Profile of Mood States, a self-report measure of neuropsychiatric distress. Odds ratios revealed that AEH participants were nearly four times more likely than their seronegative counterparts to experience neurocognitive impairment, particularly in the areas of learning and information processing speed. Similarly, AEH was associated with a nearly fivefold increase in the odds of neuropsychiatric distress, most notably in anxiety and depression. Within the AEH sample, HIV-associated neurocognitive impairment was associated with problematic methamphetamine use and higher plasma HIV RNA levels, whereas neuropsychiatric distress was solely associated with high-risk alcohol use. Extending prior neuroimaging findings, the results from this study indicate that HIV-associated neurocognitive impairment and neuropsychiatric distress are highly prevalent during AEH and are associated with high-risk substance use.

Methamphetamine use and neuropsychiatric factors are associated with antiretroviral non-adherence

Abstract The present study assesses the impact of methamphetamine (METH) on antiretroviral therapy (ART) adherence among HIV+ persons, as well as examines the contribution of neurocognitive impairment and other neuropsychiatric factors [i.e., major depressive disorder (MDD), antisocial personality disorder (ASPD), and attention deficit disorder (ADHD)] for ART non-adherence. We examined HIV+ persons with DSM-IV-diagnosed lifetime history of METH abuse/dependence (HIV+ /METH+ ; n=67) as compared to HIV+ participants with no history of METH abuse/dependence (HIV+ /METH − ; n=50). Ancillary analyses compared these groups with a small group of HIV+ /METH+ persons with current METH abuse/dependence (HIV+ /CU METH+ ; n=8). Non-adherence was defined as self-report of any skipped ART dose in the last four days. Neurocognitive functioning was assessed with a comprehensive battery, covering seven neuropsychological domains. Lifetime METH diagnosis was associated with higher rates of detectable levels of plasma and CSF HIV RNA. When combing groups (i.e., METH+ and METH– participants), univariate analyses indicated co-occurring ADHD, ASPD, and MDD predicted ART non-adherence (ps < 0.10; not lifetime METH status or neurocognitive impairment). A significant multivariable model including these variables indicated that only MDD uniquely predicted ART non-adherence after controlling for the other variables (p<0.05). Ancillary analyses indicated that current METH users (use within 30 days) were significantly less adherent (50% prevalence of non-adherence) than lifetime METH+ users and HIV+ /METH− participants and that neurocognitive impairment was associated with non-adherence (ps < 0.05). METH use disorders are associated with worse HIV disease outcomes and ART medication non-adherence. Interventions often target substance use behaviors alone to enhance antiretroviral treatment outcomes; however, in addition to targeting substance use behaviors, interventions to improve ART adherence may also need to address coexisting neuropsychiatric factors and cognitive impairment to improve ART medication taking.

Cognitive Neurorehabilitation of HIV-associated Neurocognitive Disorders: A Qualitative Review and Call to Action

Despite significant advances in the virologic management of HIV infection over the last two decades, effective treatments for HIV-associated neurocognitive disorders (HAND) remain elusive. While pharmacological interventions have yielded some success in improving neurocognitive outcomes in HIV, there is a dearth of rigorous studies examining the efficacy of cognitive rehabilitation for remediating HIV-associated neurocognitive impairment. This qualitative review summarizes and critiques the emerging literature on cognitive and behavioral treatments for HAND, which provides many reasons for optimism, but also has major limitations that underscore the scope of the work that lies ahead. Considering the notable real-world consequences of HAND, the development, validation, and clinical deployment of cognitive neurorehabilitation interventions tailored to the needs of persons living with HIV infection is a priority for clinical neuroAIDS investigators. In describing potential future directions for this endeavor, particular attention was paid to the application of cognitive neuropsychological principles in developing theory-driven approaches to managing HAND, improving everyday functioning, and enhancing HIV health outcomes.

Human immunodeficiency virus infection heightens concurrent risk of functional dependence in persons with long-term methamphetamine use

Objectives:Disability among long-term methamphetamine (MA) users is multifactorial. This study examined the additive adverse impact of human immunodeficiency virus (HIV) infection, a common comorbidity in MA users, on functional dependence. Methods:A large cohort of participants (N = 798) stratified by lifetime MA-dependence diagnoses (ie, MA+ or MA−) and HIV serostatus (ie, HIV+ or HIV−) underwent comprehensive baseline neuromedical, neuropsychiatric, and functional research evaluations, including assessment of neurocognitive symptoms in daily life, instrumental and basic activities of daily living, and employment status. Results:Independent, additive effects of MA and HIV were observed across all measures of functional dependence, independent of other demographic, psychiatric, and substance-use factors. The prevalence of global functional dependence increased in the expected stepwise fashion across the cohort, with the lowest rates in the MA−/HIV− group (29%) and the highest rates in the MA+/HIV+ sample (69%). The impact of HIV on MA-associated functional dependence was moderated by nadir CD4 count, such that polysubstance use was associated with greater disability among those HIV-infected persons with higher but not lower nadir CD4 count. Within the MA+/HIV+ cohort, functional dependence was reliably associated with neurocognitive impairment, lower cognitive reserve, polysubstance use, and major depressive disorder. Conclusions:HIV infection confers an increased concurrent risk of MA-associated disability, particularly among HIV-infected persons without histories of immune compromise. Directed referrals, earlier HIV treatment, and compensatory strategies aimed at counteracting the effects of low cognitive reserve, neurocognitive impairment, and psychiatric comorbidities on functional dependence in MA+/HIV+ individuals may be warranted.

Real-world impact of neurocognitive deficits in acute and early HIV infection

The acute and early period of HIV-1 infection (AEH) is characterized by neuroinflammatory and immunopathogenic processes that can alter the integrity of neural systems and neurocognitive functions. However, the extent to which central nervous system changes in AEH confer increased risk of real-world functioning (RWF) problems is not known. In the present study, 34 individuals with AEH and 39 seronegative comparison participants completed standardized neuromedical, psychiatric, and neurocognitive research evaluations, alongside a comprehensive assessment of RWF that included cognitive symptoms in daily life, basic and instrumental activities of daily living, clinician-rated global functioning, and employment. Results showed that AEH was associated with a significantly increased risk of dependence in RWF, which was particularly elevated among AEH persons with global neurocognitive impairment (NCI). Among those with AEH, NCI (i.e., deficits in learning and information processing speed), mood disorders (i.e., Bipolar Disorder), and substance dependence (e.g., methamphetamine dependence) were all independently predictive of RWF dependence. Findings suggest that neurocognitively impaired individuals with AEH are at notably elevated risk of clinically significant challenges in normal daily functioning. Screening for neurocognitive, mood, and substance use disorders in AEH may facilitate identification of individuals at high risk of functional dependence who may benefit from psychological and medical strategies to manage their neuropsychiatric conditions.

Identification of an Abbreviated Test Battery for Detection of HIV-Associated Neurocognitive Impairment in an Early-Managed HIV-Infected Cohort

Background HIV-associated neurocognitive disorders (HAND) remain prevalent despite improved antiretroviral treatment (ART), and it is essential to have a sensitive and specific HAND screening tool. Methods Participants were 200 HIV-infected US military beneficiaries, managed early in the course of HIV infection, had few comorbidities, and had open access to ART. Participants completed a comprehensive, seven-domain (16-test), neuropsychological battery (∼120 min); neurocognitive impairment (NCI) was determined using a standardized score derived from demographically adjusted T-scores (global deficit score ≥0.5). Restricting the estimated administration time of the screening battery to <u200a=u200a20 minutes, we examined the sensitivity and specificity of detecting NCI for all possible combinations of 2-, 3-, and 4- tests from the comprehensive battery. Results Participants were relatively healthy (median CD4 count: 546 cells/mm3) with 64% receiving ART. Prevalence of NCI was low (19%). The best 2-test screener included the Stroop Color Test and the Hopkins Verbal Learning Test-Revised (11 min; sensitivityu200a=u200a73%; specificityu200a=u200a83%); the best 3-test screener included the above measures plus the Paced Auditory Serial Addition Test (PASAT; 16 min; sensitivityu200a=u200a86%; specificityu200a=u200a75%). The addition of Action Fluency to the above three tests improved specificity (18 min; sensitivityu200a=u200a86%; specificityu200a=u200a87%). Conclusions Combinations of widely accepted neuropsychological tests with brief implementation time demonstrated good sensitivity and specificity compared to a time intensive neuropsychological test battery. Tests of verbal learning, attention/working memory, and processing speed are particularly useful in detecting NCI. Utilizing validated, easy to administer, traditional neuropsychological tests with established normative data may represent an excellent approach to screening for NCI in HIV.

Preliminary Evidence for Feasibility, Use, and Acceptability of Individualized Texting for Adherence Building for Antiretroviral Adherence and Substance Use Assessment among HIV-Infected Methamphetamine Users.

The feasibility, use, and acceptability of text messages to track methamphetamine use and promote antiretroviral treatment (ART) adherence among HIV-infected methamphetamine users was examined. From an ongoing randomized controlled trial, 30-day text response rates of participants assigned to the intervention (individualized texting for adherence building (iTAB), n = 20) were compared to those in the active comparison condition (n = 9). Both groups received daily texts assessing methamphetamine use, and the iTAB group additionally received personalized daily ART adherence reminder texts. Response rate for methamphetamine use texts was 72.9% with methamphetamine use endorsed 14.7% of the time. Text-derived methamphetamine use data was correlated with data from a structured substance use interview covering the same time period (P < 0.05). The iTAB group responded to 69.0% of adherence reminder texts; among those responses, 81.8% endorsed taking ART medication. Standardized feedback questionnaire responses indicated little difficulty with the texts, satisfaction with the study, and beliefs that future text-based interventions would be helpful. Moreover, most participants believed the intervention reduced methamphetamine use and improved adherence. Qualitative feedback regarding the intervention was positive. Future studies will refine and improve iTAB for optimal acceptability and efficacy. This trial is registered with ClinicalTrials.gov NCT01317277.

Memory-Based Strategies for Antiretroviral Medication Management: An Evaluation of Clinical Predictors, Adherence Behavior Awareness, and Effectiveness

Abstract“Forgetting” is the most commonly endorsed reason for missing an antiretroviral therapy (ART) dose, yet little is known about the prevalence, predictors, and effectiveness of the mnemonic strategies to support ART adherence. The current study assessed 28 self-reported memory-based medication strategies in 233 HIV-infected individuals with 30-day ART adherence measured via the medication event monitoring system. Participants endorsed using multiple (8.7xa0±xa05.6) strategies with the most common being internally-driven. More frequent strategy use was uniquely associated with affective distress, dependent daily functioning, higher non-ART pill burden, and poorer ART adherence. Individuals who used strategies frequently, but perceived them as minimally effective, had more affective, physical, and functional distress. More frequent strategy use was associated with worse ART adherence and was unrelated to perceived effectiveness. Primary reliance on internally-based mnemonic strategies may reflect a lack of awareness of adherence behaviors and may be insufficient to support optimal ART adherence in vulnerable populations.Resumen“Olvidar” es la razón mas común para saltarse una dosis de terapia antirretroviral (ART por sus siglas en Inglés), pero poco se sabe acerca de la prevalencia, factores predictivos y la eficacia de la estrategias mnemónicas que ayudan el ART. El presente estudio evaluó 28 estrategias de memoria que ayudan a recordar tomar los medicamentos. Estas estrategias fueron reportadas por los mismos individuos. El estudio evaluó 233 individuos infectados con VIH durante un periodo de 30 días en los cuales se les monitoreó la adherencia a los medicamentos utilizando el sistema de supervisión de eventos de medicamentos (MEMS, por sus siglas en Inglés). Los participants reportaron usar multiples estrategias (8.7xa0±xa05.6) siendo la más común una estrategia derivada internamente. El uso frecuente de estrategias fue asociado singularmente con el sufrimiento afectivo, dependencia en el funcionanmiento en la vida diaria, la carga asociada a tomar otros medicamentos diferentes al ART, y la pobre aderencia al ART. Los individuos que usaron las estrategias frequentemente, pero que las percibieron como poco efectivas, experimentaron más sufrimiento afectivo, físico y funcional. El uso frequente de las estrategias estuvo asociado con una peor aderencia a los ART y no estuvo relacionado con la percepción de la eficacia. El depender principalmente de estrategias de memoria que son basadas internamente puede reflejar una falta de conciencia sobre los comportamientos de adherencia y puede no ser suficiente para obtener una aderencia optima a los ARTs en poblaciones vulnerables.