BACKGROUND Neurocognitive impairment (NCI) and frailty are more prevalent among persons with HIV (PWH) compared to those without HIV. Frailty and NCI often overlap with one another. Whether frailty precedes declines in neurocognitive function among PWH or vice versa has not been well-established. SETTING AIDS Clinical Trials Group (ACTG) A5322 is an observational cohort study of older PWH. Participants undergo annual assessments for NCI and frailty. METHODS ACTG A5322 participants who developed NCI as indexed by tests of impaired executive functioning and processing speed during the first 3 years were compared to persons who maintained normal cognitive function; those who demonstrated resolution of NCI were compared to those who had persistent NCI. Participants were similarly compared by frailty trajectory. We fit multinomial logistic regression models to assess associations between baseline covariates (including NCI) and frailty, and associations between baseline covariates (including frailty) and NCI. RESULTS 929 participants were included with a median age of 51 years (IQR 46-56). At study entry, 16% had NCI and 6% were frail. Over 3 years, 6% of participants developed NCI; 5% developed frailty. NCI was associated with development of frailty (odds ratio [OR]=2.06; 95% confidence interval [CI]=0.94, 4.48; p=0.07). Further adjustment for confounding strengthened this association (OR=2.79; 95% CI=1.21, 6.43; p=0.02). Baseline frailty however was not associated with NCI development. CONCLUSIONS NCI was associated with increased risk of frailty, but frailty was not associated with development of NCI. These findings suggest that the presence of NCI in PWH should prompt monitoring for the development of frailty and interventions to prevent frailty in this population.

Depression is common following HIV infection and often improves after ART initiation. We aimed to identify distinct dimensions of depression that change following ART initiation in persons with HIV (PWH) with minimal comorbidities (e.g., illicit substance use) and no psychiatric medication use. We expected that dimensional changes in improvements in depression would differ across PWH. In an observational cohort in Rakai, Uganda, 312 PWH (51% male; mean age = 35.6 years) completed the Center for Epidemiologic Studies–Depression (CES-D) scale before and up to 2 years after ART initiation. Twenty-two percent were depressed (CES-D scores ≥ 16) pre-ART that decreased to 8% after ART. All CES-D items were used in a latent class analysis to identify subgroups with similar change phenotypes. Two improvement phenotypes were identified: affective-symptom improvement (n = 58, 19%) and mixed-symptom improvement (effort, appetite, irritability; n = 41, 13%). The affect-improvement subgroup improved on the greatest proportion of symptoms (76%). A third subgroup was classified as no-symptom changes (n = 213, 68%) as they showed no difference is symptom manifestation from baseline (93% did not meet depression criteria) to post-ART. Factors associated with subgroup membership in the adjusted regression analysis included pre-ART self-reported functional capacity, CD4 count, underweight BMI, hypertension, female sex(P’s < 0.05). In a subset of PWH with CSF, subgroup differences were seen on Aβ-42, IL-13, and IL-12. Findings support that depression generally improves following ART initiation; however, when improvement is seen the patterns of symptom improvement differ across PWH. Further exploration of this heterogeneity and its biological underpinning is needed to evaluate potential therapeutic implications of these differences.

There is a paucity of information on neurocognitive dysfunction in individuals with HIV in resource-limited regions, despite the fact that these areas have the greatest burden of infection. HIV-associated neurocognitive disorder (HAND) remains a common complication of HIV despite the use of effective antiretroviral therapy (ART). HAND is a major cause of morbidity of HIV+ individuals and is estimated to be the most prevalent form of neurocognitive impairment worldwide in young adults. This finding has drastic implications for the productivity and social engagement of young adults in the development of industry, education, and healthcare, which is particularly relevant in low-income countries. Building an infrastructure to examine the neurological and neuropsychological characteristics of HIV+ individuals in resource-limited settings (RLS) can advance the understanding of the unique contributing factors of HIV-1 clades in these regions of high prevalence, improve neurological monitoring, explore the CNS HIV reservoir, and provide key information on prevention/interventions to help manage/improve these neurological and neuropsychological complications.

Neuropathic pain and cognitive impairment are among the HIV-related conditions that have most stubbornly resisted amelioration by virally suppressive antiretroviral therapy. Overlaps between the regional brain substrates and mechanisms of neuropathic pain and cognitive disorders are increasingly recognized, yet no studies have examined the longitudinal relationship between these two disorders. Participants in the prospective, observational CNS HIV AntiRetroviral Therapy Effects Research (CHARTER) cohort underwent standardized clinical evaluations for clinical examination findings of distal sensory polyneuropathy, reporting distal neuropathic pain and neurocognitive performance at study entry (baseline) and an average of 12 years later. Change in neuropathic pain and neuropathy status from baseline to follow-up was by self-report and repeat examination, and change in neurocognitive performance was assessed using a previously published summary regression-based change score. Relationships between incident or worsened neuropathic pain and neurocognitive change were evaluated using uni- and multivariable regressions, including age at baseline and other relevant covariates. Participants were 385 people with HIV, 91 (23.6%) females, mean ± standard deviation (SD) age at baseline 43.5 (7.81) years, ethnicity 44.9% African American, 10.6% Hispanic, 42.6% non-Hispanic white and 1.82% other. Baseline median (interquartile range) nadir CD4 was 175 (34 309) cells/µl and current CD4 was 454 (279 639). Incident or worsened distal neuropathic pain occurred in 98 (25.5%) over the follow-up period. People with HIV with incident or worsened distal neuropathic pain had significantly worsened neurocognitive performance at follow-up compared to those without incident or worsened distal neuropathic pain (summary regression-based change score mean ± SD -0.408 ± 0.700 versus -0.228 ± 0.613; P = 0.0158). This effect remained significant when considering viral suppression on antiretroviral therapy, incident diabetes and other covariates as predictors. Overall neurocognitive change related to neuropathic pain was driven primarily by changes in the domains of executive function and speed of information processing. Those with incident distal neuropathy signs did not have neurocognitive worsening, nor did individuals who used opioid analgesics or other pain-modulating drugs such as amitriptyline. Worsened neurocognitive performance in people with HIV was associated with worsened neuropathic pain but not with changes in physical signs of neuropathy, and this was not attributable to therapies for pain or depression or to differences in viral suppression. This finding implies that incident or worsened pain may signal increased risk for neurocognitive impairment, and deserves more investigation, particularly if better pain management might stabilize or improve neurocognitive performance.

We investigated the prevalence and risk factors for frailty among people with HIV (PWH) in rural Uganda (n = 55, 47% male, mean age 44 years). Frailty was defined according to the Fried criteria with self-reported physical activity level replacing the Minnesota Leisure Time Activity Questionnaire. Alternate classifications for physical activity utilized were the sub-Saharan Africa Activity Questionnaire and the International Physical Activity Questionnaire. Eleven participants (19%) were frail. Frail participants were older (p < 0.001), less likely to be on antiretroviral therapy (p = 0.03), and had higher rates of depression (p < .001) and HIV-associated neurocognitive disorder (p = 0.003). Agreement between physical activity measures was sub-optimal. Prevalence of frailty was high among PWH in rural Uganda, but larger sample sizes and local normative data are needed.

OBJECTIVE:Distal sensory polyneuropathy (DSP) is a disabling consequence of human immunodeficiency virus (HIV), leading to poor quality of life and more frequent falls in older age. Neuropathic pain and paresthesia are prevalent symptoms; however, there are currently no known curative treatments and the longitudinal course of pain in HIV-associated DSP is poorly characterized. METHODS:This was a prospective longitudinal study of 265 people with HIV (PWH) enrolled in the CNS HIV Antiretroviral Therapy Effects Research (CHARTER) study with baseline and 12-year follow-up evaluations. Since pain and paresthesia are highly correlated, statistical decomposition was used to separate the two symptoms at baseline. Multivariable logistic regression analyses of decomposed variables were used to determine the effects of neuropathy symptoms at baseline on presence and worsening of distal neuropathic pain at 12-year follow-up, adjusted for covariates. RESULTS:Mean age was 56 ± 8 years, and 21% were female at follow-up. Nearly the entire cohort (96%) was on antiretroviral therapy (ART), and 82% had suppressed (≤50 copies/mL) plasma viral loads at follow-up. Of those with pain at follow-up (n = 100), 23% had paresthesia at the initial visit. Decomposed paresthesia at baseline increased the risk of pain at follow-up (odds ratio [OR] 1.56; 95% confidence interval [CI] 1.18, 2.07), and decomposed pain at baseline predicted a higher frequency of pain at follow-up (OR 1.96 [95% CI 1.51, 2.58]). CONCLUSIONS:Paresthesias are a clinically significant predictor of incident pain at follow-up among aging PWH with DSP. Development of new therapies to encourage neuroregeneration might take advantage of this finding to choose individuals likely to benefit from treatment preventing incident pain.

The causes of cognitive impairment among older HIV+ individuals may overlap with causes among elderly HIV seronegative (HIV-) individuals. The objective of this study was to determine if beta-amyloid (Aβ) deposition measured by [18F] AV-45 (florbetapir) positron emission tomography (PET) is increased in older HIV+ individuals compared to HIV- individuals. Forty-eight HIV+ and 25 HIV- individuals underwent [18F] AV-45 PET imaging. [18F] AV-45 binding to Aβ was measured by standardized uptake value ratios (SUVR) relative to the cerebellum in 16 cortical and subcortical regions of interest. Global and regional cortical SUVRs were compared by (1) serostatus, (2) HAND stage, and (3) age decade, comparing individuals in their 50s and > 60s. There were no differences in median global cortical SUVR stratified by HIV serostatus or HAND stage. The proportion of HIV+ participants in their 50s with elevated global amyloid uptake (SUVR > 1.40) was significantly higher than the proportion in HIV- participants (67% versus 25%, p = 0.04), and selected regional SUVR values were also higher (p < 0.05) in HIV+ compared to HIV- participants in their 50s. However, these group differences were not seen in participants in their 60s. In conclusion, PET imaging found no differences in overall global Aβ deposition stratified by HIV serostatus or HAND stage. Although there was some evidence of increased Aβ deposition in HIV+ individuals in their 50s compared to HIV- individuals which might indicate premature aging, the most parsimonious explanation for this is the relatively small sample size in this cross-sectional cohort study.

BACKGROUND:HIV-infected (HIV+) women seem to be more vulnerable to neurocognitive impairment (NCI) than HIV+ men, perhaps in part due to mental health factors. We assessed the association between elevated depressive symptoms and NCI among HIV+ and HIV-uninfected (HIV-) women and men.SETTING:Women's Interagency HIV Study and Multicenter AIDS Cohort Study.METHODS:Eight hundred fifty-eight HIV+ (429 women; 429 men) and 562 HIV- (281 women; 281 men) completed the Center for Epidemiologic Studies Depression (16 cutoff) Scale and measures of psychomotor speed/attention, executive, and motor function over multiple visits (or time points). Women's Interagency HIV Study and Multicenter AIDS Cohort Study participants were matched according to HIV status, age, race/ethnicity, and education. Generalized linear mixed models were used to examine interactions between biological sex, HIV serostatus, and depression on impairment (T-scores <40) after covariate adjustment.RESULTS:Despite a higher frequency of depression among men, the association between depression and executive function differed by sex and HIV serostatus. HIV+ women with depression had 5 times the odds of impairment on a measure of executive control and inhibition versus HIV- depressed women and 3 times the odds of impairment on that measure versus HIV+ depressed men. Regardless of group status, depression was associated with greater impairment on processing speed, executive (mental flexibility), and motor function (P's < 0.05).CONCLUSIONS:Depression contributes to NCI across a broad range of cognitive domains in HIV+ and HIV- individuals, but HIV+ depressed women show greater vulnerabilities in executive function. Treating depression may help to improve cognition in patients with HIV infection.

BACKGROUND:Neurocognitive impairment remains a common complication of human immunodeficiency virus (HIV) despite effective antiretroviral therapy (ART). We previously reported improved neurocognitive functioning with ART initiation in 7 resource-limited countries for HIV+ participants from the AIDS Clinical Trials Group (ACTG) 5199 International Neurological Study (INS). Here, we apply normative data from the International Neurocognitive Normative Study (INNS) to INS to provide previously unknown rates of neurocognitive impairment. METHODS:The A5199 INS assessed neurocognitive and neurological performance within a randomized clinical trial with 3 arms containing World Health Organization first-line recommended ART regimens (ACTG 5175; PEARLS). The ACTG 5271 INNS collected normative comparison data on 2400 high-risk HIV-negative participants from 10 voluntary counseling and testing sites aligned with INS. Normative comparison data were used to create impairment ratings for HIV+ participants in INS; associations were estimated using generalized estimating equations. RESULTS:Among 860 HIV+ adults enrolled in ACTG 5199, 55% had no neurocognitive impairment at baseline. Mild neurocognitive impairment was found in 25%, moderate in 17%, and severe in 3% of participants. With the initiation of ART, the estimated odds of impairment were reduced 12% (95% confidence interval, 9%, 14%) for every 24 weeks (P < .0001) on ART. Mild impairment dropped slightly and then remained at about 18% out to week 168. CONCLUSIONS:Almost half of HIV+ participants had neurocognitive impairment at baseline before ART, based on local norms. With ART initiation, there were significant overall reductions in neurocognitive impairment over time, especially in those with moderate and severe impairments. CLINICAL TRIALS REGISTRATION:NCT00096824.

Background: During antiretroviral therapy, HIV RNA can be detected in cerebrospinal fluid (CSF) when it is undetectable in plasma, a condition termed 'CSF viral escape'. The aim of the current study was to determine the prevalence and risk factors for CSF viral escape in two large cohorts in the USA. Methods: A total of 1264 HIV-infected volunteers enrolled in two US cohorts at their most recent visit between 2003 and 2011 were included in this cross-sectional analysis if their HIV RNA level in plasma was less than 50 copies/ml while receiving stable antiretroviral therapy (ART) (>6 months) and if they had HIV RNA measured in CSF at their most recent visit between 2003 and 2011. Potential risk factors were identified using univariable and multivariable regression. Results: CSF viral escape was detected in 55 adults (4.4%; 95% CI: 3.4-5.6), who had a median CSF HIV RNA of 155 copies/ml [interquartile range (IQR: 80-283)]. Patients with or without CSF viral escape had similar rates of neurocognitive impairment (38.2 vs. 37.7%; P = 0.91). CSF viral escape was independently associated with the use of ritonavir-boosted protease inhibitors [odds ratio (OR): 2.0; 95% CI: 1.1-3.8] or unboosted atazanavir (OR: 5.1; 95% CI: 1.3-16.1), CSF pleocytosis (OR: 7.6; 95% CI: 4.2-13.7) and abnormal CSF total protein (OR: 2.1; 95% CI: 1.1-3.7). Conclusions: In this large study of aviremic patients receiving ART, CSF viral escape was uncommon and was linked to evidence of central nervous system inflammation and the use of protease inhibitors, but not with worse neurocognitive performance. Copyright (C) 2018 Wolters Kluwer Health, Inc. All rights reserved.

Background: Combination antiretroviral therapy (ART) improves HIV-associated neurocognitive disorder (HAND) stage in the United States where subtype B predominates, but the effect of ART and subtype on HAND stage in individuals in Uganda with subtypes D and A is largely unknown. Setting: A community-based cohort of participants residing in Rakai, Uganda. Methods: Three hundred ninety-nine initially ART-naive HIV-seropositive (HIV+) individuals were followed up over 2 years. Neurological and neuropsychological tests and functional assessments were used to determine HAND stage. Frequency and predictors of HAND and HIV-associated dementia (HAD) were assessed at baseline and at follow-up after ART initiation in 312 HIV+ individuals. HIV subtype was determined from gag and env sequences. Results: At 2-year follow-up, HAD frequency among HIV+ individuals on ART (n = 312) decreased from 13% to 5% (P < 0.001), but the overall frequency of HAND remained unchanged (56%–51%). Subtype D was associated with higher rates of impaired cognition (global deficit score ≥ 0.5) compared with HIV+ individuals with subtype A (55% vs. 24%) (P = 0.008). Factors associated with HAD at baseline were older age, depression, and plasma HIV viral load >100,000 copies/mL. At follow-up, age and depression remained significantly associated with HAD. Conclusions: HIV+ individuals on ART in rural Uganda had a significant decrease in the frequency of HAD, but HAND persists after 2 years on ART. The current guideline of immediate ART initiation after HIV diagnosis is likely to greatly reduce HAD in sub-Saharan Africa. Further studies of the effect of HIV subtype and neurocognitive performance are warranted.

Considerable heterogeneity exists in patterns of neurocognitive change in people with HIV (PWH). We examined heterogeneity in neurocognitive change trajectories from HIV diagnosis to 1–2 years post-antiretroviral therapy (ART). In an observational cohort study in Rakai, Uganda, 312 PWH completed a neuropsychological (NP) test battery at two-time points (ART-naïve, 1–2 years post-ART initiation). All NP outcomes were used in a latent profile analysis to identify subgroups of PWH with similar ART-related neurocognitive change profiles. In a subset, we examined subgroup differences pre-ART on cytokine and neurodegenerative biomarkers CSF levels. We identified four ART-related change subgroups: (1) decline-only (learning, memory, fluency, processing speed, and attention measures), (2) mixed (improvements in learning and memory but declines in attention and executive function measures), (3) no-change, or (4) improvement-only (learning, memory, and attention measures). ART-related NP outcomes that are most likely to change included learning, memory, and attention. Motor function measures were unchanged. Subgroups differed on eight of 34 pre-ART biomarker levels including interleukin (IL)-1β, IL-6, IL-13, interferon-γ, macrophage inflammatory protein-1β, matrix metalloproteinase (MMP)-3, MMP-10, and platelet-derived growth factor-AA. The improvement-only and mixed subgroups showed lower levels on these markers versus the no-change subgroup. These findings provide support for the need to disentangle heterogeneity in ART-related neurocognitive changes, to focus on higher-order cognitive processes (learning, memory, attention) as they were most malleable to change, and to better understand why motor function remained unchanged despite ART treatment. Group differences in pre-ART CSF levels provide preliminary evidence of biological plausibility of neurocognitive phenotyping.

Serum interleukin-6 (IL-6) and D-dimer have been associated with multiple adverse outcomes in HIV-infected (HIV+) individuals, but their association with neuropsychiatric outcomes, including HIV-associated neurocognitive disorder (HAND) and depression, headaches, and peripheral neuropathy have not been investigated. Three hundred ninety-nine HIV+ antiretroviral therapy (ART)-naïve adults in Rakai, Uganda, were enrolled in a longitudinal cohort study and completed a neurological evaluation, neurocognitive assessment, and venous blood draw. Half of the participants had advanced immunosuppression (CD4 count < 200 cells/μL), and half had moderate immunosuppression (CD4 count 350–500 cells/μL). All-cause mortality was determined by verbal autopsy within 2 years. HAND was determined using Frascati criteria, and depression was defined by the Center for Epidemiologic Studies-Depression (CES-D) scale. Neuropathy was defined as the presence of > 1 neuropathy symptom and > 1 neuropathy sign. Headaches were identified by self-report. Serum D-dimer levels were determined using ELISA and IL-6 levels using singleplex assays. Participants were 53% male, mean age 35 + 8 years, and mean education 5 + 3 years. Participants with advanced immunosuppression had significantly higher levels of IL-6 (p < 0.001) and a trend toward higher D-dimer levels (p = 0.06). IL-6 was higher among participants with HAND (p = 0.01), with depression (p = 0.03) and among those who died within 2 years (p = 0.001) but not those with neuropathy or headaches. D-dimer did not vary significantly by any outcome. Systemic inflammation as measured by serum IL-6 is associated with an increased risk of advanced immunosuppression, all-cause mortality, HAND, and depression but not neuropathy or headaches among ART-naïve HIV+ adults in rural Uganda.

BACKGROUND Efavirenz is associated with side effects involving the central nervous system. However, it remains largely unknown whether switching off EFV improves neuropsychological performance. METHODS We utilized data from the Multicenter AIDS Cohort Study (MACS). Participants were categorized by their use of EFV: never on EFV (No EFV), continuously on EFV (No Switch-OFF) and on EFV and then switched off (Switch-OFF). Baseline time points were defined as visits when first neuropsychological data were available. In Analysis 1, we compared neuropsychological and Center for Epidemiological Studies-Depression Scale (CES-D) scores before and after EFV switch in Switch-OFF group, aligning participants at the time of switch. Analysis 2 evaluated trajectory of neuropsychological/CES-D score among the three groups. RESULTS This analysis included 1989 HIV-seropositive participants with neuropsychological data (1675 in No EFV, 44 in No Switch-OFF, and 270 in Switch-OFF group). At baseline, participants had a median age of 37 years, median CD4 cell count 442 cells/μl, and 22.9% viral suppression rate. In Analysis 1, neuropsychological and CES-D scores did not show clinically significant changes over 2 years prior to and 4 years after switch in Switch-OFF group. In Analysis 2, trends in neuropsychological and CES-D scores in the three different groups did not show significant differences during a median of 3.2 years of follow-up. CONCLUSION Discontinuation of EFV is not associated with changes in neuropsychological performance or severity of depression in men. Furthermore, we did not observe differences among participants who were never on EFV, continuously on EFV, and on EFV and then switched off.

Objectives:Studies of neurocognitively elite older adults, termedSuperAgers, have identified clinical predictors and neurobiological indicators of resilience against age-related neurocognitive decline. Despite rising rates of older persons living with HIV (PLWH), SuperAging (SA) in PLWH remains undefined. We aimed to establish neuropsychological criteria for SA in PLWH and examined clinically relevant correlates of SA.Methods: 734 PLWH and 123 HIV-uninfected participants between 50 and 64 years of age underwent neuropsychological and neuromedical evaluations. SA was defined as demographically corrected (i.e., sex, race/ethnicity, education) global neurocognitive performance within normal range for 25-year-olds. Remaining participants were labeled cognitively normal (CN) or impaired (CI) based on actual age. Chi-square and analysis of variance tests examined HIV group differences on neurocognitive status and demographics. Within PLWH, neurocognitive status differences were tested on HIV disease characteristics, medical comorbidities, and everyday functioning. Multinomial logistic regression explored independent predictors of neurocognitive status.Results:Neurocognitive status rates and demographic characteristics differed between PLWH (SA=17%; CN=38%; CI=45%) and HIV-uninfected participants (SA=35%; CN=55%; CI=11%). In PLWH, neurocognitive groups were comparable on demographic and HIV disease characteristics. Younger age, higher verbal IQ, absence of diabetes, fewer depressive symptoms, and lifetime cannabis use disorder increased likelihood of SA. SA reported increased independence in everyday functioning, employment, and health-related quality of life than non-SA.Conclusions:Despite combined neurological risk of aging and HIV, youthful neurocognitive performance is possible for older PLWH. SA relates to improved real-world functioning and may be better explained by cognitive reserve and maintenance of cardiometabolic and mental health than HIV disease severity. Future research investigating biomarker and lifestyle (e.g., physical activity) correlates of SA may help identify modifiable neuroprotective factors against HIV-related neurobiological aging. (JINS, 2019,25, 507–519)

We investigated whether vitamin D is associated with HIV-associated neurocognitive disorder (HAND). HIV-infected (HIV+) antiretroviral therapy (ART)-naïve adults in rural Uganda underwent a neurocognitive battery for determination of HAND stage at baseline and after 2 years. Baseline serum 25-hydroxyvitamin D (25OH-D) and serum and cerebrospinal fluids (CSF) vitamin D-binding protein (VDBP) were obtained. Of the 399 participants, 4% (n = 16) were vitamin D deficient (25OH-D < 20 ng/mL). There was no association between 25OH-D, serum or CSF VDBP, and HAND stage at baseline or follow-up. Future studies in a population with higher levels of vitamin D deficiency may be warranted.

Objective: The presentation of cognitive impairments in HIV-infected individuals has transformed since the introduction of antiretroviral therapies. Although the overall prevalence of cognitive impairments has not changed considerably, frank dementia is now infrequent, and milder forms of cognitive impairments predominate. Mechanistic insights to the underlying causes of these residual cognitive impairments have been elusive, in part due to the heterogenous etiology of cognitive dysfunction in this population. Here, we sought to categorize longitudinal change in HIV-infected patients based on the performance in specific cognitive domains. Design: This study consisted of 193 participants from the CHARTER cohort with detailed demographic, clinical, and neuropsychological testing data obtained from 2 study visits interspersed by ∼6 months. Cognitive testing assessed executive function, learning and delayed recall, working memory, verbal fluency, speed of information processing, and motor skills. Change scores were calculated for each domain between the 2 study visits. Dimension reduction and clustering was accomplished by principal component analysis of change scores and k-means clustering to identify cognitive domains that group together and groups of subjects with similar patterns of change. Results: We identified 4 distinct cognitive change phenotypes that included declines in: (1) verbal fluency, (2) executive function (3) learning and recall, and (4) motor function, with approximately equal numbers of participants in each phenotype. Conclusions: Each of the 4 cognitive change phenotypes identify deficits that imply perturbations in specific neural networks. Future studies will need to validate if cognitive change phenotypes are associated with alterations in associated neural pathways.

Context: Perinatal HIV infection has adverse cognitive consequences into adolescence. However, there are no screening tools that assess risk for HIV-associated neurocognitive disorders in adolescent populations. Such screening tools are needed urgently for clinical care in resource-poor settings with a high prevalence of HIV. Objective: To investigate the performance of the International HIV Dementia Scale (IHDS) as a screening tool for HIV-associated neurocognitive disorders in perinatally adolescents. Design: The current study is a quantitative, quasiexperimental design. Methods: Perinatally HIV-infected adolescents aged 9-12 years were recruited from community health clinics into the Cape Town Adolescent Antiretroviral Cohort; matched HIV-negative controls from the same communities were enrolled. Each participant completed the IHDS and a comprehensive neuropsychological battery. The adult version of the IHDS was performed, except for two minor modifications. We evaluated the diagnostic validity of this modified instrument, the youth-IHDS (y-IHDS), using a four-step process that included sensitivity and specificity calculations, and generating receiver operating characteristic curves. Validity was measured against the youth HIV-associated diagnostic criteria. Results: At a cut-off score of 10 or less, the y-IHDS demonstrated good sensitivity (94%) but poor specificity (24%) for detecting all forms of neurocognitive disorders, with an acceptable area under the curve value of 0.695. Conclusion: The y-IHDS requires minimal resources and is based on a screening tool for adult HIV-associated cognitive disorders that is already widely used globally. Hence, this brief, cost-efficient, and valid screening tool may be a useful addition for clinicians working in resource-poor contexts in which adolescent HIV is highly prevalent. Copyright (C) 2019 Wolters Kluwer Health, Inc. All rights reserved.

May 8, 2019April 9, 2019Free AccessNeurofilament Light Chain Protein Levels in HIV Positive Subjects with Neuropathy (P4.9-005)Anne Damian, Richard Skolasky, Henrik Zetterberg, Kaj Blennow, Cornelia Demsky, Magnus Gisslen, Justin McArthur, and Ned SacktorAuthors Info & AffiliationsApril 9, 2019 issue92 (15_supplement)https://doi.org/10.1212/WNL.92.15_supplement.P4.9-005 Letters to the Editor

BACKGROUND:The long-term effects of marijuana on cognition, particularly in the context of HIV is not clear, as extant research shows mixed findings. OBJECTIVE:To determine associations between current and cumulative exposure to marijuana and changes in cognitive processing speed and flexibility in 788 HIV-seropositive (HIV+) and 1,132 HIV-seronegative (HIV-) men followed for up to 17 years in the Multicenter AIDS Cohort Study. RESULTS:Among HIV+ men only, current daily marijuana use compared to none-use, was significantly associated with a greater annual percentage decline in cognitive processing speed assessed with the Trail Making Test A (TMTA) (β=-0.41, 95% confidence interval (CI): -0.88, -0.03, p=0.03)] and Symbol Digit Modalities Test (SDMT) (β= -0.14, 95% CI: -0.28, -0.01, p=0.04). Further, monthly marijuana use was associated with greater annual percentage decline in cognitive flexibility assessed with the Trail Making Test B (TMTB) (β= -0.70, 95% CI: -1.34, -0.05; p=0.03] and cognitive processing speed (SDMT) (β= -0.21, 95% CI: -0.40, -0.01, p=0.03). Among the HIV- men only, each 5-marijuana use-years (equivalent to 5-years of daily marijuana use) was significantly associated with a 0.17 annual percentage decline in cognitive processing speed only (TMTA) (β= -0.18, 95% CI: -0.36, -0.01; p=0.04). CONCLUSIONS:Our findings suggest that marijuana use, particularly current use, may be associated with worse cognitive processing speed, but the magnitude of the estimates was not clinically meaningful.