Lack of Association of Vascular Risk Factors with HIV-Associated Neurocognitive Disorders in cART-Treated Adults Aged ≥ 50 Years in Tanzania.

HIV-associated neurocognitive disorders (HAND) are highly prevalent in those ageing with HIV. High-income country data suggest that vascular risk factors (VRFs) may be stronger predictors of HAND than HIV-disease severity, but data from sub-Saharan Africa are lacking. We evaluated relationships of VRFs, vascular end-organ damage and HAND in individuals aged ≥ 50 in Tanzania. c-ART-treated individuals were assessed for HAND using consensus criteria. The prevalence of VRFs and end organ damage markers were measured. The independent associations of VRFs, end organ damage and HAND were examined using multivariable logistic regression. Data were available for 153 individuals (median age 56, 67.3% female). HAND was highly prevalent (66.7%, 25.5% symptomatic) despite well-managed HIV (70.5% virally suppressed). Vascular risk factors included hypertension (34%), obesity (10.5%), hypercholesterolemia (33.3%), diabetes (5.3%) and current smoking (4.6%). End organ damage prevalence ranged from 1.3% (prior myocardial infarction) to 12.5% (left ventricular hypertrophy). Measured VRFs and end organ damage were not independently associated with HAND. The only significant association was lower diastolic BP (p 0.030, OR 0.969 (0.943-0.997). Our results suggest that vascular risk factors are not major drivers of HAND in this setting. Further studies should explore alternative aetiologies such as chronic inflammation.

Prevalence and 1-year incidence of HIV-associated neurocognitive disorder (HAND) in adults aged ≥50 years attending standard HIV clinical care in Kilimanjaro, Tanzania.

OBJECTIVES: HIV-associated neurocognitive disorders (HANDs) are prevalent in older people living with HIV (PLWH) worldwide. HAND prevalence and incidence studies of the newly emergent population of combination antiretroviral therapy (cART)-treated older PLWH in sub-Saharan Africa are currently lacking. We aimed to estimate HAND prevalence and incidence using robust measures in stable, cART-treated older adults under long-term follow-up in Tanzania and report cognitive comorbidities. DESIGN: Longitudinal study. PARTICIPANTS: A systematic sample of consenting HIV-positive adults aged ≥50 years attending routine clinical care at an HIV Care and Treatment Centre during March-May 2016 and followed up March-May 2017. MEASUREMENTS: HAND by consensus panel Frascati criteria based on detailed locally normed low-literacy neuropsychological battery, structured neuropsychiatric clinical assessment, and collateral history. Demographic and etiological factors by self-report and clinical records. RESULTS: In this cohort (n = 253, 72.3% female, median age 57), HAND prevalence was 47.0% (95% CI 40.9-53.2, n = 119) despite well-managed HIV disease (Mn CD4 516 (98-1719), 95.5% on cART). Of these, 64 (25.3%) were asymptomatic neurocognitive impairment, 46 (18.2%) mild neurocognitive disorder, and 9 (3.6%) HIV-associated dementia. One-year incidence was high (37.2%, 95% CI 25.9 to 51.8), but some reversibility (17.6%, 95% CI 10.0-28.6 n = 16) was observed. CONCLUSIONS: HAND appear highly prevalent in older PLWH in this setting, where demographic profile differs markedly to high-income cohorts, and comorbidities are frequent. Incidence and reversibility also appear high. Future studies should focus on etiologies and potentially reversible factors in this setting.

Contemporary trends in HIV-associated neurocognitive disorders in Ghana.

BACKGROUND: Widespread introduction of early combination antiretroviral therapy (cART) for People Living with HIV (PLWH) will influence the burden, profile, and trajectory of HIV-associated neurocognitive disorders (HAND) in the 21st century. OBJECTIVES: To assess the prevalence and trajectory of HAND among PLWH in a Ghanaian tertiary medical center. METHODS: We analyzed the dataset of a study involving PLWH established on cART (n = 256) and PLWH not initially on cART (n = 244). HIV-negative individuals (n = 246) served as normative controls for neurocognitive assessments. HAND was defined according to the Frascati criteria into asymptomatic neurocognitive impairment (ANI), mild neurocognitive disorder (MND) and HIV-associated dementia (HAD) at enrollment and at month 12. Multivariate logistic regression models were fitted to identify factors associated with HAND. RESULTS: Among PLWH on cART, 21.5%, 3.5% and 0.0% had ANI, MND and HAD respectively compared with 20.1%, 9.8% and 2.0% among PLWH cART naïve, p < 0.0001. Overall, 71.6%, 20.8%, 6.6% and 1.0% had no cognitive impairment, ANI, MND and HAD at baseline. Among participants who completed month 12 follow-up, 55.2% had no cognitive impairment, 43.5%, 1.2%, 0.0% had ANI, MND and HAD respectively, p < 0.0001. Adjusted odds ratio (95% CI) of six independent predictors of HAND at month 12 were no education (3.29;1.81-6.00), stage 4 disease (4.64;1.37-15.69), hypertension (2.28;1.10-4.73), nevirapine use (2.05;1.04-4.05), baseline viral load (0.66;0.56-0.77), and cigarette use (0.10; 0.03-0.42). CONCLUSION: Most Ghanaian patients in the post-cART era with HAND had mild neurocognitive impairments. The impact of hypertension on progression of HAND warrants further evaluation in our settings.

Prevalence of HIV-associated neurocognitive disorder (HAND) in Turkey and assessment of Addenbrooke's Cognitive Examination Revised (ACE-R) test as a screening tool.

OBJECTIVES: We aimed to assess the Addenbrooke's Cognitive Examination Revised (ACE-R) and three questions (3Qs, European Aids Clinical Society Guidelines) as potential screening tools for HIV-associated neurocognitive disorder (HAND). In addition, we tried to determine the prevalence and associated factors for HAND among people living with HIV (PLWH) in Turkey. METHODS: Persons living with HIV were enrolled from two teaching hospitals between March 2018 and September 2018. Participants underwent screening tools, a neuropsychological test battery (NTB) and an assessment of activities of daily living. HAND was diagnosed according to Frascati's criteria and applying the Global Deficit Score (GDS) approach. A receiver operating characteristic (ROC) curve analysis was performed to compare the predictive accuracy of ACE-R to that of the NP test battery. Factors associated with HAND were evaluated using multivariate logistic regression analysis. RESULTS: The study sample included 162 participants (94% male). The HAND prevalence was 45.7% [asymptomatic neurocognitive impairment (ANI), 37.7%; mild neurocognitive disorder (MND), 7.4%; HIV-associated dementia (HAD), 0.6%] according to the Frascati criteria and 31.5% (ANI, 25.9%; MND, 4.9%; HAD, 0.6%) using the GDS. In the ROC analysis, the ACE-R showed an area under the curve of 0.68 at a cut-off score of 89. The sensitivity, specificity and correct classification rate of screening tests for HAND diagnosis were as follows: ACE-R (62.2%, 67%, 64.8%) and 3Qs (10.8%, 88.6%, 53%). In multivariate analysis, only education level (adjusted odds ratio [aOR] = 0.84, 95% CI: 0.76-0.92, P ≤ 0.001) was an independent risk factor for HAND. CONCLUSIONS: HAND is a common comorbidity in PLWH in Turkey. The sensitivities and specificities of 3Qs and the ACE-R as screening tools are lower than desired.

Is the use of the QPC cognitive complaints questionnaire relevant for the screening strategy of HIV-Associated neurocognitive disorders?

BACKGROUND: The screening strategy for HIV-Associated Neurocognitive Disorders (HAND) is challenging. The French Expert Report recommend the use of the Cognitive Complaints Questionnaire (QPC) and the Montreal Cognitive assessment. However, the QPC has never been studied in People Living with HIV (PLWH). This study aims to determine the degree of agreement between QPC and the presence of HAND according to Frascati criteria, established by a battery of neuropsychological tests. METHODS: Data from patients who performed both a QPC and a battery of neuropsychological tests over a six-month follow-up period were evaluated retrospectively. RESULTS: A total of 121 patients were selected, with a median age of 53.1 years old. Among participants, 92.6% had an undetectable plasma viral load, 49.6% had a nadir CD4 less than 200/mm3 and 23.1% had a CDC stage C. Median CD4 cell count was 686/mm3. Prevalence of HAND was 57%, including 28.9% of Asymptomatic Neurocognitive Impairment, 24.8% of Mild Neurocognitive Disorder and 3.3% of HIV-associated Dementia. This analyze shows no agreement between QPC and HIV-associated neurocognitive disorders (kappa = -0.007). CONCLUSIONS: The QPC is not relevant in the screening for HAND. Thus, it urges to develop a specific tool to assess cognitive complaints among PLWH.

Asymptomatic neurocognitive impairment is a risk for symptomatic decline over a 3-year study period.

OBJECTIVE: To examine whether persons with asymptomatic neurocognitive impairment (ANI) were more likely to show progression to mild neurocognitive disorder or HIV-associated dementia than those who were neuropsychologically normal (NP-N). DESIGN: Longitudinal observational cohort study. METHODS: Study sample included 720 HIV-1 seropositive persons (317 with ANI and 403 NP-N) receiving care in Toronto, Canada [83% were on antiretroviral treatment; 71% had undetectable (<50 copies/ml) plasma HIVRNA]. Neuropsychological assessments were conducted at 12 months intervals for a median follow-up time of 34 months. Neuropsychological data were corrected for age, education, sex, and race/ethnicity, and corrected for practice effect at follow-ups. Progression to mild neurocognitive disorder and HIV-associated dementia at each time point was determined using the Global Deficit Score and presence of cognitive symptoms. RESULTS: Over the follow-up period, 170 individuals (24%) progressed to symptomatic HIV-associated neurocognitive disorders (HAND). Persons with ANI were more likely to progress to symptomatic HAND than persons with NP-N after adjusting for baseline and time-varying confounders (adjusted hazards ratio: 1.88; 95% confidence interval: 1.37-2.60; P < 0.001). Female sex, depression, and cigarette smoking were associated with higher risk of progression to symptomatic HAND, but traditional HIV markers and antiretroviral treatment were not. CONCLUSION: ANI is associated with a two-fold increased risk of progression to symptomatic HAND in a cohort with universal healthcare access. This represents the largest replication of comparable US results. Reproducibility of these findings indicate that routine monitoring of persons with ANI and exploration of clinical interventions to prevent or delay progression to symptomatic HAND are imperative. SEARCH TERMS: HIV, HAND, HIV-associated dementia, cohort study, replicability, reproducibility.

Screening for HIV-Associated Neurocognitive Disorders: Sensitivity and Specificity.

HIV-associated neurocognitive disorder (HAND) remains prevalent among people living with HIV (PLWH), especially the mild forms, even those with well-controlled HIV. Recommendations from the literature suggest routine and regular screening for HAND to detect it early and manage it effectively and adjust treatments, if warranted, when present. However, screening for HAND is not routinely done, as there are no current guidelines on when to screen and which test or tests to use. Furthermore, many of the available screening tools for HAND often cannot accurately detect the mild forms of HAND and require highly trained healthcare professionals to administer and score the tests, a requirement that is not feasible for those low- and middle-income countries with the highest HIV incidence and prevalence rates. The purpose of this chapter was to review recent research on screening tests to detect HAND and report on the strengths, limitations, and psychometric properties of those tests to detect HAND.

Unraveling neuroHIV in the Presence of Substance Use Disorders.

This special issue contains 10 invited review papers that highlighted and extended the presentations at the NIDA-sponsored workshop "Unraveling NeuroAIDS in the Presence of Substance Use Disorders" at the 25th Society on NeuroImmune Pharmacology conference in 2019. The topics covered by these papers focused on the interactive, additive or synergistic effects of substance use disorders (SUD) with HIV infection on the immune system and on neuropathogenesis. These papers reviewed four categories of substances of abuse (opioids, tobacco, stimulants, and cannabis) and how comorbid HIV infection (including models with HIV proteins, HIV transgenic rodent models and SIV) might further impact the dysregulated dopaminergic and immune systems, and the subsequent neuropathogenesis and behavioral disorders known as HIV-associated neurological disorders (HAND). These reviews provided detailed background knowledge regarding how each of these addictive substances and HIV individually or collectively affected the immune system at the cellular, molecular and system levels, and the subsequent clinical and behavioral outcomes. The authors also identified gaps, confounds or constraints in the current disease models and approaches, and proposed future research directions.

Machine learning models reveal neurocognitive impairment type and prevalence are associated with distinct variables in HIV/AIDS.

Neurocognitive impairment (NCI) among HIV-infected patients is heterogeneous in its reported presentations and frequencies. To determine the prevalence of NCI and its associated subtypes as well as predictive variables, we investigated patients with HIV/AIDS receiving universal health care. Recruited adult HIV-infected subjects underwent a neuropsychological (NP) test battery with established normative (sex-, age-, and education-matched) values together with assessment of their demographic and clinical variables. Three patient groups were identified including neurocognitively normal (NN, n = 246), HIV-associated neurocognitive disorders (HAND, n = 78), and neurocognitively impaired-other disorders (NCI-OD, n = 46). Univariate, multiple logistic regression and machine learning analyses were applied. Univariate analyses showed variables differed significantly between groups including birth continent, quality of life, substance use, and PHQ-9. Multiple logistic regression models revealed groups again differed significantly for substance use, PHQ-9 score, VACS index, and head injury. Random forest (RF) models disclosed that classification algorithms distinguished HAND from NN and NCI-OD from NN with area under the curve (AUC) values of 0.87 and 0.77, respectively. Relative importance plots derived from the RF model exhibited distinct variable rankings that were predictive of NCI status for both NN versus HAND and NN versus NCI-OD comparisons. Thus, NCI was frequently detected (33.5%) although HAND prevalence (21%) was lower than in several earlier reports underscoring the potential contribution of other factors to NCI. Machine learning models uncovered variables related to individual NCI types that were not identified by univariate or multiple logistic regression analyses, highlighting the value of other approaches to understanding NCI in HIV/AIDS.

Determinants of cognitive health in Indonesian HIV patients beginning antiretroviral therapy.

Cognitive impairment has been described in people living with HIV and stable on antiretroviral therapy (ART), but has not been monitored in young adults beginning ART with a high burden of cytomegalovirus. We recruited 80 subjects beginning ART with < 200 CD4 T cells/µL in Jakarta, Indonesia. Cognitive function (Z-scores) began low but improved on ART, stabilizing after 6 months with improvements in all domains except memory function. The burden of cytomegalovirus persisting on ART (assessed via antibody levels) correlated inversely with Z-scores (notably memory function) at baseline. In linear mixed models, improvements in Z-scores were influenced by age, education, and CD4 T cell counts.

Cannabis Exposure is Associated With a Lower Likelihood of Neurocognitive Impairment in People Living With HIV.

BACKGROUND: Aging and HIV have adverse effects on the central nervous system, including increased inflammation and neural injury and confer risk of neurocognitive impairment (NCI). Previous research suggests the nonacute neurocognitive effects of cannabis in the general population are adverse or null. However, in the context of aging and HIV, cannabis use may exert beneficial effects due to its anti-inflammatory properties. In the current study, we examined the independent and interactive effects of HIV and cannabis on NCI and the potential moderation of these effects by age. METHODS: Participants included 679 people living with HIV (PLHIV) and 273 people living without HIV (HIV-) (18-79 years old) who completed neurocognitive, neuromedical, and substance use assessments. NCI was defined as a demographically corrected global deficit score ≥ 0.5. Logistic regression models examined the effects of age, HIV, cannabis (history of cannabis substance use disorder and cannabis use in past year), and their 2-way and 3-way interactions on NCI. RESULTS: In logistic regression models, only a significant interaction of HIV X cannabis was detected (P = 0.02). Among PLHIV, cannabis was associated with a lower proportion of NCI (odds ratio = 0.53, 95% confidence interval = 0.33-0.85) but not among HIV- individuals (P = 0.40). These effects did not vary by age. CONCLUSIONS: Findings suggest cannabis exposure is linked to a lower odds of NCI in the context of HIV. A possible mechanism of this result is the anti-inflammatory effect of cannabis, which may be particularly important for PLHIV. Further investigations are needed to refine the effects of dose, timing, and cannabis compound on this relationship, which could inform guidelines for cannabis use among populations vulnerable to cognitive decline.

Bidirectional Associations among Nicotine and Tobacco Smoke, NeuroHIV, and Antiretroviral Therapy.

People living with HIV (PLWH) in the antiretroviral therapy (ART) era may lose more life-years to tobacco use than to HIV. Yet, smoking rates are more than twice as high among PLWH than the general population, contributing not just to mortality but to other adverse health outcomes, including neurocognitive deficits (neuroHIV). There is growing evidence that synergy with chronic inflammation and immune dysregulation that persists despite ART may be one mechanism by which tobacco smoking contributes to neuroHIV. This review will summarize the differential effects of nicotine vs tobacco smoking on inflammation in addition to the effects of tobacco smoke components on HIV disease progression. We will also discuss biomarkers of inflammation via neuroimaging as well as biomarkers of nicotine dependence (e.g., nicotine metabolite ratio). Tobacco smoking and nicotine may impact ART drug metabolism and conversely, certain ARTs may impact nicotine metabolism. Thus, we will review these bidirectional relationships and how they may contribute to neuroHIV and other adverse outcomes. We will also discuss the effects of tobacco use on the interaction between peripheral organs (lungs, heart, kidney) and subsequent CNS function in the context of HIV. Lastly, given the dramatic rise in the use of electronic nicotine delivery systems, we will discuss the implications of vaping on these processes. Despite the growing recognition of the importance of addressing tobacco use among PLWH, more research is necessary at both the preclinical and clinical level to disentangle the potentially synergistic effects of tobacco use, nicotine, HIV, cognition and immune dysregulation, as well as identify optimal approaches to reduce tobacco use. Graphical Abstract Proposed model of the relationships among HIV, ART, smoking, inflammation, and neurocognition. Solid lines represent relationships supported by evidence. Dashed lines represent relationships for which there is not enough evidence to make a conclusion. (a) HIV infection produces elevated levels of inflammation even among virally suppressed individuals. (b) HIV is associated with deficits in cognition function. (c) Smoking rates are higher among PLWH, compared to the general population. (d) The nicotine metabolite ratio (NMR) is associated with smoking behavior. (e) HIV and tobacco use are both associated with higher rates of psychiatric comorbidities, such as depression, and elevated levels of chronic stress. These factors may represent other mechanisms linking HIV and tobacco use. (f) The relationship between nicotine, tobacco smoking, and inflammation is complex, but it is well-established that smoking induces inflammation; the evidence for nicotine as anti-inflammatory is supported in some studies, but not others. (g) The relationship between tobacco use and neurocognition may differ for the effects of nicotine (acute nicotine use may have beneficial effects) vs. tobacco smoking (chronic use may impair cognition). (h) Elevated levels of inflammation may be associated with deficits in cognition. (i) PLWH may metabolize nicotine faster than those without HIV; the mechanism is not yet known and the finding needs validation in larger samples. We also hypothesize that if HIV-infection increases nicotine metabolism, then we should observe an attenuation effect once ART is initiated. (j) It is possible that the increase in NMR is due to ART effects on CYP2A6. (k) We hypothesize that faster nicotine metabolism may result in higher levels of inflammation since nicotine has anti-inflammatory properties.

Characteristics of Motor Dysfunction in Longstanding Human Immunodeficiency Virus.

BACKGROUND: Cognitive dysfunction in human immunodeficiency virus (HIV) has decreased, but milder forms of HIV-associated neurocognitive disorders (HAND) persist along with motor dysfunction. The HIV Motor Scale (HMS) is a validated tool that captures motor abnormalities on routine neurologic examination and which is associated with cognitive impairment in HIV. In this study, we applied a modified HMS (MHMS) to a nationwide cohort of people with longstanding HIV to characterize and understand the factors contributing to motor dysfunction. METHODS: The National NeuroAIDS Tissue Consortium is a nationwide longitudinal cohort study. Participants undergo regular assessments including neurological examination, neuropsychological testing, and immunovirologic data collection. Data from examinations were used to calculate the MHMS score, which was then correlated with history of AIDS-related central nervous system (CNS) disorders (ARCD; eg, prior CNS opportunistic infection), cerebrovascular disease (CVD), and HAND. RESULTS: Sixty-nine percent of participants showed an abnormality on the MHMS, with 27% classified as severe. Results did not vary based on demographic or immunologic variables. The most common abnormalities seen were gait (54%), followed by coordination (39%) and strength (25%), and these commonly co-occurred. CVD (P = .02), history of ARCD (P = .001), and HAND (P = .001) were all associated with higher (ie, worse) HMS in univariate analyses; CVD and ARCD persisted in multivariate analyses. CVD was also marginally associated with symptomatic HAND. CONCLUSIONS: Complex motor dysfunction remains common in HIV and is associated with CVD, ARCD, and to a lesser extent, HAND. Future studies are needed to understand the longitudinal trajectory of HIV-associated motor dysfunction, its neural substrates, and impact on quality of life.

High prevalence of neurocognitive disorders observed among adult people living with HIV/AIDS in Southern Ethiopia: A cross-sectional study.

BACKGROUND: Comprehensive care given to people living with HIV/AIDS is improving over time; however, their concurrent cognitive illness is still ignored, under screened and treated particularly in developing countries. And this problem is also striking in Ethiopia. Therefore, the objective of this study was to assess HIV-associated neurocognitive disorders and associated factors among adult people living with HIV/AIDS. METHODS: An institution based cross sectional study was conducted from April to May, 2017 at Gamo Gofa zone public Hospitals. International HIV Dementia Scale was used to screen HIV associated neurocognitive disorders. Logistic regression analysis was used to assess predictors of neurocognitive disorders. RESULT: A total of 684 study participants were included in this study with a response rate of 98%. Among them, 56% were females while 44% were males. The mean (±SD) age of the participants was 38.8±8.8years. The screening prevalence of HIV-associated neurocognitive disorder was 67.1% (95% CI; 63.6, 70.5). Body mass index 16 kg/m2 (AOR 4.389 (1.603-12.016)), being married (AOR 0.377 (0.213-0.666), unemployment status (AOR 3.181 (1.752-5.777) and being in WHO clinical stage T3 category/advancing stages of the disease (AOR 3.558 (1.406-9.006) were the key predictors of HIV-associated neurocognitive disorders among people living with HIV/AIDS. CONCLUSION: In this study the screening prevalence of HIV-associated neurocognitive disorder is higher than the earlier reports in Ethiopia and Africa. This indicates that early screening strategies and policies for cognitive health in people living with HIV/AIDS should be given a top priority.

Neurocognitive Impairment Risk Among Individuals With Multiple Drug-Resistant Tuberculosis and Human Immunodeficiency Virus Coinfection: Implications for Systematic Linkage to and Retention of Care in Tuberculosis/Human Immunodeficiency Virus Treatment.

Although neurocognitive impairment (NCI) is a well-recognized challenge in human immunodeficiency virus (HIV), there is little evidence regarding it among individuals with multiple drug-resistant tuberculosis (MDR-TB) within HIV endemic sub-Saharan Africa. The extent of NCI risk, particularly HIV-associated neurocognitive disorders (HAND) risk, was investigated in 200 microbiologically confirmed inpatients with MDR-TB at a TB-specialist hospital in KwaZulu-Natal Province, South Africa. Within this population, the prevalence of HIV coinfection, major depressive episode, and substance use disorder was 89.50%, 10.50%, and 7.00%, respectively. After excluding individuals with major depressive episode/substance use disorder and monoinfection (i.e., MDR-TB without HIV), the prevalence of HAND risk was 43.5%. Older and low-income individuals had significantly greater odds of HAND risk, whereas those with family members/relatives who work(ed) in the health services had lower odds. The role of timely linkage to and retention of care in TB/HIV treatment to offset cognitive decline in MDR-TB/HIV coinfected individuals needs to be investigated further.

Impaired Neurocognitive Performance and Mortality in HIV: Assessing the Prognostic Value of the HIV-Dementia Scale.

This study examined whether global HIV-associated neurocognitive impairment (NCI), assessed with the HIV-Dementia Scale (HDS), predicted mortality in an ethnically diverse sample of 209 HIV-positive adults. Participants were predominantly in the mid-range of illness at baseline, and followed over 13-years. At baseline, 31 (15%) participants scored in the NCI range (HDS ≤ 10); 58 (28%) died during follow-up. Baseline NCI was significantly associated with earlier mortality (HR = 2.10, 95% CI [1.10-4.00]) independent of sociodemographic and HIV disease-related covariates. Less errors on the antisaccade task, an index of executive/attention control, was the only HDS subtest predicting earlier mortality (HR = 0.72, 95% CI [0.58-0.90]). In the absence of an AIDS-defining condition, NCI, particularly in the executive/attention domain, is an independent prognostic marker of mortality in a diverse HIV-positive cohort. These findings highlight the clinical utility of brief cognitive screening measures in this population.

Pathogenesis of age-related HIV neurodegeneration.

People over the age of 50 are the fastest growing segment of the HIV-infected population in the USA. Although antiretroviral therapy has remarkable success controlling the systemic HIV infection, HIV-associated neurocognitive disorder (HAND) prevalence has increased or remained the same among this group, and cognitive deficits appear more severe in aged patients with HIV. The mechanisms of HAND in the aged population are not completely understood; a leading hypothesis is that aged individuals with HIV might be at higher risk of developing Alzheimer's disease (AD) or one of the AD-related dementias (ADRD). There are a number of mechanisms through which chronic HIV disease alone or in combination with antiretroviral therapy and other comorbidities (e.g., drug use, hepatitis C virus (HCV)) might be contributing to HAND in individuals over the age of 50 years, including (1) overlapping pathogenic mechanisms between HIV and aging (e.g., decreased proteostasis, DNA damage, chronic inflammation, epigenetics, vascular), which could lead to accelerated cellular aging and neurodegeneration and/or (2) by promoting pathways involved in AD/ADRD neuropathogenesis (e.g., triggering amyloid ß, Tau, or α-synuclein accumulation). In this manuscript, we will review some of the potential common mechanisms involved and evidence in favor and against a role of AD/ADRD in HAND.

Sex differences in neurocognitive screening among adults living with HIV in China.

HIV-infected (HIV+) women may be more vulnerable to neurocognitive impairment (NCI) due to psychological and physiological factors but previous studies show mixed findings. We investigated the neurocognitive performances in HIV+ versus HIV- women and men. This cross-sectional analysis included 669 HIV+ patients (223 women) and 1338 HIV-uninfected (HIV-) controls (446 women) which were frequency matched on sex, education, and 5-year age categories. NCI was screened using the Mini-mental State Examination. Psychomotor speed was assessed using timed alternating hand sequence test. Prevalence of NCI was higher among women versus men in the HIV+ group (16.1% vs 10.5%) but not the HIV- group (4.3% vs 3.5%). HIV+ women performed worse compared to men on psychomotor speed, orientation, attention, and calculation, whereas HIV- women performed worse compared to men on attention and calculation. Adjusted interaction effects of HIV status × sex (women vs men) were significant on orientation, attention, and calculation, and marginally significant on psychomotor speed (p = 0.053). In multivariable models, among both HIV+ women and men, less years of education and depressive symptoms were associated with NCI. Waist-to-hip ratio above the cut-off was strongly associated with NCI among HIV+ women. HIV+ women perform worse on cognitive measures compared to HIV+ men. The association of central obesity with NCI in HIV+ women should be noted.

Association Between Cognitive Tests and Antiretroviral Medication Adherence in Older Adults With HIV.

BACKGROUND: One of the fastest growing populations living with HIV is older adults especially those 65 years of age or older. Current antiretroviral therapy (ART) has prolonged life expectancy of persons with HIV. However, for therapy to be effective, patients need to be adherent. Over time, older persons with HIV may experience HIV-associated neurocognitive disorders or other factors that could affect ART adherence. The use of expedient cognitive tests that help measure medication adherence may be useful for the optimal care of these patients. OBJECTIVE: To investigate the association between cognitive tests and ART adherence. METHODS: This was a prospective study evaluating patients 65 years of age or older with HIV. Cognitive tests used included the Executive Clock-Drawing Task (CLOX) 1 and 2, Trail Making Test parts A and B, and Grooved Pegboard Test (GPB). The medication event monitoring system cap over 1 month was used as the primary measure for adherence. RESULTS: CLOX 1 and GPB were significantly related to adherence ( P < 0.05). Comparison of the magnitude of each measure's relation to adherence suggests that the GPB is a better indicator of ability to adhere ( R = 0.514 vs R = 0.381). Conclusion and Relevance: CLOX 1 and GPB demonstrated an association with adherence in patients 65 years of age or older with HIV. Although the use of these tests to measure adherence in older persons with HIV seems promising, more research is needed to ascertain their ultimate utility.

Modulatory Effects of Nicotine on neuroHIV/neuroAIDS.

Nicotine, one of the key active ingredients in tobacco smoke, exerts its effects via binding to nicotinic acetylcholine receptors (nAChRs). Although both negative and positive pharmacological effects of nicotine have been shown in numerous animals and human studies, its interaction with human immunodeficiency virus-1 (HIV-1) have not been fully elucidated. Even though combined anti-retroviral therapy (cART) limits the progression of HIV-1 to acquired immune deficiency syndrome (AIDS), HIV-associated neurocognitive disorders (HAND) remain prevalent. There is thus a compelling need to enhance our understanding of HAND-related neurologic dysfunction. Some biochemical pathways and physiological dysfunctions have been found to be shared by HAND and Alzheimer's (AD) or Parkinson's (PD) diseases, and nicotine may exert the same neuroprotection in HAND that has been observed in both AD and PD. In the past dozen years, various potential therapeutic effects of nicotine such as neuroprotection have been revealed in both in vivo and in vitro studies, including using HIV-1 transgenic (HIV-1Tg) rat model, which mimics HIV-infected patients receiving cART. In the current review, we describe recent progress in the prevalence of HIV/AIDS with and without cigarette smoking, some animal models for studying neural dysfunction associated with HIV-1 infection, elucidating the modulatory effects of cigarette smoking/nicotine on HIV/AIDS, the anti-inflammatory effects of nicotine, and the neuroprotective effects observed in HIV-1Tg rat model. Taken together, these findings suggest the following: although tobacco smoking does cause deleterious effects in both health and disease conditions such as HIV infection, nicotine, the significant component of tobacco smoke, has been shown to possess some neuroprotective effects in HIV patients, possible via its anti-inflammatory activities. It is therefore necessary to study nicotine's dual effects on neuroHIV/neuroAIDS in hope of better defining the potential medical uses of nicotine or its analogues, and to make them available in a purer and less dangerous form.