Efficiency evaluation of a SARS-CoV-2 diagnostic strategy combining high throughput quantitative antigen immunoassay and real time PCR.

OBJECTIVES: Laboratory testing for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has played an important role in the effort to prevent and contain local outbreaks. The aim of this study was to assess the diagnostic accuracy of a new fully automated SARS-CoV-2 laboratory-based antigen assay (CoV2Ag) and to explore the efficiency of a diagnostic algorithm combining antigen and conventional high-throughput molecular assays to address potential future challenges of the SARS-CoV-2 pandemic. METHODS: One thousand two hundred and twenty four consecutive nasopharyngeal swabs were tested using RT-PCR and CoV2Ag assay. RESULTS: The overall sensitivity and specificity of CoV2Ag were 79.1 and 97.8%, respectively. When the analysis was restricted to cases with Ct values ≤30, the sensitivity of the assay improved to 98.1%. Acceptable sensitivity was found when the analysis was limited to patients presenting within one or two to four days of symptom onset (80.5 and 84.8%, respectively). A retrospective analysis of the use of a two-step diagnostic approach combining the CoV2Ag assay and RT-PCR during an acute pandemic phase of 97 days showed a potential reduction in the number of RT-PCR tests by 36.1%, corresponding to savings in reagent costs and technician workload of approximately €8,000 and 10.5 h per day, respectively. CONCLUSIONS: Our data show that the proposed algorithm represents a valid alternative diagnostic approach to increase testing efficiency during future pandemic phases with high positivity rates (>20%) and elevated numbers of RT-PCR test requests.

Cognitive Phenotypes of HIV Defined Using a Novel Data-driven Approach.

The current study applied data-driven methods to identify and explain novel cognitive phenotypes of HIV. Methods: 388 people with HIV (PWH) with an average age of 46 (15.8) and median plasma CD4+ T-cell count of 555 copies/mL (79% virally suppressed) underwent cognitive testing and 3T neuroimaging. Demographics, HIV disease variables, and health comorbidities were recorded within three months of cognitive testing/neuroimaging. Hierarchical clustering was employed to identify cognitive phenotypes followed by ensemble machine learning to delineate the features that determined membership in the cognitive phenotypes. Hierarchical clustering identified five cognitive phenotypes. Cluster 1 (n=97) was comprised of individuals with normative performance on all cognitive tests. The remaining clusters were defined by impairment on action fluency (Cluster 2; n=46); verbal learning/memory (Cluster 3; n=73); action fluency and verbal learning/memory (Cluster 4; n=56); and action fluency, verbal learning/memory, and tests of executive function (Cluster 5; n=114). HIV detectability was most common in Cluster 5. Machine learning revealed that polysubstance use, race, educational attainment, and volumes of the precuneus, cingulate, nucleus accumbens, and thalamus differentiated membership in the normal vs. impaired clusters. The determinants of persistent cognitive impairment among PWH receiving suppressive treatment are multifactorial nature. Viral replication after ART plays a role in the causal pathway, but psychosocial factors (race inequities, substance use) merit increased attention as critical determinants of cognitive impairment in the context of ART. Results underscore the need for comprehensive person-centered interventions that go beyond adherence to patient care to achieve optimal cognitive health among PWH.

Legacy effect on neuropsychological function in HIV-infected men on combination antiretroviral therapy.

OBJECTIVE: To determine whether combination antiretroviral therapy (cART) initiation alters the trajectory of cognitive performance in HIV+ men, and whether cognition prior to cART predicts postcART function. DESIGN: Longitudinal cohort study. Multicenter AIDS Cohort Study. METHODS: From an initial set of 3701 men with complete neuropsychological data, men with HIV infection were initially matched with men without infection on cognitive status, race, age, and timeline (T0 defined as cART initiation). Propensity score matching was then used to match pairs on depressive symptoms at T0, education, T0 cognitive scores, and recruitment cohort. There were 506 matched pairs of infected and uninfected men in the final analysis. Mixed effect models were constructed to analyze the trajectories of cognitive functions and to test the effect of cART and HIV on cognitive functions over time. RESULTS: Performance in each cognitive domain did not change following the initiation of cART among HIV-infected men with prior impairment and was comparable to the performance of their matched uninfected men. However, among the infected men who were unimpaired prior to cART, motor function declined significantly faster than it did for uninfected controls. CONCLUSIONS: Cognitive dysfunction is persistent in HIV-infected men and cART does not alter the trajectory of cognitive decline in men who were impaired prior to effective therapy. This suggests that current cognitive impairment in HIV+ men results from a legacy effect, and from factors other than the HIV itself. Furthermore, motor skills may be uniquely vulnerable to the virus, cART, or age-related co-morbidities.

Longitudinal 5-year prediction of cognitive impairment among men with HIV disease.

BACKGROUND: Although combination antiretroviral therapy reduced the prevalence of HIV-associated dementia, milder syndromes persist. Our goals were to predict cognitive impairment of the Multicenter AIDS Cohort Study (MACS) participants 5 years ahead and from a large pool of factors, select the ones that mostly contributed to our predictions. DESIGN: Longitudinal, natural and treated history of HIV infection among MSM. METHODS: The MACS is a longitudinal study of the natural and treated history of HIV disease in MSM; the neuropsychological substudy aims to characterize cognitive disorders in men with HIV disease. RESULTS: We modeled on an annual basis the risk of cognitive impairment 5 years in the future. We were able to predict cognitive impairment at individual level with high precision and overperform default methods. We found that while a diagnosis of AIDS is a critical risk factor, HIV infection per se does not necessarily convey additional risk. Other infectious processes, most notably hepatitis B and C, are independently associated with increased risk of impairment. The relative importance of an AIDS diagnosis diminished across calendar time. CONCLUSION: Our prediction models are a powerful tool to help clinicians address dementia in early stages for MACS paticipants. The strongest predictors of future cognitive impairment included the presence of clinical AIDS and hepatitis B or C infection. The fact that the pattern of predictive power differs by calendar year suggests a clinically critical change to the face of the epidemic.

Brain structural correlates of trajectories to cognitive impairment in men with and without HIV disease.

There are distinct trajectories to cognitive impairment among participants in the Multicenter AIDS Cohort Study (MACS). Here we analyzed the relationship between regional brain volumes and the individual trajectories to impairment in a subsample (n = 302) of the cohort. 302 (167 HIV-infected; mean age = 55.7 yrs.; mean education: 16.2 yrs.) of the men enrolled in the MACS MRI study contributed data to this analysis. We used voxel-based morphometry (VBM) to segment the brain images to analyze gray and white matter volume at the voxel-level. A Mixed Membership Trajectory Model had previously identified three distinct profiles, and each study participant had a membership weight for each of these three trajectories. We estimated VBM model parameters for 100 imputations, manually performed the post-hoc contrasts, and pooled the results. We examined the associations between brain volume at the voxel level and the MMTM membership weights for two profiles: one considered "unhealthy" and the other considered "Premature aging." The unhealthy profile was linked to the volume of the posterior cingulate gyrus/precuneus, the inferior frontal cortex, and the insula, whereas the premature aging profile was independently associated with the integrity of a portion of the precuneus. Trajectories to cognitive impairment are the result, in part, of atrophy in cortical regions linked to normal and pathological aging. These data suggest the possibility of predicting cognitive morbidity based on patterns of CNS atrophy.

Cross-sectional analysis of cognitive function using multivariate normative comparisons in men with HIV disease.

BACKGROUND: Prevalence estimates of cognitive impairment in HIV disease vary widely. Here we used multivariate normative comparison (MNC) with identify individuals with impaired cognition, and to compare the results with those using the Frascati and Gisslén criteria. METHODS: The current project used data collected before October 2014 from bisexual/gay men from the Multicenter AIDS Cohort Study. A total of 2904 men (mean age 39.7 years, 52.7% seropositive) had complete data in six cognitive domains at their first neuropsychological evaluation. T-scores were computed for each domain and the MNC was applied to detect impairment among seronegative and seropositive groups. RESULTS: The MNC classified 6.26% of seronegative men as being impaired using a predetermined 5% false discovery rate. By contrast, the Frascati and the Gisslén criteria identified 24.54 and 11.36% of seronegative men as impaired. For seropositive men, the percentage impairment was 7.45, 25.73, and 11.69%, respectively, by the MNC, Frascati and Gisslén criteria. When we used seronegative men without medical comorbidities as the control group, the MNC, the Frascati and the Gisslén criteria identified 5.05, 27.07, and 4.21% of the seronegative men, and 4.34, 30.95, and 4.48% of the seropositive men as having cognitive impairment. For each method, serostatus was not associated with cognitive impairment. CONCLUSION: The MNC controls the false discovery rate and therefore avoids the low specificity that characterizes the Frascati and Gisslén criteria. More research is needed to evaluate the sensitivity of the MNC method in a seropositive population that may be sicker and older than the current study sample and that includes women.

Double dissociation of HIV and substance use disorder effects on neurocognitive tasks dependent on striatal integrity.

OBJECTIVE: Substance use is common among individuals infected with HIV, yet whether neurocognitive effects of HIV can be distinguished from more nonspecific effects of drug dependence and associated comorbidities is not known. DESIGN: Cross-sectional observational study of neurocognitive function among HIV-infected and uninfected individuals with and without substance use disorders (SUDs). METHODS: We compared the performance of 458 (31% HIV-infected) substance-dependent individuals (SDIs) and 90 individuals (23% HIV-infected) with no history of SUDs on measures of delay discounting and probability learning, tasks, which are differentially sensitive to addictive processes and HIV serostatus, respectively. RESULTS: In factorial analyses of covariance adjusted for age, years of education, and sex, we found that SDIs showed significantly higher rates of delay discounting, regardless of HIV serostatus (P < 0.05). Conversely, HIV-infected individuals performed significantly more poorly on probability learning compared with uninfected groups, regardless of SUD history (P < 0.05). CONCLUSION: Theory-driven cognitive neuropsychological tasks may have the capacity to detect neurocognitive effects of HIV not attributable solely to substance use; evidence from functional neuroimaging studies with more selective neurocognitive probes will be critical for hypothesis testing and mapping underlying brain systems more precisely.

Midlife adiposity predicts cognitive decline in the prospective Multicenter AIDS Cohort Study.

OBJECTIVE: Obesity is a common, modifiable cardiovascular and cerebrovascular risk factor. Among people with HIV, obesity may contribute to multisystem dysregulation including cognitive impairment. We examined body mass index (BMI) and central obesity (waist circumference [WC]) in association with domain-specific cognitive function and 10-year cognitive decline in men with HIV infection (MWH) vs HIV-uninfected (HIV-) men. METHODS: A total of 316 MWH and 656 HIV- Multicenter AIDS Cohort Study participants ≥40 years at baseline, with neuropsychological testing every 2 years and concurrent BMI and WC measurements, were included. MWH were included if taking ≥2 antiretroviral agents and had HIV-1 RNA <400 copies/mL at >80% of visits. Mixed-effects models included all visits from 1996 to 2015, stratified by HIV serostatus, and adjusted for sociodemographic, behavioral, and clinical characteristics. At baseline and follow-up, 8% of MWH and 15% of HIV- men and 41% of MWH and 56% of HIV- men were ≥60 years, respectively. RESULTS: Cross-sectionally, higher BMI was inversely associated with motor function in MWH and HIV- men, and attention/working memory in HIV- men. WC was inversely associated with motor function in MWH and HIV- men. Longitudinal associations indicated an obese BMI was associated with a less steep decline in motor function in MWH whereas in HIV- men, obesity was associated with a greater decline in motor function, learning, and memory. WC, or central obesity, showed similar patterns of associations. CONCLUSION: Higher adiposity is associated with lower cognition cross-sectionally and greater cognitive decline, particularly in HIV- men. Overweight and obesity may be important predictors of neurologic outcomes and avenues for prevention and intervention.

Neuropsychological changes in efavirenz switch regimens.

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.

Elevated Depressive Symptoms Are a Stronger Predictor of Executive Dysfunction in HIV-Infected Women Than in Men.

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.

Changes in cognition precede changes in HRQoL among HIV+ males: Longitudinal analysis of the multicenter AIDS cohort study.

OBJECTIVES: Despite treatment-related improvements in morbidity and mortality, HIV-1-infected (HIV+) individuals continue to face a wide range of HIV-associated medical and HIV-associated neurocognitive disorders. Little is known about the impact of cognitive impairment on patients' health-related quality of life (HRQoL). To address this, the current study examined the longitudinal relationship between cognitive functioning and HRQoL among HIV+ individuals. METHOD: The sample consisted of 1,306 HIV+ men enrolled in the Multicenter AIDS Cohort Study. Participants received biannual assessments of cognitive functioning (including tests of processing speed, executive functioning, attention/working memory, motor functioning, learning, and memory) and completed questionnaires assessing HRQoL and depression. Multilevel models were used to examine the longitudinal and cross-lagged relationship between HRQoL and cognition, independent of depression and HIV disease severity. RESULTS: There was a significant relationship between HRQoL and cognitive functioning both between and within subjects. Specifically, individuals who reported better HRQoL reported better cognitive functioning, and longitudinal change in cognition was positively related to change in HRQoL. There was a significant unidirectional-lagged relationship; cognition predicted HRQoL at subsequent visits, but HRQoL did not predict cognitive functioning at subsequent visits. Furthermore, analyses of severity of neurocognitive impairment revealed that transition to a more severe stage of cognitive impairment was associated with a decline in HRQoL. CONCLUSIONS: Overall, the current study suggests that changes in HRQoL are partially driven by changes in cognitive functioning. (PsycINFO Database Record (c) 2019 APA, all rights reserved).

Association of Marijuana Use with Changes in Cognitive Processing Speed and Flexibility for 17 Years in HIV-Seropositive and HIV-Seronegative Men.

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) (ß=-0.41, 95% confidence interval (CI): -0.88, -0.03, p=0.03)] and Symbol Digit Modalities Test (SDMT) (ß= -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) (ß= -0.70, 95% CI: -1.34, -0.05; p=0.03] and cognitive processing speed (SDMT) (ß= -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) (ß= -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.

High Number of Potential Transmitters Revealed in a Population-based Systematic Hepatitis C Virus RNA Screening Among Human Immunodeficiency Virus-infected Men Who Have Sex With Men.

Background: The proportion of undiagnosed hepatitis C virus (HCV) infections in high-risk populations, such as human immunodeficiency virus (HIV)-infected men who have sex with men (MSM) is unclear. Identification of potential HCV transmitters is important to reach World Health Organization HCV elimination targets. Methods: Between October 2015 and May 2016, we performed a systematic HCV RNA-based screening among HIV-infected MSM participating in the Swiss HIV Cohort Study (SHCS). HCV antibodies were measured from all HCV RNA-positive samples. Results: Of 4257 MSM recorded in the SHCS database, we screened 3722 (87%) by HCV polymerase chain reaction, and 177 (4.8%) harbored a replicating HCV infection. We identified 24 individuals (14%) with incident HCV infection; one-third of them had a negative HCV antibody result at the time of HCV RNA positivity. In a multivariable model, elevated liver enzyme values (odds ratio, 14.52; 95% confidence interval, 9.92-21.26), unprotected sex with occasional partners (2.01; 1.36-2.98), intravenous drug use (7.13; 4.36-11.64), noninjectable drug use (1.94; 1.3-2.88), and previous syphilis diagnosis (2.56; 1.74-3.76) were associated with HCV RNA positivity. Conclusions: A systematic HCV RNA-based screening among HIV-infected MSM revealed a high number of potential transmitters. A substantial subpopulation of MSM had incident infection, one-third of whom had a negative HCV antibody test result at the time of the HCV RNA positivity. These data reveal that one-time RNA testing of a high-risk population for HCV RNA might identify more infected persons than routine testing for HCV antibodies and liver enzymes. Clinical Trials Registration: NCT02785666.

Intraindividual variability in neurocognitive performance: No influence due to HIV status or self-reported effort.

INTRODUCTION: HIV-associated neurocognitive disorders (HAND) are estimated to affect approximately 50% of infected individuals at any one time. Dispersion, a type of intraindividual variability in neurocognitive test performance, has been identified as a potential behavioral marker of HAND; however, the specificity of dispersion to HAND and how it is influenced by participant effort when taking neurocognitive tests remain unclear. METHOD: Data were analyzed from 996 (474 HIV-, 522 HIV+) men enrolled in the Multicenter AIDS Cohort Study (MACS). Dispersion was calculated based on the standard deviation of an individual's test scores within a single assessment. Effort was determined using the Visual Analogue Effort Scale. Predictors of dispersion were determined using stepwise linear regression. Dispersion was compared between the HIV serostatus groups using analysis of covariance (ANCOVA), considering demographic and psychosocial variables that differed between the groups. RESULTS: Contrary to our hypothesis, dispersion was not influenced by effort. Instead, poorer neurocognitive ability and race were the sole predictors of dispersion. Dispersion did not differ between the serostatus groups. CONCLUSIONS: Our results indicate that dispersion is a valid indicator of neurocognitive dysfunction that is not due to suboptimal effort; however, it is not specific to HIV and is therefore of limited utility as a behavioral marker of HIV-related neurocognitive impairment.

Differences in Cognitive Function Between Women and Men With HIV.

BACKGROUND: Women may be more vulnerable to HIV-related cognitive dysfunction compared with men because of sociodemographic, lifestyle, mental health, and biological factors. However, studies to date have yielded inconsistent findings on the existence, magnitude, and pattern of sex differences. We examined these issues using longitudinal data from 2 large, prospective, multisite, observational studies of US women and men with and without HIV. SETTING: The Women's Interagency HIV Study (WIHS) and Multicenter AIDS Cohort Study (MACS). METHODS: HIV-infected (HIV+) and uninfected (HIV-) participants in the Women's Interagency HIV Study and Multicenter AIDS Cohort Study completed tests of psychomotor speed, executive function, and fine motor skills. Groups were matched on HIV status, sex, age, education, and black race. Generalized linear mixed models were used to examine group differences on continuous and categorical demographically corrected T-scores. Results were adjusted for other confounding factors. RESULTS: The sample (n = 1420) included 710 women (429 HIV+) and 710 men (429 HIV+) (67% non-Hispanic black; 53% high school or less). For continuous T-scores, sex by HIV serostatus interactions were observed on the Trail Making Test parts A & B, Grooved Pegboard, and Symbol Digit Modalities Test. For these tests, HIV+ women scored lower than HIV+ men, with no sex differences in HIV- individuals. In analyses of categorical scores, particularly the Trail Making Test part A and Grooved Pegboard nondominant, HIV+ women also had a higher odds of impairment compared with HIV+ men. Sex differences were constant over time. CONCLUSIONS: Although sex differences are generally understudied, HIV+ women vs men show cognitive disadvantages. Elucidating the mechanisms underlying these differences is critical for tailoring cognitive interventions.

HIV disease and diabetes interact to affect brain white matter hyperintensities and cognition.

BACKGROUND: Since the onset of combination antiretroviral therapy use, the incidence of HIV-associated dementia and of HIV encephalitis has fallen dramatically. The present study investigates the extent of white matter hyperintensities (WMHs) among individuals with HIV disease, and factors that predict their presence and their impact on psychomotor speed. METHODS: A total of 322 men participating in the Multicenter AIDS Cohort Study (185 HIV-infected, age: 57.5 ±â€Š6.0) underwent MRI scans of the brain. T1-weighted magnetization-prepared rapid gradient-echo (MP-RAGE) and T2-weighted Fluid Attenuated Inversion Recovery (FLAIR) images were obtained and processed using an automated method for identifying and measuring WMHs. WMH burden was expressed as the log10 transformed percentage of total white matter. RESULTS: There were no significant associations between WMHs and HIV disease. However, the extent of WMHs was predicted by age more than 60 (ß = 0.17), non-white race (ß = 0.14), glomerular filtration rate (ß = -0.11), and the presence of diabetes (ß = 0.12). There were no interactions between HIV status and age (ß = -0.03) or between age and diabetes (ß = 0.07). However, the interaction between HIV infection and diabetes was significant (ß = 0.26). The extent of WMHs was significantly associated with performance on measures of psychomotor speed (ß = 0.15). CONCLUSION: In today's therapeutic environment, in HIV-infected and HIV seronegative individuals, those factors which affect the cerebrovasculature are the best predictors of WMHs. Diabetes has a specific impact among HIV-infected, but not uninfected, men, suggesting the need for more aggressive treatment even in the prediabetes state, especially as WMHs affect cognitive functions.

Neuropsychological phenotypes among men with and without HIV disease in the multicenter AIDS cohort study.

OBJECTIVE: Mild forms of HIV-associated neurocognitive disorder (HAND) remain prevalent in the combination antiretroviral therapy (cART) era. This study's objective was to identify neuropsychological subgroups within the Multicenter AIDS Cohort Study (MACS) based on the participant-based latent structure of cognitive function and to identify factors associated with subgroups. DESIGN: The MACS is a four-site longitudinal study of the natural and treated history of HIV disease among gay and bisexual men. METHODS: Using neuropsychological domain scores, we used a cluster variable selection algorithm to identify the optimal subset of domains with cluster information. Latent profile analysis was applied using scores from identified domains. Exploratory and posthoc analyses were conducted to identify factors associated with cluster membership and the drivers of the observed associations. RESULTS: Cluster variable selection identified all domains as containing cluster information except for Working Memory. A three-profile solution produced the best fit for the data. Profile 1 performed below average on all domains, Profile 2 performed average on executive functioning, motor, and speed and below average on learning and memory, Profile 3 performed at or above average across all domains. Several demographic, cognitive, and social factors were associated with profile membership; these associations were driven by differences between Profile 1 and the other profiles. CONCLUSION: There is an identifiable pattern of neuropsychological performance among MACS members determined by all domains except Working Memory. Neither HIV nor HIV-related biomarkers were related with cluster membership, consistent with other findings that cognitive performance patterns do not map directly onto HIV serostatus.

Impact of glycemic status on longitudinal cognitive performance in men with and without HIV infection.

OBJECTIVES: To determine the relationship between glycemic status and cognitive performance in men living with HIV (MLWH) and without HIV infection. DESIGN: A prospective HIV/AIDS cohort study in four US cities between 1999 and 2016. METHODS: Glycemic status was categorized as normal glucose, impaired fasting glucose, controlled diabetes mellitus and uncontrolled diabetes mellitus at each semiannual visit. Cognitive performance was evaluated using nine neuropsychological tests which measure attention, constructional ability, verbal learning, executive functioning, memory and psychomotor speed. Linear mixed models were used to assess the association between glycemic status and cognition. RESULTS: Overall, 900 MLWH and 1149 men without HIV were included. MLWH had significantly more person-visits with impaired fasting glucose (52.1 vs. 47.9%) and controlled diabetes mellitus (58.2 vs. 41.8%) than men without HIV (P < 0.05). Compared with men with normal glucose, men with diabetes mellitus had significantly poorer performance on psychomotor speed, executive function and verbal learning (all P < 0.05). There was no difference in cognition by HIV serostatus. The largest effect was observed in individuals with uncontrolled diabetes mellitus throughout the study period, equivalent to 16.5 and 13.4 years of aging on psychomotor speed and executive function, respectively, the effect of which remained significant after adjusting for HIV-related risk factors. Lower CD4+ nadir was also associated with worse cognitive performance. CONCLUSION: Abnormalities in glucose metabolism were more common among MLWH than men without HIV and were related to impaired cognitive performance. Metabolic status, along with advanced age and previous immunosuppression, may be important predictors of cognition in the modern antiretroviral therapy era.

Verbal and spatial working memory among drug-using HIV-infected men and women.

Working memory (WM) is a critical component of many neurocognitive functions. The literature has demonstrated consistently that WM impairment is more frequent and severe among substance-dependent individuals (SDIs) infected with HIV compared with uninfected SDIs; however, the SDIs who participated in these previous studies were primarily male. There are few published data on WM performance among HIV+ women with or without substance use disorders, and essentially no direct comparisons of WM performance between HIV+ men and women, regardless of substance use. We investigated potential sex and serostatus effects on WM among a sample of 360 SDIs (114 with HIV; 66% female) verified abstinent from alcohol and drugs of abuse at testing and generally comparable on substance use and comorbid characteristics. Participants were tested with the n-back task, a well-established WM measure that is sensitive to HIV-associated cognitive impairment. HIV+ men and women performed spatial and verbal versions of the n-back significantly less accurately compared with HIV- participants. Women showed slower response times compared with men on both versions, regardless of HIV serostatus. Individuals dependent on cocaine showed faster RTs compared with non-dependent users, but this effect was not apparent among opioid- or alcohol-dependent groups. Findings on n-back accuracy are consistent with our previous proposal that WM impairment represents a signature deficit among HIV+ SDIs; however, WM impairment appears less common among HIV+ women without a substance use history. The pattern of sex differences in response speed but serostatus effects on response accuracy is comparable to a recent report by our group of sex differences in learning speed but serostatus effects on delayed recall.

Cognitive trajectories over 4 years among HIV-infected women with optimal viral suppression.

OBJECTIVE: To determine whether persistent viral suppression alters cognitive trajectories among HIV-infected (HIV+) women on combination antiretroviral therapy (cART) by investigating performance longitudinally in uninfected (HIV-) and 3 groups of HIV+ women: those with consistent viral suppression after continuous cART use (VS), those without consistent virologic suppression despite continuous cART use (NVS), and those without consistent virologic suppression after intermittent cART use (Int NVS). METHODS: Two hundred thirty-nine VS, 220 NVS, 172 Int NVS, and 301 HIV- women from the Women's Interagency HIV Study (WIHS) completed neuropsychological testing every 2 years for 3 visits between 2009 and 2013. Mixed-effects regressions were used to examine group differences on continuous T scores and categorical measures of impairment (T score <40). RESULTS: On global function, VS women demonstrated lower scores and were more likely to score in the impaired range than HIV- women (p = 0.01). These differences persisted over time (group × time, p > 0.39). VS women demonstrated lower learning and memory scores than HIV- women (p < 0.05) and lower attention/working memory and fluency scores than HIV- and NVS women (p < 0.05). Group differences in scores persisted over time. Categorically, VS women were more likely to be impaired on attention/working memory and executive function than HIV- women (p < 0.05). On motor skills, VS and NVS women showed a greater decline and were more likely to be impaired than HIV- women (p < 0.05). CONCLUSIONS: Cognitive difficulties remain among HIV+ women despite persistent viral suppression. In some instances, VS women are worse than NVS women, reinforcing the need for novel adjunctive therapies to attenuate cognitive problems.