HIV viremia contributes to neurocognitive impairments in persons who use cocaine.

Persons with HIV (PWH) who use illicit drugs are at elevated risk for neurocognitive impairment (NCI). This study investigated the effects of HIV disease and HIV viremia on NCI among adults who use cocaine. PWH who were not virologically suppressed showed greater global deficits compared to participants with HIV viral suppression and HIV-negative participants, but no differences emerged between the latter two groups. These findings highlight the adverse effects of poorly controlled HIV disease on NCI, beyond the independent effects of cocaine on cognition, and underscore the importance of strengthening the HIV care continuum for persons who use cocaine.

Neuroimaging and immunological features of neurocognitive function related to substance use in people with HIV.

This study sought to identify neuroimaging and immunological factors associated with substance use and that contribute to neurocognitive impairment (NCI) in people with HIV (PWH). We performed cross-sectional immunological phenotyping, neuroimaging, and neurocognitive testing on virally suppressed PWH in four substance groups: cocaine only users (COC), marijuana only users (MJ), dual users (Dual), and Non-users. Participants completed substance use assessments, multimodal MRI brain scan, neuropsychological testing, and blood and CSF sampling. We employed a two-stage analysis of 305 possible biomarkers of cognitive function associated with substance use. Feature reduction (Kruskal Wallis p-value < 0.05) identified 53 biomarkers associated with substance use (22 MRI and 31 immunological) for model inclusion along with clinical and demographic variables. We employed eXtreme Gradient Boosting (XGBoost) with these markers to predict cognitive function (global T-score). SHapley Additive exPlanations (SHAP) values were calculated to rank features for impact on model output and NCI. Participants were 110 PWH with sustained HIV viral suppression (33 MJ, 12 COC, 22 Dual, and 43 Non-users). The ten highest ranking biomarkers for predicting global T-score were 4 neuroimaging biomarkers including functional connectivity, gray matter volume, and white matter integrity; 5 soluble biomarkers (plasma glycine, alanine, lyso-phosphatidylcholine (lysoPC) aC17.0, hydroxy-sphingomyelin (SM.OH) C14.1, and phosphatidylcholinediacyl (PC aa) C28.1); and 1 clinical variable (nadir CD4 count). The results of our machine learning model suggest that substance use may indirectly contribute to NCI in PWH through both metabolomic and neuropathological mechanisms.

Hypoactivation in the precuneus and posterior cingulate cortex during ambiguous decision making in individuals with HIV.

People with human immunodeficiency virus (HIV) often have neurocognitive impairment. People with HIV make riskier decisions when the outcome probabilities are known, and have abnormal neural architecture underlying risky decision making. However, ambiguous decision making, when the outcome probabilities are unknown, is more common in daily life, but the neural architecture underlying ambiguous decision making in people with HIV is unknown. Eighteen people with HIV and 20 controls completed a decision making task while undergoing functional magnetic resonance imaging scanning. Participants chose between a certain reward and uncertain reward with a known (risky) or unknown (ambiguous) probability of winning. There were three levels of risk: high, medium, and low. Ambiguous > risky brain activity was compared between groups. Ambiguous > risky brain activity was correlated with emotional/psychiatric functioning in people with HIV. Both groups were similarly ambiguity-averse. People with HIV were more risk-averse than controls and chose the high-risk uncertain option less often. People with HIV had hypoactivity in the precuneus, posterior cingulate cortex (PCC), and fusiform gyrus during ambiguous > medium risk decision making. Ambiguous > medium risk brain activity was negatively correlated with emotional/psychiatric functioning in individuals with HIV. To make ambiguous decisions, people with HIV underrecruit key regions of the default mode network, which are thought to integrate internally and externally derived information to come to a decision. These regions and related cognitive processes may be candidates for interventions to improve decision-making outcomes in people with HIV.

Machine learning prediction of neurocognitive impairment among people with HIV using clinical and multimodal magnetic resonance imaging data.

Diagnosis of HIV-associated neurocognitive impairment (NCI) continues to be a clinical challenge. The purpose of this study was to develop a prediction model for NCI among people with HIV using clinical- and magnetic resonance imaging (MRI)-derived features. The sample included 101 adults with chronic HIV disease. NCI was determined using a standardized neuropsychological testing battery comprised of seven domains. MRI features included gray matter volume from high-resolution anatomical scans and white matter integrity from diffusion-weighted imaging. Clinical features included demographics, substance use, and routine laboratory tests. Least Absolute Shrinkage and Selection Operator Logistic regression was used to perform variable selection on MRI features. These features were subsequently used to train a support vector machine (SVM) to predict NCI. Three different classification tasks were performed: one used only clinical features; a second used only selected MRI features; a third used both clinical and selected MRI features. Model performance was evaluated by area under the receiver operating characteristic curve (AUC), accuracy, sensitivity, and specificity with a tenfold cross-validation. The SVM classifier that combined selected MRI with clinical features outperformed the model using clinical features or MRI features alone (AUC: 0.83 vs. 0.62 vs. 0.79; accuracy: 0.80 vs. 0.65 vs. 0.72; sensitivity: 0.86 vs. 0.85 vs. 0.86; specificity: 0.71 vs. 0.37 vs. 0.52). Our results provide preliminary evidence that combining clinical and MRI features can increase accuracy in predicting NCI and could be developed as a potential tool for NCI diagnosis in HIV clinical practice.

Web-Based Cognitive Training to Improve Working Memory in Persons with Co-Occurring HIV Infection and Cocaine Use Disorder: Outcomes from a Randomized Controlled Trial.

Neurocognitive impairment (NCI) remains a persistent complication of HIV disease that nearly half of persons with HIV experience, and rates are even higher in persons who use substances such as cocaine. Cognitive training is a promising intervention for HIV-associated NCI. In this randomized controlled trial, we examined the feasibility and effectiveness of a web-based cognitive training program to improve working memory in a sample of 58 persons with HIV and cocaine use disorder. Participants were randomly assigned to either the experimental working memory training arm or the attention control training arm and completed up to 48 daily sessions over 10 weeks. Overall, treatment completion (74%) and retention rates (97%) were high, and participant feedback indicated the intervention was acceptable. Our results show that the intervention successfully reduced working memory deficits in the experimental arm relative to the control arm. Our findings support both the feasibility and effectiveness of cognitive training in this population.

Structural and Functional Brain Abnormalities in Human Immunodeficiency Virus Disease Revealed by Multimodal Magnetic Resonance Imaging Fusion: Association With Cognitive Function.

BACKGROUND: Human immunodeficiency virus (HIV)-associated neurocognitive impairment remains a prevalent comorbidity that impacts daily functioning and increases morbidity. While HIV infection is known to cause widespread disruptions in the brain, different magnetic resonance imaging (MRI) modalities have not been effectively integrated. In this study, we applied 3-way supervised fusion to investigate how structural and functional coalterations affect cognitive function. METHODS: Participants (59 people living with HIV and 58 without HIV) completed comprehensive neuropsychological testing and multimodal MRI scanning to acquire high-resolution anatomical, diffusion-weighted, and resting-state functional images. Preprocessed data were reduced using voxel-based morphometry, probabilistic tractography, and regional homogeneity, respectively. We applied multimodal canonical correlation analysis with reference plus joint independent component analysis using global cognitive functioning as the reference. RESULTS: Compared with controls, participants living with HIV had lower global cognitive functioning. One joint component was both group discriminating and correlated with cognitive function. This component included the following covarying regions: fractional anisotropy in the corpus callosum, short and long association fiber tracts, and corticopontine fibers; gray matter volume in the thalamus, prefrontal cortex, precuneus, posterior parietal regions, and occipital lobe; and functional connectivity in frontoparietal and visual processing regions. Component loadings for fractional anisotropy also correlated with immunosuppression. CONCLUSIONS: These results suggest that coalterations in brain structure and function can distinguish people with and without HIV and may drive cognitive impairment. As MRI becomes more commonplace in HIV care, multimodal fusion may provide neural biomarkers to support diagnosis and treatment of cognitive impairment.

Frequency of Cannabis Use and Medical Cannabis Use Among Persons Living With HIV in the United States: Findings From a Nationally Representative Sample.

Little is known about cannabis use frequency, medical cannabis use, or correlates of use among persons living with HIV (PLWH) in United States nationally representative samples. Data came from 626 PLWH from the 2005-2015 National Survey on Drug Use and Health. Logistic regression identified characteristics associated with frequency of cannabis use. Chi-squares identified characteristics associated with medial cannabis use. Non-daily and daily cannabis use was reported by 26.9% and 8.0%. Greater perceived risk of cannabis use was negatively associated with daily and non-daily use. Younger age, substance use, and binge drinking were positively associated with non-daily cannabis use. Smoking and depression were associated with non-daily and daily use. One-quarter reported medical cannabis use. Medical users were more likely to be White, married, and nondrinkers. Cannabis use was common among PLWH. Findings help to differentiate between cannabis users based on frequency of use and medical versus recreational use.

Memory Impairment in HIV-Infected Individuals with Early and Late Initiation of Regular Marijuana Use.

Marijuana use is disproportionately prevalent among HIV-infected individuals. The strongest neurocognitive effect of marijuana use is impairment in the domain of memory. Memory impairment is also high among HIV-infected persons. The present study examined 69 HIV-infected individuals who were stratified by age of regular marijuana initiation to investigate how marijuana use impacts neurocognitive functioning. A comprehensive battery assessed substance use and neurocognitive functioning. Findings indicated early onset marijuana users (regular use prior to age 18), compared to non-marijuana users and late onset marijuana users (regular use at age 18 or later), were over 8 times more likely to have learning impairment and nearly 4 times more likely to have memory impairment. A similar pattern of early onset marijuana users performing worse in learning emerged when examining domain deficit scores. The potential for early onset of regular marijuana use to exacerbate already high levels of memory impairment among HIV-infected persons has important clinical implications, including increased potential for medication non-adherence and difficulty with independent living.

Cocaine dependence modulates the effect of HIV infection on brain activation during intertemporal decision making.

BACKGROUND: Both HIV infection and chronic cocaine use alter the neural circuitry of decision making, but the interactive effects of these commonly comorbid conditions have not been adequately examined. This study tested how cocaine moderates HIV-related neural activation during an intertemporal decision-making task. METHODS: The sample included 73 participants who differed on cocaine and HIV status (18 COC+/HIV+, 19 COC+/HIV-, 19 COC-/HIV+, 17 COC-/HIV-). Participants made choices between smaller, sooner and larger, delayed rewards while undergoing functional MRI. Choices varied in difficulty based on subjective value: hard (equivalently valued), easy (disparately valued), and control choices. A mixed-effects model controlling for education and smoking identified main and interactive effects of HIV and COC during hard relative to easy choices (difficulty contrast). RESULTS: COC+ status was associated with lower activation in bilateral frontal gyri and right insular and posterior parietal cortices. HIV+ status was associated with higher activation in the visual cortex, but lower activation in bilateral prefrontal cortices and cerebellum and left posterior parietal cortex. COC moderated the effects of HIV in several clusters centered in the bilateral prefrontal cortices and cerebellum. In post-hoc analyses, there were significant effects of HIV status on activation for COC+, but not COC-, participants; interaction effects remained after controlling for polysubstance use. CONCLUSION: Cocaine use may diminish the compensatory neural activation often seen among HIV+ samples during decision making. Our results highlight the importance of examining the neuropsychiatric effects of comorbid medical conditions to identify potential neural targets for cognitive remediation interventions.

Addiction and treatment experiences among active methamphetamine users recruited from a township community in Cape Town, South Africa: A mixed-methods study.

BACKGROUND: Since 2000, there has been a dramatic increase in methamphetamine use in South Africa, but little is known about the experiences of out-of-treatment users. This mixed-methods study describes the substance use histories, addiction symptoms, and treatment experiences of a community-recruited sample of methamphetamine users in Cape Town. METHODS: Using respondent driven sampling, 360 methamphetamine users (44% female) completed structured clinical interviews to assess substance abuse and treatment history and computerized surveys to assess drug-related risks. A sub-sample of 30 participants completed in-depth interviews to qualitatively explore experiences with methamphetamine use and drug treatment. RESULTS: Participants had used methamphetamine for an average of 7.06 years (SD=3.64). They reported using methamphetamine on an average of 23.49 of the past 30 days (SD=8.90); 60% used daily. The majority (90%) met ICD-10 criteria for dependence, and many reported severe social, financial, and legal consequences. While only 10% had ever received drug treatment, 90% reported that they wanted treatment. In the qualitative interviews, participants reported multiple barriers to treatment, including beliefs that treatment is ineffective and relapse is inevitable in their social context. They also identified important motivators, including desires to be drug free and improve family functioning. CONCLUSION: This study yields valuable information to more effectively respond to emerging methamphetamine epidemics in South Africa and other low- and middle-income countries. Interventions to increase uptake of evidence-based services must actively seek out drug users and build motivation for treatment, and offer continuing care services to prevent relapse. Community education campaigns are also needed.

HIV testing behaviors and attitudes among community recruited methamphetamine users in a South African township.

Methamphetamine users in South Africa are at high risk for HIV infection and transmission, but little is known about HIV testing in this population. We examined HIV testing behaviors and attitudes in 362 methamphetamine users recruited using chain referral sampling from one peri-urban community. Many (44 %) had not been HIV tested in the past year. HIV testing was associated with positive testing attitudes, less AIDS stigma, and greater methamphetamine stigma. Among participants who reported HIV infection (8 %), less than half were linked to care. Findings highlight the need to identify barriers to HIV service uptake for methamphetamine users.

Motives for cannabis use in high-risk adolescent users.

The present investigation examined the relationships between motives for cannabis use and negative consequences associated with cannabis use following a brief intervention. The sample consisted of 205 adolescent cannabis users (66.3% male), who were recruited in high schools and randomly assigned to a brief two-session motivational enhancement therapy (MET) or an educational feedback control (EFC). Results supported the hypothesis that using cannabis to cope with negative affect would predict the number of problems and dependence symptoms related to cannabis use, after controlling for age, gender, years and frequency of cannabis use, and internalizing and externalizing behavior problems. Significant interactions between internalizing behavior problems and the coping motive showed that using to cope was associated with a higher number of cannabis dependence symptoms among adolescents reporting lower levels internalizing behavior problems. Findings support the potential utility of conducting further research to explore the coping motive as an important indicator of problematic cannabis use.