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.

Imaging of Brain Structural and Functional Effects in People With Human Immunodeficiency Virus.

Before the introduction of antiretroviral therapy, human immunodeficiency virus (HIV) infection was often accompanied by central nervous system (CNS) opportunistic infections and HIV encephalopathy marked by profound structural and functional alterations detectable with neuroimaging. Treatment with antiretroviral therapy nearly eliminated CNS opportunistic infections, while neuropsychiatric impairment and peripheral nerve and organ damage have persisted among virally suppressed people with HIV (PWH), suggesting ongoing brain injury. Neuroimaging research must use methods sensitive for detecting subtle HIV-associated brain structural and functional abnormalities, while allowing for adjustments for potential confounders, such as age, sex, substance use, hepatitis C coinfection, cardiovascular risk, and others. Here, we review existing and emerging neuroimaging tools that demonstrated promise in detecting markers of HIV-associated brain pathology and explore strategies to study the impact of potential confounding factors on these brain measures. We emphasize neuroimaging approaches that may be used in parallel to gather complementary information, allowing efficient detection and interpretation of altered brain structure and function associated with suboptimal clinical outcomes among virally suppressed PWH. We examine the advantages of each imaging modality and systematic approaches in study design and analysis. We also consider advantages of combining experimental and statistical control techniques to improve sensitivity and specificity of biotype identification and explore the costs and benefits of aggregating data from multiple studies to achieve larger sample sizes, enabling use of emerging methods for combining and analyzing large, multifaceted data sets. Many of the topics addressed in this article were discussed at the National Institute of Mental Health meeting "Biotypes of CNS Complications in People Living with HIV," held in October 2021, and are part of ongoing research initiatives to define the role of neuroimaging in emerging alternative approaches to identifying biotypes of CNS complications in PWH. An outcome of these considerations may be the development of a common neuroimaging protocol available for researchers to use in future studies examining neurological changes in the brains of PWH.

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.

Experiences With Smoking Cessation Attempts and Prior Use of Cessation Aids in Smokers With HIV: Findings From a Focus Group Study Conducted in Durham, North Carolina.

Cigarette smoking remains disproportionately prevalent and is increasingly a cause of death and disability among people with HIV (PWH). Many PWH are interested in quitting, but interest in and uptake of first-line smoking cessation pharmacotherapies are varied in this population. To provide current data regarding experiences with and perceptions of smoking cessation and cessation aids among PWH living in Durham, North Carolina, the authors conducted five focus group interviews (total n = 24; 96% African American) using semistructured interviews. Interviews were recorded, transcribed, coded, and thematically analyzed. Major themes included ambivalence and/or lack of interest in cessation; presence of cessation barriers; perceived perceptions of ineffectiveness of cessation aids; perceived medication side effects; and conflation of the harms resulting from use of tobacco products and nicotine replacement therapy. Innovative and effective interventions must account for the aforementioned multiple barriers to cessation as well as prior experiences with and misperceptions regarding cessation aids.

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.

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.

Cigarette Smoking and Cessation-Related Interactions With Health Care Providers in the Context of Living With HIV: Focus Group Study Findings.

ABSTRACT: Smoking is disproportionately prevalent among people living with HIV (PLWH) compared with the general population. We conducted five focus groups (n = 24) using semi-structured interview guides to explore perceptions and experiences of smoking and cessation-related interactions with health care providers among smokers with HIV. Major themes included a limited understanding of how smoking affects illness among PLWH and minimal discussion about cessation with providers. Findings highlight the need to educate smokers with HIV about the known impacts of smoking on illness among PLWH and to facilitate greater discussion of cessation between providers and smokers with HIV. Prior experiences with smoking cessation medications and desire for additional information regarding these medications should be considered when implementing medication regimens in research and clinical settings.

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.

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.

HIV Risk Behavior Among Methamphetamine Users Entering Substance Abuse Treatment in Cape Town, South Africa.

South Africa is experiencing a growing methamphetamine problem, and there is concern that methamphetamine use may accelerate HIV transmission. There has been little research on the HIV prevention needs of methamphetamine users receiving substance abuse treatment in South Africa. This study assessed the prevalence and correlates of HIV risk behaviors among 269 methamphetamine users entering substance abuse treatment in two clinics in Cape Town. The prevalence of sexual risk behaviors was high among sexually active participants: 34 % multiple partners, 26 % unprotected intercourse with a casual partner, and 24 % sex trading for money/methamphetamine. The strongest predictor of all sexual risk behaviors was concurrent other drug use. Over half had not been HIV tested in the past year, and 25 % had never been tested, although attitudes toward HIV testing were overwhelmingly positive. This population of primarily heterosexual, non-injecting methamphetamine users is a high-risk group in need of targeted HIV prevention interventions. Substance abuse treatment is an ideal setting in which to reach methamphetamine users for HIV services.

HIV testing and sero-prevalence among methamphetamine users seeking substance abuse treatment in Cape Town.

INTRODUCTION AND AIMS: Methamphetamine use is highly prevalent in parts of South Africa, and there is concern this will contribute to the country's substantial HIV epidemic. We examined the feasibility of implementing routine HIV testing at a community-based substance abuse treatment centre in Cape Town and determined the HIV sero-prevalence among methamphetamine users seeking treatment at this site. DESIGN AND METHODS: In this cross-sectional study, 293 participants completed measures of demographics, substance use and HIV treatment. HIV sero-prevalence was determined by a rapid finger-prick HIV test, and prior HIV diagnosis was confirmed via clinic records. RESULTS: The majority of participants were male and self-identified as 'Coloured', with a mean age of 28 years. The HIV sero-prevalence was 3.8%. Of the 11 participants who tested HIV positive, four were newly diagnosed. HIV-positive and HIV-negative participants were comparable on demographic and substance use factors. Uptake of HIV testing among all clients at the drug treatment centre increased from <5% prior to study initiation to 89% after study completion. Measures implemented to ensure high rates of HIV testing were regarded as sustainable. DISCUSSION AND CONCLUSIONS: Our study suggests that integrating routine HIV testing into substance abuse treatment is feasible in a community-based health centre. The low HIV prevalence among this sample of treatment-seeking methamphetamine users highlights the potential benefits of supporting expanded efforts to optimise HIV prevention with this young adult population. [Gouse H, Joska JA, Lion RR, Watt MH, Burnhams W, Carrico AW, Meade CS. HIV testing and sero-prevalence among methamphetamine users seeking substance abuse treatment in Cape Town. Drug Alcohol Rev 2016;35:580-583].

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.

Risk patterns preceding diagnosis among newly HIV-diagnosed men who have sex with men in New York City.

Men who have sex with men (MSM) are at high risk for contracting and transmitting HIV. They are increasingly encouraged to get tested, but understanding of the interplay between HIV testing and risk behavior is limited. One hundred fifty newly HIV-diagnosed (within past 3 months) MSM were recruited from a community clinic in New York City. Participants completed an interview assessing sexual behavior and substance use during the 3 months pre-diagnosis, current depressive symptoms, and prior HIV testing. HIV-related health characteristics at diagnosis were abstracted from medical records. Analyses examined factors associated with unprotected anal intercourse (UAI) in the 3 months pre-diagnosis, and with a negative HIV test in the 12 months pre-diagnosis. The sample was young (mean age=32.5, SD=8.8), ethnically diverse (62% racial/ethnic minority), low-income (71%≤$30,000/year), and educated (48% college/advanced degree). Most (95%) had a prior negative HIV test, 55% within the last 12 months. Significant risk behavior was reported, with 79% reporting UAI. UAI was associated with recent testing and use of substances during sexual behavior. Recent testing was associated with being employed/a student, having had UAI, and higher CD4 count. Implications for future research addressing perceived HIV risk, HIV testing utilization, and risk behavior are discussed.

HIV risk behavior in opioid dependent adults seeking detoxification treatment: an exploratory comparison of heroin and oxycodone users.

Heroin users are at high risk for HIV infection, but little is known about HIV risk in oxycodone users. This study examined HIV risk behaviors in heroin (n = 27) and oxycodone (n = 23) users seeking inpatient detoxification at a private psychiatric hospital. Drug use histories were similar, except oxycodone users used marijuana more frequently. Injection drug risk occurred exclusively among heroin users. The rates of sexual activity (66%), unprotected intercourse (69%), sex while intoxicated (74%), and sex with strangers (24%) were similar, but more oxycodone users had multiple partners (39% vs. 6%, p < .05). HIV prevention efforts should target both heroin and oxycodone users.

A randomized controlled trial of a coping group intervention for adults with HIV who are AIDS bereaved: longitudinal effects on grief.

The authors sought to study the longitudinal effects of a cognitive-behavioral group intervention for coping with AIDS bereavement among a diverse sample of adults who were HIV positive. Participants (N = 267) were randomly assigned to receive the 12-week intervention or individual therapy upon request. Measures were administered at baseline, postintervention, and 4-, 8-, and 12-month follow-ups. Longitudinal data were analyzed with linear mixed models to examine change in grief by condition across the study period and the effect of the intervention on grief through its interaction with psychiatric distress. The authors used the Grief Reaction Index to assess grief and the Symptom Checklist-90-Revised to assess global psychiatric distress. Participants in both conditions reported decreases in grief severity. However, among those with higher levels of psychiatric distress, participants in the group intervention had significantly lower grief severity scores compared with participants in the individual therapy condition. The long-term effectiveness of this AIDS-bereavement intervention for psychiatrically distressed people with HIV/AIDS supports the need for tailored interventions among those at risk for complicated grief responses.