HIV Immunocapture Reveals Particles Expressed in Semen under INSTI-based Therapy are Largely Myeloid Cell-Derived and Disparate from Circulating Provirus.

As use of HIV integrase strand transfer inhibitors (INSTI) increases and formulations are being developed for maintenance therapies and chemoprophylaxis, assessing virus suppression under INSTI-based regimens in prevention-relevant biologic compartments, such as the male genital tract, is timely. We used cell-source marker virion immunocapture to examine amplification of particle RNA then assessed the phylogenetic relatedness of seminal and blood viral sequences from men with HIV who were prescribed INSTI-based regimens. Seminal plasma immunocaptures yielded amplifiable virion RNA from 13/24 (54%) men, and the sequences were primarily associated with markers indicative of macrophage and resident dendritic cell sources. Genetic distances were greatest (>2%) between seminal virions and circulating proviruses, pointing to ongoing low-level expression from tissue-resident cells. While the low levels in semen predict an improbable likelihood of transmission, viruses with large genetic distances are expressed under potent INSTI therapy and have implications for determining epidemiologic linkages if adherence is suboptimal.

The association of depression and anxiety symptoms to three different types of activities of daily living in persons with and without HIV.

Mood disorders are highly prevalent in people living with HIV (PLWH) and represent a potential contributor to functional impairment in activities of daily living. We aimed to determine if (1) Anxiety and depression symptoms were independently associated with impairments in basic self-care, role functioning, and social functioning and (2) PLWH differentially experienced impairments due to mood symptoms compared to those without HIV. Data for this study were obtained from 150 individuals (87 PLWH, 61% male, mean age = 44) via a cross-sectional study on alcohol and HIV-associated brain dysfunction. The Beck Anxiety Inventory (BAI) and the Center for Epidemiologic Studies Depression Scale (CES-D) were used to assess anxiety and depressive symptoms. Higher anxiety symptoms were associated with role functioning impairment, while higher depressive and anxiety symptoms were each associated with social functioning impairment. As depressive symptoms increased, PLWH were 3x more likely to have impairments in role functioning compared to those without HIV. HIV status did not interact with mood symptoms to affect basic self-care or social functioning. Overall, mood symptoms are associated with different types of functional impairment, and improved management of mood symptoms could lead to improved role and social functioning.

Integrating Alcohol Biosensors With Ecological Momentary Intervention (EMI) for Alcohol Use: a Synthesis of the Latest Literature and Directions for Future Research.

Purpose of Review: Excessive alcohol use is a major public health concern. With increasing access to mobile technology, novel mHealth approaches for alcohol misuse, such as ecological momentary intervention (EMI), can be implemented widely to deliver treatment content in real time to diverse populations. This review summarizes the state of research in this area with an emphasis on the potential role of wearable alcohol biosensors in future EMI/just-in-time adaptive interventions (JITAI) for alcohol use. Recent Findings: JITAI emerged as an intervention design to optimize the delivery of EMI for various health behaviors including substance use. Alcohol biosensors present an opportunity to augment JITAI/EMI for alcohol use with objective information on drinking behavior captured passively and continuously in participants' daily lives, but no prior published studies have incorporated wearable alcohol biosensors into JITAI for alcohol-related problems. Several methodological advances are needed to accomplish this goal and advance the field. Future research should focus on developing standardized data processing, analysis, and interpretation methods for wrist-worn biosensor data. Machine learning algorithms could be used to identify risk factors (e.g., stress, craving, physical locations) for high-risk drinking and develop decision rules for interpreting biosensor-derived transdermal alcohol concentration (TAC) data. Finally, advanced trial design such as micro-randomized trials (MRT) could facilitate the development of biosensor-augmented JITAI. Summary: Wrist-worn alcohol biosensors are a promising potential addition to improve mHealth and JITAI for alcohol use. Additional research is needed to improve biosensor data analysis and interpretation, build new machine learning models to facilitate integration of alcohol biosensors into novel intervention strategies, and test and refine biosensor-augmented JITAI using advanced trial design.

Association between cannabis use disorder and greater apathy in adults with HIV.

BACKGROUND: Apathy is prevalent among people with HIV (PWH) and is associated with poor clinical outcomes. Cannabis use and Cannabis Use Disorder (CUD) are also disproportionately prevalent among PWH. CUD and younger onset of cannabis use may be linked to apathy in the general population; however, patterns of use most strongly associated with apathy have not been firmly established, and it is unclear whether cannabis use is linked to apathy in PWH. METHODS: We examined associations in 311 adult PWH between Apathy Evaluation Scale-Self (AES-S) scores and CUD history (current/past/no CUD/no cannabis use) and between AES-S scores and age of CUD onset (adolescent-onset/adult-onset). We also examined robustness of associations to adjustment for depressive symptoms (which may overlap with apathy symptoms) and alcohol use. RESULTS: Current CUD was associated with greater AES-S scores relative to cannabis users with no CUD history (ß = 2.13, 95 % CI = 0.37-3.90, p = 0.018). Adolescent-onset CUD was not associated with greater apathy relative to adult-onset CUD (ß = 0.56, 95 % CI = -2.57 - 3.68, p = 0.7). Associations became nonsignificant after adjustment for depressive symptoms, but not after adjustment for alcohol use. Alcohol use was correlated with apathy (r = 0.19, 95 % CI: 0.076-0.29, p = 0.001). CONCLUSIONS: Cannabis Use Disorder and at-risk alcohol use are associated with apathy among PWH; this finding highlights the need for substance use disorder prevention and treatment among PWH.

Resting state connectivity in people living with HIV before and after stopping heavy drinking.

Background: Heavy alcohol use in people living with HIV (PLWH) has widespread negative effects on neural functioning. It remains unclear whether experimentally-induced reduction in alcohol use could reverse these effects. We sought to determine the effects of 30-days drinking cessation/reduction on resting state functional connectivity in people with and without HIV. Methods: Thirty-five participants (48.6% PLWH) demonstrating heavy alcohol use attempted to stop drinking for 30 days via contingency management (CM). MRI was acquired at baseline and after thirty days, and functional connectivity across five resting-state fMRI (rsfMRI) networks was calculated with the Conn toolbox for Matlab and examined in relation to transdermal alcohol concentration (TAC) recorded by the ankle-worn secure continuous remote alcohol monitor (SCRAM) and self-reported alcohol use (timeline follow-back; TLFB). Associations between alcohol use and reduction, HIV status, functional connectivity, and change in functional connectivity across five major rsfMRI networks were determined relative to the pre- and post-CM timepoints. Results: Baseline resting-state functional connectivity was not significantly associated with average TAC-AUC during the pre-CM period, though higher self-reported alcohol use over the preceding 30 days was significantly associated with higher baseline connectivity within the Dorsal Attention Network (DAN; p-FDR < 0.05). Baseline connectivity within the Salience network was significantly negatively related to objective drinking reduction after intervention (DAN; p-FDR < 0.05), whereas baseline connectivity within the Limbic network was positively associated with self-reported drinking reduction (p-FDR < 0.05). Change in between-networks functional connectivity after intervention was significantly positively associated with biosensor-confirmed drinking reduction such that higher reduction was associated with stronger connectivity between the limbic and fronto-parietal control networks (p-FDR < 0.05). PLWH with lower DAN connectivity at baseline demonstrated poorer alcohol reduction than those with higher DAN connectivity at baseline. Discussion: Lower resting-state functional connectivity of the Salience network significantly predicted stronger drinking reduction across all participants, suggesting a potential biomarker for reduced susceptibility to the environmental and social cues that often make alcohol use reduction attempts unsuccessful. Increased between-networks connectivity was observed in participants with higher alcohol reduction after CM, suggesting a positive benefit to brain connectivity associated with reduced drinking. PLWH with lower baseline DAN connectivity may not benefit as greatly from CM for alcohol reduction.