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Hepatitis C virus (HCV) and injection drug use among young women are dramatically rising in the rural United States. From 2004 to 2017, heroin use among non-pregnant women increased 22.4% biennially, mirroring increases in HCV cases, especially among younger populations. Young women who inject drugs (YWID, ages 18-35) face elevated HCV risk due to biological, behavioral, and socio-cultural factors. Barriers to HCV testing and treatment services further delay diagnoses, fuel transmission, and limit access to harm reduction services. This study applies the Theoretical Domains Framework (TDF) to identify factors influencing HCV testing and treatment among YWID in rural Appalachia Ohio. We conducted in-depth interviews with YWID (n = 30) in 2023 to understand their HCV testing and treatment experiences in rural Appalachia Ohio. Interviews were transcribed, inductively coded, and analyzed using grounded theory. Identified themes were mapped onto the TDF domains. Key TDF domains influencing HCV care included knowledge, beliefs about consequences, and intentions. While YWID knew where to get tested, they expressed uncertainty about treatment value and access while actively using drugs. Social influences, stigma, and mistreatment by healthcare providers created barriers to treatment. Environmental context and resources, such as transportation, also influenced access to care. YWID in rural Appalachia face barriers to HCV care, such as gaps in knowledge about HCV treatment, which is compounded by gendered stigma, and logistical challenges. Rapidly changing treatment restrictions led to misinformation about treatment access. These gaps highlight the need for interventions specifically designed to address YWID lived experiences.

Background People who inject drugs (PWID) are at risk for HIV and opioid overdose. We piloted PARTNER UP, a telemedicine-based program to provide PWID with access to both oral pre-exposure prophylaxis (PrEP) for HIV prevention and medication for opioid use disorder (MOUD) through two syringe services programs (SSPs) in North Carolina. We conducted a qualitative evaluation to assess the acceptability and feasibility of PARTNER UP from the participant perspective. Methods PARTNER UP participants met with a provider for an initial in-person visit at the SSP, followed by weekly telemedicine visits in month 1 and then monthly telemedicine visits until program end at month 6. Using a qualitative descriptive study design, we conducted in-depth interviews with a subsample of PARTNER UP participants at 1 month and 4 months. Informed by the technology acceptance model, we assessed participant perceptions of the usefulness and ease of use of PARTNER UP, as well as their intent to continue to use the program’s components. We audio-recorded all interviews with participants’ permission and used applied thematic analysis to analyze the verbatim transcripts. Results We interviewed 11 of 17 people who participated in PARTNER UP—10 in the month 1 interview and 8 in the month 4 interview. Nearly all participants were motivated to join for consistent and easy access to buprenorphine/naloxone (i.e., MOUD); only a few joined to access PrEP. Most were comfortable accessing healthcare at the SSP because of their relationship with and trust toward SSP staff, and accessing services at the SSP was preferred compared with other healthcare centers. Some participants described that telemedicine allowed them to be honest and share more information because the visits were not in-person and they chose the location, although the initial in-person meeting was helpful to build provider trust and rapport. Most participants found the visit schedule to be feasible, although half described needing to reschedule at least once. Nearly all participants who were interviewed intended to continue with MOUD after the program ended, whereas none were interested in continuing with PrEP. Conclusions Participant narratives suggest that the PARTNER UP telemedicine program was acceptable and feasible. Future studies should continue to explore the benefits of embedding both PrEP and MOUD into SSPs with larger numbers of participants. Trial registration Clinicaltrials.gov Identifier: NCT04521920.

People who use illicit drugs (PWUDs) have been identified as a key at-risk group for tuberculosis (TB). Examination of illicit drug use networks has potential to assess the risk of TB exposure and disease progression. Research also is needed to assess mechanisms for accelerated TB transmission in this population. This study aims to 1) assess the rate of TB exposure, risk of disease progression, and disease burden among PWUD; 2) estimate the proportion of active TB cases resulting from recent transmission within this network; and 3) evaluate whether PWUD with TB disease have physiologic characteristics associated with more efficient TB transmission. Our cross-sectional, observational study aims to assess TB transmission through illicit drug use networks, focusing on methamphetamine and Mandrax (methaqualone) use, in a high TB burden setting and identify mechanisms underlying accelerated transmission. We will recruit and enroll 750 PWUD (living with and without HIV) through respondent driven sampling in Worcester, South Africa. Drug use will be measured through self-report and biological measures, with sputum specimens collected to identify TB disease by Xpert Ultra (Cepheid) and mycobacterial culture. We will co-enroll those with microbiologic evidence of TB disease in Aim 2 for molecular and social network study. Whole genome sequencing of Mycobacteria tuberculosis ( Mtb ) specimens and social contact surveys will be done for those diagnosed with TB. For Aim 3, aerosolized Mtb will be compared in individuals with newly diagnosed TB who do and do not smoke illicit drug. Knowledge from this study will provide the basis for a strategy to interrupt TB transmission in PWUD and provide insight into how this fuels overall community transmission. Results have potential for informing interventions to reduce TB spread applicable to high TB and HIV burden settings. Trial registration: Clinicaltrials.gov Registration Number: NCT041515602 . Date of Registration: 5 November 2019.

Background People who inject drugs (PWID) are at high risk for opioid overdose and infectious diseases including HIV. We piloted PARTNER UP, a telemedicine-based program to provide PWID with medication for opioid use disorder (MOUD) with buprenorphine/naloxone (bup/nx) and oral pre-exposure prophylaxis (PrEP) with tenofovir disoproxil fumarate/emtricitabine through two syringe services programs (SSP) in North Carolina. We present overall results from this project, including participant retention rates and self-reported medication adherence. Methods Study participants met with a provider for an initial in-person visit at the SSP, followed by weekly telemedicine visits in month 1 and then monthly until program end at month 6. Participants were asked to start both MOUD and PrEP at initiation but could choose to discontinue either at any point during the study. Demographics and health history including substance use, sexual behaviors, and prior use of MOUD/PrEP were collected at baseline. Follow-up surveys were conducted at 3- and 6-months to assess attitudes towards MOUD and PrEP, change in opioid use and sexual behaviors, and for self-reported medication adherence. Participant retention was measured by completion of visits; provider notes were used to assess whether the participant reported continuation of medication. Results Overall, 17 persons were enrolled and started on both bup/nx and PrEP; the majority self-identified as white and male. At 3 months, 13 (76%) remained on study; 10 (77%) reported continuing with both MOUD and PrEP, 2 (15%) with bup/nx only, and 1 (8%) with PrEP only. At 6 months, 12 (71%) remained on study; 8 (67%) reported taking both bup/nx and PrEP, and 4 (33%) bup/nx only. Among survey participants, opioid use and HIV risk behaviors decreased. Nearly all reported taking bup/nx daily; however, self-reported daily adherence to PrEP was lower and declined over time. The most common reason for not continuing PrEP was feeling not at risk for acquiring HIV. Conclusions Our study results show that MOUD and PrEP can be successfully administered via telemedicine in SSPs. PrEP appears to be a lower priority for participants with decreased continuation and adherence. Low perception of HIV risk was a reason for not continuing PrEP, possibly mitigated by MOUD use. Future studies including helping identify PWID at highest need for PrEP are needed. Trial registration Providing Suboxone and PrEP Using Telemedicine, NCT04521920. Registered 18 August 2020. https://clinicaltrials.gov/study/NCT04521920?term=mehri%20mckellar&rank=2 .

Globally, cannabis is the most commonly used illicit drug, with disproportionately high use among persons with HIV. Despite advances in HIV care, nearly half of persons living with HIV continue to experience neurocognitive deficits or impairments that may have negative impacts on their daily function. Chronic cannabis use may play a role in the development or exacerbation of these impairments. Here we present a review summarizing existing research detailing the effect of cannabis use associated with the neuropathogenesis of HIV. We examine evidence for possible additive or synergistic effects of HIV infection and cannabis use on neuroHIV in both the preclinical and adult human literatures, including in vitro studies, animal models, clinical neuroimaging research, and studies examining the cognitive effects of cannabis. We discuss the limitations of existing research, including methodological challenges involved with clinical research with human subjects. We identify gaps in the field and propose critical research questions to advance our understanding of how cannabis use affects neuroHIV. Graphical Abstract

Background Delay discounting has been proposed as a behavioral marker of substance use disorders. Innovative analytic approaches that integrate information from multiple neuroimaging modalities can provide new insights into the complex effects of drug use on the brain. This study implemented a supervised multimodal fusion approach to reveal neural networks associated with delay discounting that distinguish persons with and without cocaine use disorder (CUD). Methods Adults with (n = 35) and without (n = 37) CUD completed a magnetic resonance imaging (MRI) scan to acquire high-resolution anatomical, resting-state functional, and diffusion-weighted images. Pre-computed features from each data modality included whole-brain voxel-wise maps for gray matter volume, fractional anisotropy, and regional homogeneity, respectively. With delay discounting as the reference, multimodal canonical component analysis plus joint independent component analysis was used to identify co-alterations in brain structure and function. Results The sample was 58% male and 78% African–American. As expected, participants with CUD had higher delay discounting compared to those without CUD. One joint component was identified that correlated with delay discounting across all modalities, involving regions in the thalamus, dorsal striatum, frontopolar cortex, occipital lobe, and corpus callosum. The components were negatively correlated with delay discounting, such that weaker loadings were associated with higher discounting. The component loadings were lower in persons with CUD, meaning the component was expressed less strongly. Conclusions Our findings reveal structural and functional co-alterations linked to delay discounting, particularly in brain regions involved in reward salience, executive control, and visual attention and connecting white matter tracts. Importantly, these multimodal networks were weaker in persons with CUD, indicating less cognitive control that may contribute to impulsive behaviors.

White matter hyperintensities (WMH), a marker of cerebral small vessel disease and predictor of cognitive decline, are observed at higher rates in persons with HIV (PWH). The use of cocaine, a potent central nervous system stimulant, is disproportionately common in PWH and may contribute to WMH. The sample included of 110 PWH on antiretroviral therapy. Fluid-attenuated inversion recovery (FLAIR) and T1-weighted anatomical MRI scans were collected, along with neuropsychological testing. FLAIR images were processed using the Lesion Segmentation Toolbox. A hierarchical regression model was run to investigate predictors of WMH burden [block 1: demographics; block 2: cerebrovascular disease (CVD) risk; block 3: lesion burden]. The sample was 20% female and 79% African American with a mean age of 45.37. All participants had persistent HIV viral suppression, and the median CD4 T-cell count was 750. Nearly a third (29%) currently used cocaine regularly, with an average of 23.75 (SD = 20.95) days in the past 90. In the hierarchical linear regression model, cocaine use was a significant predictor of WMH burden (β = .28). WMH burden was significantly correlated with poorer cognitive function (r = -0.27). Finally, higher WMH burden was significantly associated with increased serum concentrations of interferon-γ-inducible protein 10 (IP-10) but lower concentrations of myeloperoxidase (MPO); however, these markers did not differ by COC status. WMH burden is associated with poorer cognitive performance in PWH. Cocaine use and CVD risk independently contribute to WMH, and addressing these conditions as part of HIV care may mitigate brain injury underlying neurocognitive impairment.

People living with human immunodeficiency virus (PLWH) often have neurocognitive impairment. However, findings on HIV‐related differences in brain network function underlying these impairments are inconsistent. One principle frequently absent from these reports is that brain function is largely emergent from brain structure. PLWH commonly have degraded white matter; we hypothesized that functional communities connected by degraded white matter tracts would show abnormal functional connectivity. We measured white matter integrity in 69 PLWH and 67 controls using fractional anisotropy (FA) in 24 intracerebral white matter tracts. Then, among tracts with degraded FA, we identified gray matter regions connected to these tracts and measured their functional connectivity during rest. Finally, we identified cognitive impairment related to these structural and functional connectivity systems. We found HIV‐related decreased FA in the corpus callosum body (CCb), which coordinates activity between the left and right hemispheres, and corresponding increases in functional connectivity. Finally, we found that individuals with impaired cognitive functioning have lower CCb FA and higher CCb functional connectivity. This result clarifies the functional relevance of the corpus callosum in HIV and provides a framework in which abnormal brain function can be understood in the context of abnormal brain structure, which may both contribute to cognitive impairment. People living with human immunodeficiency virus have degraded white matter in the body of the corpus callosum. This is associated with decreased functional connectivity among regions connected to the body of the corpus callosum. These brain differences are both associated with impaired cognition.

Cocaine use is disproportionately prevalent in people with HIV (PWH) and is known to potentiate HIV neuropathogenesis. As both HIV and cocaine have well-documented cortico-striatal effects, PWH who use cocaine and have a history of immunosuppression may exhibit greater FC deficits compared to PWH without these conditions. However, research investigating the legacy effects of HIV immunosuppression (i.e., a history of AIDS) on cortico-striatal functional connectivity (FC) in adults with and without cocaine use is sparse. Resting-state functional magnetic resonance imaging (fMRI) and neuropsychological assessment data from 273 adults were analyzed to examine FC in relation to HIV disease: HIV-negative ( n  = 104), HIV-positive with nadir CD4 ≥ 200 ( n  = 96), HIV-positive with nadir CD4 < 200 (AIDS; n  = 73), and cocaine use (83 COC and 190 NON). Using independent component analysis/dual regression, FC was assessed between the basal ganglia network (BGN) and five cortical networks: dorsal attention network (DAN), default mode network, left executive network, right executive network, and salience network. There were significant interaction effects such that AIDS-related BGN-DAN FC deficits emerged in COC but not in NON participants. Independent of HIV, cocaine effects emerged in FC between the BGN and executive networks. Disruption of BGN-DAN FC in AIDS/COC participants is consistent with cocaine potentiation of neuro-inflammation and may be indicative of legacy HIV immunosuppressive effects. The current study bolsters previous findings linking HIV and cocaine use with cortico-striatal networking deficits. Future research should consider the effects of the duration of HIV immunosuppression and early treatment initiation.

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.