Soluble Plasma Proteins of Tumor Necrosis Factor and Immunoglobulin Superfamilies Reveal New Insights into Immune Regulation in People with HIV and Opioid Use Disorder.

People with HIV (PWH) frequently suffer from Opioid (OP) Use Disorder (OUD). In an investigation of the impact of OUD on underlying immune dysfunction in PWH, we previously reported that OP use exacerbates inflammation in virally controlled PWH followed in the Infectious Diseases Elimination Act (IDEA) Syringe Services Program (SSP). Unexpectedly, Flu vaccination-induced antibody responses in groups with OUD were superior to PWH without OUD. Here, we investigated the profile of 48 plasma biomarkers comprised of TNF and Ig superfamily (SF) molecules known to impact interactions between T and B cells in 209 participants divided into four groups: (1) HIV+OP+, (2) HIV-OP+, (3) HIV+OP-, and (4) HIV-OP-. The differential expression of the top eight molecules ranked by median values in individual Groups 1-3 in comparison to Group 4 was highly significant. Both OP+ groups 1 and 2 had higher co-stimulatory TNF SF molecules, including 4-1BB, OX-40, CD40, CD30, and 4-1BBL, which were found to positively correlate with Flu Ab titers. In contrast, HIV+OP- exhibited a profile dominant in Ig SF molecules, including PDL-2, CTLA-4, and Perforin, with PDL-2 showing a negative correlation with Flu vaccine titers. These findings are relevant to vaccine development in the fields of HIV and OUD.

PrEP for people who use opioids: A NIDA clinical trials network survey study in Southern U.S. cities where HIV incidence is high.

BACKGROUND: People who use opioids (PWUO) are at increased risk for HIV. Pre-exposure prophylaxis (PrEP) is effective but underutilized as HIV prevention among PWUO. This study examined predictors of willingness to take daily oral PrEP and long-acting injectable (LAI) PrEP among PWUO across eight Southern urban cities with high HIV incidence. METHODS: HIV-negative PWUO (N = 308) seeking services in community-based programs participated in this cross-sectional survey study. Measures included demographics, sexual risk behavior, substance use frequency, and awareness of and willingness to take oral and injectable PrEP. Data were analyzed using mixed-effects models. RESULTS: Willingness to take daily oral and LAI PrEP was moderately high (69.16% and 62.02%, respectively). Half had heard of PrEP, but only 4% had ever taken it. Only education and condomless vaginal sex predicted willingness to take oral PrEP. Only education predicted willingness to take LAI PrEP. Polysubstance use was prevalent, with substantial proportions of PWUO reporting frequent use of injection drugs (opioids or stimulants, 79.5%), non-injection opioids (73.3%), non-injection stimulants (71.1%), cannabis (62.6%), and hazardous drinking (29.6%). About 20% reported past-year condomless anal sex, and one-third reported past-year condomless vaginal sex. CONCLUSIONS: PWUO in this study were amenable to PrEP, particularly in light of education and condomless vaginal sex. Careful consideration for matching PrEP messaging to the PWUO audience is needed. PrEP promotion should expand beyond men who have sex with men to include groups such as these predominantly heterosexual, polysubstance-using PWUO with HIV risk who were open to both formulations of PrEP.

Opioids exacerbate inflammation in people with well-controlled HIV.

Introduction: People with HIV (PWH) are known to have underlying inflammation and immune activation despite virologic control. Substance use including opioid dependence is common in this population and is associated with increased morbidity and reduced lifespan. The primary objective of the present study termed opioid immunity study (OPIS), was to investigate the impact of chronic opioids in PWH. Methods: The study recruited people with and without HIV who had opioid use disorder (OUD). Study participants (n=221) were categorized into four groups: HIV+OP+, n=34; HIV-OP+, n=66; HIV+OP-, n=55 and HIV-OP-, n=62 as controls. PWH were virally suppressed on ART and those with OUD were followed in a syringe exchange program with confirmation of OP use by urine drug screening. A composite cytokine score was developed for 20 plasma cytokines that are linked to inflammation. Cellular markers of immune activation (IA), exhaustion, and senescence were determined in CD4 and CD8 T cells. Regression models were constructed to examine the relationships of HIV status and opioid use, controlling for other confounding factors. Results: HIV+OP+ participants exhibited highest inflammatory cytokines and cellular IA, followed by HIV-OP+ for inflammation and HIV+OP- for IA. Inflammation was found to be driven more by opioid use than HIV positivity while IA was driven more by HIV than opioid use. In people with OUD, expression of CD38 on CD28-CD57+ senescent-like T cells was elevated and correlated positively with inflammation. Discussion: Given the association of inflammation with a multitude of adverse health outcomes, our findings merit further investigations to understand the mechanistic pathways involved.

A study protocol for Project I-Test: a cluster randomized controlled trial of a practice coaching intervention to increase HIV testing in substance use treatment programs.

Background People with substance use disorders are vulnerable to acquiring HIV. Testing is fundamental to diagnosis, treatment, and prevention; however, in the past decade, there has been a decline in the number of substance use disorder (SUD) treatment programs offering on-site HIV testing. Fewer than half of SUDs in the United States offer on-site HIV testing. In addition, nearly a quarter of newly diagnosed cases have AIDS at the time of diagnosis. Lack of testing is one of the main reasons that annual HIV incidences have remained constant over time. Integration of HIV testing with testing for HCV, an infection prevalent among persons vulnerable to HIV infection, and in settings where they receive health services, including opioid treatment programs (OTPs), is of great public health importance. Methods/Design In this 3-arm cluster-RCT of opioid use disorders treatment programs, we test the effect of two evidence-based "practice coaching" (PC) interventions on: the provision and sustained implementation of on-site HIV testing, on-site HIV/HCV testing, and linkage to care. Using the National Survey of Substance Abuse Treatment Services data available from SAMHSA, 51 sites are randomly assigned to one of the three conditions: practice coach facilitated structured conversations around implementing change, with provision of resources and documents to support the implementation of (1) HIV testing only, or (2) HIV/HCV testing, and (3) a control condition that provides a package with information only. We collect quantitative (e,g., HIV and HCV testing at six-month-long intervals) and qualitative site data near the time of randomization, and again approximately 7-12 months after randomization. Discussion Innovative and comprehensive approaches that facilitate and promote the adoption and sustainability of HIV and HCV testing in opioid treatment programs are important for addressing and reducing HIV and HCV infection rates. This study is one of the first to test organizational approaches (practice coaching) to increase HIV and HIV/HCV testing and linkage to care among individuals receiving treatment for opioid use disorder. The study may provide valuable insight and knowledge on the multiple levels of intervention that, if integrated, may better position OTPs to improve and sustain testing practices and improve population health. Trial registration ClinicalTrials.gov: NCT03135886. (02 05 2017).

Structural equation model of intersectional microaggressions, discrimination, resilience, and mental health among black women with hiv.

OBJECTIVE: Compared to non-Black women, Black women in the United States are more likely to be diagnosed with HIV, living with HIV, and have suboptimal HIV outcomes, disparities largely linked to structural and psychosocial factors that may impact mental health. METHOD: 151 Black women living with HIV (BWLWH) enrolled in a longitudinal cohort study completed baseline assessments between October 2019 and January 2020 in the Southeastern United States. Measures captured microaggressions (gendered-racial, HIV, and Lesbian/Gay/Bisexual/Transgender/Queer), "macro" discrimination acts (gender, race, HIV, sexual orientation), resilience factors (self-efficacy, trait resilience, posttraumatic growth, positive religious coping, and social support), and mental health (depressive symptoms, posttraumatic stress disorder (PTSD) symptoms, and posttraumatic cognitions). Four structural equation models were estimated with latent discrimination (LD), latent microaggression (LM), and latent resilience (LR) as predictors and depressive symptoms, PTSD symptoms, posttraumatic cognitions, and latent mental health (LH) as outcomes. Indirect pathways from LD and LM via LR and LR as a moderator were estimated. RESULTS: Models fit well based on indices. There were significant direct pathways from LM and LR to depressive symptoms, posttraumatic cognitions, and LH and a significant direct pathway from LM to PTSD symptoms, but not from LD to any mental health outcome. Indirect pathways were not significant. However, LR moderated the relationships between both LM and LD with PTSD symptoms. CONCLUSION: Intersectional microaggressions and resilience factors may play key roles in BWLWH's mental health. Research is needed to examine these pathways overtime and provide opportunities to improve mental health and HIV outcomes among BWLWH. (PsycInfo Database Record (c) 2023 APA, all rights reserved).

Community voices on factors influencing COVID-19 concerns and health decisions among racial and ethnic minorities in the school setting.

Racial and ethnic minority communities have been disproportionately affected by COVID-19, but the uptake of COVID-19 mitigation strategies like vaccination and testing have been slower in these populations. With the continued spread of COVID-19 while in-person learning is a priority, school-aged youth and their caregivers must make health-related decisions daily to ensure health at school. It is critical to understand factors associated with COVID-related health decisions such as vaccination, testing, and other health behaviors (e.g., wearing masks, hand washing). Community-engaged campaigns are necessary to overcome barriers to these health behaviors and promote health equity. The aim of this study was to examine COVID-19-related concerns and influences on health decisions in middle and high schools serving primarily racial and ethnic minority, low-income families. Seven focus groups were conducted with school staff, parents, and students (aged 16 years and older). Qualitative data were analyzed using a general inductive approach. Factors related to COVID-19 concerns and health decisions centered on (1) vaccine hesitancy, (2) testing hesitancy, (3) developmental stage (i.e., ability to engage in health behaviors based on developmental factors like age), (4) cultural and family traditions and beliefs, (5) compatibility of policies and places with recommended health behaviors, (6) reliability of information, and (7) perceived risk. We explore sub-themes in further detail. It is important to understand the community's level of concern and identify factors that influence COVID-19 medical decision making to better address disparities in COVID-19 testing and vaccination uptake.

Neighborhood Characteristics, Intersectional Discrimination, Mental Health, and HIV Outcomes Among Black Women Living With HIV, Southeastern United States, 2019‒2020.

Objectives. To examine the effects of within-neighborhood and neighboring characteristics on discrimination, stigma, mental health, and HIV outcomes among Black women living with HIV (BWLWH). Methods. A total of 151 BWLWH in a southeastern US city provided baseline data (October 2019‒January 2020) on experienced microaggressions and discrimination (race-, gender-, sexual orientation-, or HIV-related), mental health (e.g., depression, posttraumatic stress disorder), and HIV outcomes (e.g., viral load, antiretroviral therapy adherence). Neighborhood characteristics by census tract were gathered from the American Community Survey and the National Center for Charitable Statistics. Spatial econometrics guided the identification strategy, and we used the maximum likelihood technique to estimate relationships between a number of predictors and outcomes. Results. Within-neighborhood and neighboring characteristics (employment, education, crime, income, number of religious organizations, and low-income housing) were significantly related to intersectional stigma, discrimination, mental health, HIV viral load, and medication adherence. Conclusions. Policy, research, and interventions for BWLWH need to address the role of neighborhood characteristics to improve quality of life and HIV outcomes. (Am J Public Health. 2022;112(S4):S433-S443. https://doi.org/10.2105/AJPH.2021.306675).

Care Facilitation Advances Movement Along the Hepatitis C Care Continuum for Persons With Human Immunodeficiency Virus, Hepatitis C, and Substance Use: A Randomized Clinical Trial (CTN-0064).

BACKGROUND: Direct-acting antivirals can cure hepatitis C virus (HCV). Persons with HCV/HIV and living with substance use are disadvantaged in benefiting from advances in HCV treatment. METHODS: In this randomized controlled trial, participants with HCV/HIV were randomized between February 2016 and January 2017 to either care facilitation or control. Twelve-month follow-up assessments were completed in January 2018.Care facilitation group participants received motivation and strengths-based case management addressing retrieval of HCV viral load results, engagement in HCV/HIV care, and medication adherence. Control group participants received referral to HCV evaluation and an offer of assistance in making care appointments. Primary outcome was number of steps achieved along a series of 8 clinical steps (eg, receiving HCV results, initiating treatment, sustained virologic response [SVR]) of the HCV/HIV care continuum over 12 months postrandomization. RESULTS: Three hundred eighty-one individuals were screened and 113 randomized. Median age was 51 years; 58.4% of participants were male and 72.6% were Black/African American. Median HIV-1 viral load was 27 209 copies/mL, with 69% having a detectable viral load. Mean number of steps completed was statistically significantly higher in the intervention group vs controls (2.44 vs 1.68 steps; χ 2 [1] = 7.36, P = .0067). Men in the intervention group completed a statistically significantly higher number of steps than controls. Eleven participants achieved SVR with no difference by treatment group. CONCLUSIONS: The care facilitation intervention increased progress along the HCV/HIV care continuum, as observed for men and not women. Study findings also highlight continued challenges to achieve individual-patient SVR and population-level HCV elimination. CLINICAL TRIALS REGISTRATION: NCT02641158.

The nurse's load: early-life exposure to brood-rearing affects behavior and lifespan in honey bees (Apis mellifera).

Long-lived honey bees (Apis mellifera) develop in fall. This pattern may be explained by reduced nurse loads. When the amount of brood in colonies declines as a function of adverse foraging conditions, adult bees build up surplus nutrient stores that include vitellogenin, a behavioral affector protein that also can increase lifespan. Although the seasonal reduction in exposure to nursing tasks predictably results in vitellogenin accumulation, the assumption that long-lived adults thereby develop is confounded by a concomitant decline in foraging effort. Foraging activity reduces lifespan, and is influenced by colony resource consumption, brood pheromones, availability of nectar and pollen, and weather. Here, we perform the first controlled experiment where the nursing environment of pre-foraging sister bees was set to vary, while their foraging environment later was set to be the same. We measure vitellogenin, age at foraging onset and lifespan. We establish that reduced brood-rearing increases vitellogenin levels, and delays foraging onset and death. Longevity is largely explained by the effect of nursing on the onset of foraging behavior, but is also influenced by the level of brood-rearing independent of behavioral change. Our findings are consistent with the roles of vitellogenin in regulation of honey bee behavior and lifespan.

The gene vitellogenin has multiple coordinating effects on social organization.

Temporal division of labor and foraging specialization are key characteristics of honeybee social organization. Worker honeybees (Apis mellifera) initiate foraging for food around their third week of life and often specialize in collecting pollen or nectar before they die. Variation in these fundamental social traits correlates with variation in worker reproductive physiology. However, the genetic and hormonal mechanisms that mediate the control of social organization are not understood and remain a central question in social insect biology. Here we demonstrate that a yolk precursor gene, vitellogenin, affects a complex suite of social traits. Vitellogenin is a major reproductive protein in insects in general and a proposed endocrine factor in honeybees. We show by use of RNA interference (RNAi) that vitellogenin gene activity paces onset of foraging behavior, primes bees for specialized foraging tasks, and influences worker longevity. These findings support the view that the worker specializations that characterize hymenopteran sociality evolved through co-option of reproductive regulatory pathways. Further, they demonstrate for the first time how coordinated control of multiple social life-history traits can originate via the pleiotropic effects of a single gene that affects multiple physiological processes.