HIV Infection and Depression Among Opiate Users in a US Epicenter of the Opioid Epidemic.

Using a mobile research facility, we enrolled 141 opioid users from a neighborhood of Philadelphia, an urban epicenter of the opioid epidemic. Nearly all (95.6%) met DSM-5 criteria for severe opioid use disorder. The prevalence of HIV infection (8.5%) was more than seven times that found in the general population of the city. Eight of the HIV-positive participants (67.0%) reported receiving antiretroviral treatment but almost all of them had unsuppressed virus (87.5%). The majority of participants (57.4%) reported symptoms consistent with major depressive disorder. Severe economic distress (60.3%) and homelessness were common (57%). Polysubstance use was nearly universal, 72.1% had experienced multiple overdoses and prior medication for opioid use disorder (MOUD) treatment episodes (79.9%), but few currently engaged in addiction care. The prevalence, multiplicity and severity of chronic health and socioeconomic problems highlight consequences of the current opioid epidemic and underscore the urgent need to develop integrated models of treatment.

RESUMEN: Utilizando un Centro de Investigación Móvil, inscribimos a 141 usuarios de opioides del vecindario de Filadelfia, un epicentro urbano de la epidemia de opioides. Casi todos (95,6%) cumplieron con los criterios del DSM-5 para el trastorno del uso severo del consumo de opioides. La prevalencia de la infección de VIH (8,5%) fue másﹶ de 7 veces superior a las encontrada en la población general de la ciudad. Ocho de los participantes con VIH positivo (67,0%) reportaron haber recibido tratamiento antirretroviral pero casi todos tuvieron virus no suprimido (87,5%). La mayoría de los participantes (57,4%) informaron síntomas compatibles con el Desorden Depresivo Mayor. La angustia severa por lo económico (60,3%) y las personas sin hogar fueron comunes (57%). El uso de múltiples sustancias fue casi universal, el 721% había experimentado múltiples sobredosis y previos medicamentos para el tratamiento del trastorno por consumo de opioides (MOUD) (79,9%), pero muy pocos estaban comprometidos con la atención a las adicciones. La prevalencia, la multiplicidad y la seriedad de los problemas de salud crónica y los problemas socioeconómicos destacan las consecuencias de la actual epidemia de opioides y subrayan la urgente necesidad de desarrollar nuevos modelos de tratamiento integrados.

Infusion of HIV-1 Nef-expressing astrocytes into the rat hippocampus induces enteropathy and interstitial pneumonitis and increases blood-brain-barrier permeability.

Even though HIV-1 replication can be suppressed by combination antiretroviral therapy (cART) inflammatory processes still occur, contributing to comorbidities. Comorbidities are attributed to variety of factors, including HIV-1 mediated inflammation. Several HIV-1 proteins mediate central nervous system (CNS) inflammation, including Nef. Nef is an early HIV-1 protein, toxic to neurons and glia and is sufficient to cause learning impairment similar to some deficits observed in HIV-1 associated neurocognitive disorders. To determine whether hippocampal Nef expression by astrocytes contributes to comorbidities, specifically peripheral inflammation, we infused Sprague Dawley rats with GFP- (control) or Nef-transfected astrocytes into the right hippocampus. Brain, lung, and ileum were collected postmortem for the measurement of inflammatory markers. Increased blood-brain-barrier permeability and serum IL-1ß levels were detected in the Nef-treated rats. The lungs of Nef-treated rats demonstrated leukocyte infiltration, macrophage upregulation, and enhanced vascular permeability. Ileal tissue showed reactive follicular lymphoid hyperplasia, increased permeability and macrophage infiltration. The intracerebroventricular application of IL-1 receptor antagonist reduced infiltration of immune cells into ileum and lung, indicating the important role of IL-1ß in mediating the spread of inflammation from the brain to other tissues. This suggests that localized expression of a single viral protein, HIV-1 Nef, can contribute to a broader inflammatory response by upregulation of IL-1ß. Further, these results suggest that Nef contributes to the chronic inflammation seen in HIV patients, even in those whose viremia is controlled by cART.