Loss of HIV-1–specific CD8+ T Cell Proliferation after Acute HIV-1 Infection and Restoration by Vaccine-induced HIV-1–specific CD4+ T Cells

Virus-specific CD8+ T cells are associated with declining viremia in acute human immunodeficiency virus (HIV)1 infection, but do not correlate with control of viremia in chronic infection, suggesting a progressive functional defect not measured by interferon γ assays presently used. Here, we demonstrate that HIV-1–specific CD8+ T cells proliferate rapidly upon encounter with cognate antigen in acute infection, but lose this capacity with ongoing viral replication. This functional defect can be induced in vitro by depletion of CD4+ T cells or addition of interleukin 2–neutralizing antibodies, and can be corrected in chronic infection in vitro by addition of autologous CD4+ T cells isolated during acute infection and in vivo by vaccine-mediated induction of HIV-1–specific CD4+ T helper cell responses. These data demonstrate a loss of HIV-1–specific CD8+ T cell function that not only correlates with progressive infection, but also can be restored in chronic infection by augmentation of HIV-1–specific T helper cell function. This identification of a reversible defect in cell-mediated immunity in chronic HIV-1 infection has important implications for immunotherapeutic interventions

Impaired Hepatitis C Virus-Specific T Cell Responses and Recurrent Hepatitis C Virus in HIV Coinfection

BACKGROUND: Hepatitis C virus (HCV)-specific T cell responses are critical for spontaneous resolution of HCV viremia. Here we examined the effect of a lymphotropic virus, HIV-1, on the ability of coinfected patients to maintain spontaneous control of HCV infection. METHODS AND FINDINGS: We measured T cell responsiveness by lymphoproliferation and interferon-γ ELISPOT in a large cohort of HCV-infected individuals with and without HIV infection. Among 47 HCV/HIV-1-coinfected individuals, spontaneous control of HCV was associated with more frequent HCV-specific lymphoproliferative (LP) responses (35%) compared to coinfected persons who exhibited chronic HCV viremia (7%, p = 0.016), but less frequent compared to HCV controllers who were not HIV infected (86%, p = 0.003). Preservation of HCV-specific LP responses in coinfected individuals was associated with a higher nadir CD4 count (r (2) = 0.45, p < 0.001) and the presence and magnitude of the HCV-specific CD8(+) T cell interferon-γ response (p = 0.0014). During long-term follow-up, recurrence of HCV viremia occurred in six of 25 coinfected individuals with prior control of HCV, but in 0 of 16 HIV-1-negative HCV controllers (p = 0.03, log rank test). In these six individuals with recurrent HCV viremia, the magnitude of HCV viremia following recurrence inversely correlated with the CD4 count at time of breakthrough (r = −0.94, p = 0.017). CONCLUSIONS: These results indicate that HIV infection impairs the immune response to HCV—including in persons who have cleared HCV infection—and that HIV-1-infected individuals with spontaneous control of HCV remain at significant risk for a second episode of HCV viremia. These findings highlight the need for repeat viral RNA testing of apparent controllers of HCV infection in the setting of HIV-1 coinfection and provide a possible explanation for the higher rate of HCV persistence observed in this population

Microbial Translocation Is Associated with Increased Monocyte Activation and Dementia in AIDS Patients

Elevated plasma lipopolysaccharide (LPS), an indicator of microbial translocation from the gut, is a likely cause of systemic immune activation in chronic HIV infection. LPS induces monocyte activation and trafficking into brain, which are key mechanisms in the pathogenesis of HIV-associated dementia (HAD). To determine whether high LPS levels are associated with increased monocyte activation and HAD, we obtained peripheral blood samples from AIDS patients and examined plasma LPS by Limulus amebocyte lysate (LAL) assay, peripheral blood monocytes by FACS, and soluble markers of monocyte activation by ELISA. Purified monocytes were isolated by FACS sorting, and HIV DNA and RNA levels were quantified by real time PCR. Circulating monocytes expressed high levels of the activation markers CD69 and HLA-DR, and harbored low levels of HIV compared to CD4+ T-cells. High plasma LPS levels were associated with increased plasma sCD14 and LPS-binding protein (LBP) levels, and low endotoxin core antibody levels. LPS levels were higher in HAD patients compared to control groups, and were associated with HAD independently of plasma viral load and CD4 counts. LPS levels were higher in AIDS patients using intravenous heroin and/or ethanol, or with Hepatitis C virus (HCV) co-infection, compared to control groups. These results suggest a role for elevated LPS levels in driving monocyte activation in AIDS, thereby contributing to the pathogenesis of HAD, and provide evidence that cofactors linked to substance abuse and HCV co-infection influence these processes

"You're kind of at war with yourself as a nurse": Perspectives of inpatient nurses on treating people who present with a comorbid opioid use disorder.

BackgroundIn the midst of an opioid epidemic, health care workers are encountering an increasing number of patients who have opioid use disorder in addition to complex social, behavioral and medical issues. Of all the clinicians in the hospital, nurses spend the most time with hospitalized patients who have opioid use disorder, yet there has been little research exploring their experiences in caring for this population. The objective of this study was to assess the attitudes, perceptions, and training needs of nurses in the inpatient setting when caring for patients who have opioid use disorder.MethodsOne-on-one in-depth interviews were conducted with nurses working at a large academic medical center in Boston, MA, using a semi-structured interview guide. Nurses were recruited via email notifications and subsequent snowball sampling. Interviews were recorded, transcribed and analyzed using a grounded theory approach.ResultsData from in-depth interviews with 22 nurses were grouped into six themes: (1) stigma, (2) assessing & treating pain, (3) feelings of burn out, (4) communication between providers, (5) safety & security, and (6) opportunities for change. These themes were organized within four ecological levels of the Socio-Ecological Model: I) societal context, II) hospital environment, III) interpersonal interactions, and IV) individual factors. Nurses were cognizant of the struggles that patients who have opioid use disorder confront during hospitalization such as pain, withdrawal and stigma, and elaborated on how these challenges translate to professional and emotional strain among nurses. Nurses offered recommendations by which the hospital could streamline care for this population, including expanded role support for nurses and more structured policies regarding care for patients who present with a comorbid opioid use disorder.ConclusionOur results highlight the need for the development of programs targeting both organizational culture and the inpatient nurse quality of life to ultimately enhance quality of care for patients who present with opioid use disorder

Heterogeneity in Jail Nursing Medical Intake Forms: A Content Analysis

Despite high prevalence of infectious diseases and substance use disorders in jails, there are limited guidelines for the nursing intake process in this setting. We performed a content analysis of nursing intake forms used at each of the 14 Massachusetts county jails, focusing on infectious disease and substance use disorder. Only 85% of jails offered HIV testing during nursing intake and 50% of jails offered hepatitis C testing. Preventive interventions such as vaccines or pre-exposure prophylaxis therapy were infrequently offered during nursing intake. Screening for substance use disorder was present on the majority of intake forms, but only 23% of intake forms inquired about ongoing medication-assisted treatment for opioid use disorder. The results reflect heterogeneity in nursing intake forms, highlighting missed opportunities for public health interventions

Hospitalization outcomes of people who use drugs: One size does not fit all

People with opioid use disorder (OUD) have worse hospital outcomes and higher healthcare costs. There are rising reports of people with OUD also using other classes of drugs, however patterns of substance use have not been evaluated for differential effects on hospital outcomes. We performed a data-analysis of the Healthcare Utilization Project's National Readmissions Database, examining the effects of patterns of substance use, age, gender, and diagnosis on the outcomes of Against Medical Advice (AMA) discharges and 30-day readmissions. About one-third of the patients with OUD who were admitted to the hospital had at least one additional substance use disorder (SUD). Thirteen percent of persons with OUD were discharged AMA, and 12% were readmitted to the hospital within 30 days of discharge. Compared to people with OUD alone, people who used stimulants had increased odds of AMA discharge (aOR 1.83 (CI 1.73, 1.96)) and 30-day readmission (aOR 1.30 (95% CI 1.23, 1.37)). Multiple concomitant substance use disorders were associated with increased odds of AMA discharge and 30-day readmission. Conclusions: People with OUD have high rates of both AMA discharges and 30 day-readmissions, and there is a layered effect of increasing co-occurring SUDs leading to worse hospitalization outcomes. The heterogeneity of drug use patterns needs to be considered when developing strategies to improve health care outcomes for people with substance use disorder. •One third of people with opioid use disorder (OUD) admitted to the hospital in 2013 had another substance use disorder.•Thirteen percent of people with OUD were discharged against medical advice, and 12% of people were readmitted within 30 days.•Co-morbid drug use disorders were associated with increased odds of AMA discharge and 30-day readmission

"You're kind of at war with yourself as a nurse": perspectives of inpatient nurses on treating people who present with a comorbid opioid use disorder.

BACKGROUND: In the midst of an opioid epidemic, health care workers are encountering an increasing number of patients who have opioid use disorder in addition to complex social, behavioral and medical issues. Of all the clinicians in the hospital, nurses spend the most time with hospitalized patients who have opioid use disorder, yet there has been little research exploring their experiences in caring for this population. The objective of this study was to assess the attitudes, perceptions, and training needs of nurses in the inpatient setting when caring for patients who have opioid use disorder. METHODS: One-on-one in-depth interviews were conducted with nurses working at a large academic medical center in Boston, MA, using a semi-structured interview guide. Nurses were recruited via email notifications and subsequent snowball sampling. Interviews were recorded, transcribed and analyzed using a grounded theory approach. RESULTS: Data from in-depth interviews with 22 nurses were grouped into six themes: (1) stigma, (2) assessing & treating pain, (3) feelings of burn out, (4) communication between providers, (5) safety & security, and (6) opportunities for change. These themes were organized within four ecological levels of the Socio-Ecological Model: I) societal context, II) hospital environment, III) interpersonal interactions, and IV) individual factors. Nurses were cognizant of the struggles that patients who have opioid use disorder confront during hospitalization such as pain, withdrawal and stigma, and elaborated on how these challenges translate to professional and emotional strain among nurses. Nurses offered recommendations by which the hospital could streamline care for this population, including expanded role support for nurses and more structured policies regarding care for patients who present with a comorbid opioid use disorder. CONCLUSION: Our results highlight the need for the development of programs targeting both organizational culture and the inpatient nurse quality of life to ultimately enhance quality of care for patients who present with opioid use disorder

The Impact of Incarceration on Readmissions Among Patients With Inflammatory Bowel Disease Hospitalized at a Community Hospital

Background and Aims: Individuals who are incarcerated often have limited access to first-line treatment and comprehensive health care. In this study, we aimed to compare the frequency of readmissions among patients with inflammatory bowel disease (IBD) receiving care at a community hospital who were and were not incarcerated at the time of hospitalization. Methods: We analyzed records from Lemuel Shattuck Hospital for all patients admitted between January 1, 2011, and December 31, 2019. Patients with IBD were identified using International Classification of Diseases codes. The primary outcome was all-cause readmission at 1 year following an IBD-related admission. Secondary outcomes were (1) all-cause readmission at 30 days, (2) IBD-related readmission at 30 days, and (3) IBD-related readmission at 1 year. Our indicator of interest was incarceration. Multivariable logistic regression models were built to describe predictors of all-cause readmissions at 1 year. Results: Among the 6511 individuals hospitalized at Lemuel Shattuck Hospital between 2011 and 2019, 90 individuals (1.4%) had International Classification of Diseases codes for IBD, either ulcerative colitis (n = 44) and/or Crohn’s disease (n = 39). Half (n = 46) of patients with IBD were incarcerated during hospital admission. Individuals who were incarcerated had a higher rate of all-cause readmissions at 1 year than those who were not incarcerated at the time of hospitalization (76.0% vs 41.5%, P = .005). Multivariable analysis showed patients who were incarcerated had 3.98 (95% confidence interval: 1.39–12.78) increased odds of all-cause readmission within 1 year. Conclusion: Our results suggest individuals with IBD who are incarcerated may experience worse health outcomes than individuals who are not incarcerated, adding to a body of literature documenting the negative impact of incarceration on health