Dynamics of overdose and non-overdose mortality among people living with HIV amidst the illicit drug toxicity crisis in British Columbia.

We sought to characterize overdose and non-overdose mortality among PLWH amidst the illicit drug toxicity crisis in British Columbia, Canada. A population-based analysis of PLWH (age ≥19) in British Columbia accessing healthcare from April 1996 to March 2017 was conducted using data from the Seek and Treat for Optimal Prevention of HIV/AIDS (STOP HIV/AIDS) cohort linkage. Underlying causes of deaths were stratified into overdose and non-overdose causes. We compared (bivariate analysis) health-related characteristics and prescription history between PLWH died of overdose and non-overdose causes between April 2009 and March 2017. Among 9,180 PLWH, we observed 962 deaths (142 [14.7%] overdoses; 820 [85.2%] other causes). Compared to those who died from other causes, those who died of overdose were significantly younger (median age [Q, Q3]: 46 years [42, 52] vs. 54 years [48, 63]); had an indication of chronic pain (35.9% vs. 27.1%) and hepatitis C virus (64.8% vs. 50.4%), but fewer experienced hospitalization in the year before death. PLWH who died were most likely to be prescribed with opioids (>50%) and least likely with opioid agonist therapy (<10%) in a year before death. These findings highlight the syndemic of substance use, HCV, and chronic pain, and how the crisis is unqiuely impacting females and younger people.

Implementation of a regional quality improvement collaborative to improve care of people living with opioid use disorder in a Canadian setting.

BACKGROUND: Although opioid agonist therapy is effective in treating opioid use disorders (OUD), retention in opioid agonist therapy is suboptimal, in part, due to quality of care issues. Therefore, we sought to describe the planning and implementation of a quality improvement initiative aimed at closing gaps in care for people living with OUD through changes to workflow and care processes in Vancouver, Canada. METHODS: The Best-practice in Oral Opioid agoniSt Therapy (BOOST) Collaborative followed the Institute for Healthcare Improvement's Breakthrough Series Collaborative methodology over 18-months. Teams participated in a series of activities and events to support implementing, measuring, and sharing best practices in OAT and OUD care. Teams were assigned monthly implementation scores to monitor their progress on meeting Collaborative aims and implementing changes. RESULTS: Seventeen health care teams from a range of health care practices caring for a total of 4301 patients with a documented diagnosis of OUD, or suspected OUD based on electronic medical record chart data participated in the Collaborative. Teams followed the Breakthrough Series Collaborative methodology closely and reported monthly on a series of standardized process and outcome indicators. The majority of (59%) teams showed some improvement throughout the Collaborative as indicated by implementation scores. CONCLUSIONS: Descriptive data from the evaluation of this initiative illustrates its success. It provides further evidence to support the implementation of quality improvement interventions to close gaps in OUD care processes and treatment outcomes for people living with OUD. This system-level approach has been spread across British Columbia and could be used by other jurisdictions facing similar overdose crises.

Retention in care and mortality trends among patients receiving comprehensive care for HIV infection: a retrospective cohort study.

BACKGROUND: Studies examining the relation between comprehensive care and health outcomes associated with comorbidities unrelated to HIV infection have focused mainly on the health outcomes of HIV-infected people and comorbid substance use disorders. We aimed to assess the impact of retention in comprehensive HIV infection care on overall, AIDS-related and non-AIDS-related mortality. METHODS: Using a retrospective cohort design, we collected data for HIV-infected patients aged 19 years or more who first visited a comprehensive HIV infection clinic in Vancouver between Jan. 1, 2004, and Dec. 31, 2014. We defined retention in care as visit constancy (whether the patient attended the clinic at least once per given period) of 75% or greater. We used Poisson regression modelling to examine mortality trends. We performed Cox proportional hazards modelling to assess survival by retention during the first year of follow-up and identify factors associated with death. RESULTS: A total of 2101 patients were included in the study. Of the 2101, 1340 (63.8%) were retained in the first year of care, and 271 (12.9%) died during the study period. Among the 264 cases in which the cause of death was known, although the primary underlying cause of death (74 [28.0%]) was AIDS-related, half of all AIDS-related deaths (37/74 [50%]) occurred early in the study (2004-2007). In later years, most deaths (147/184 [79.9%]) were non-AIDS-related. Overall mortality was significantly reduced among patients with higher retention in care during the first year of follow-up (per 20% increase in visit constancy; adjusted hazard ratio [HR] 0.87, 95% confidence interval [CI] 0.79-0.96). Higher retention was also associated with reduced risk of AIDS-related death (adjusted HR 0.79, 95% CI 0.64-0.97). INTERPRETATION: Although there was an overall trend toward decreased AIDS-related mortality over time, retention in care markedly decreased the likelihood of death. Maintaining patient engagement in comprehensive ancillary care is a patient-centred way of decreasing mortality rates among HIV-infected people.

HERV-K-specific T cells eliminate diverse HIV-1/2 and SIV primary isolates.

The genetic diversity of HIV-1 represents a major challenge in vaccine development. In this study, we establish a rationale for eliminating HIV-1-infected cells by targeting cellular immune responses against stable human endogenous retroviral (HERV) antigens. HERV DNA sequences in the human genome represent the remnants of ancient infectious retroviruses. We show that the infection of CD4+ T cells with HIV-1 resulted in transcription of the HML-2 lineage of HERV type K [HERV-K(HML-2)] and the expression of Gag and Env proteins. HERV-K(HML-2)-specific CD8+ T cells obtained from HIV-1-infected human subjects responded to HIV-1-infected cells in a Vif-dependent manner in vitro. Consistent with the proposed mode of action, a HERV-K(HML-2)-specific CD8+ T cell clone exhibited comprehensive elimination of cells infected with a panel of globally diverse HIV-1, HIV-2, and SIV isolates in vitro. We identified a second T cell response that exhibited cross-reactivity between homologous HIV-1-Pol and HERV-K(HML-2)-Pol determinants, raising the possibility that homology between HIV-1 and HERVs plays a role in shaping, and perhaps enhancing, the T cell response to HIV-1. This justifies the consideration of HERV-K(HML-2)-specific and cross-reactive T cell responses in the natural control of HIV-1 infection and for exploring HERV-K(HML-2)-targeted HIV-1 vaccines and immunotherapeutics.