Transcriptionally Active Defective HIV-1 Proviruses and Their Association With Immunological Nonresponse to Antiretroviral Therapy.

A subset of antiretroviral therapy-treated persons with human immunodeficiency virus (HIV), referred to as immunological nonresponders (INRs), fails to normalize CD4+ T-cell numbers. In a case-control study involving 26 INRs (CD4 < 250 cells/µL) and 25 immunological responders (IRs; CD4 ≥ 250 cells/µL), we evaluated the potential contribution of transcriptionally competent defective HIV-1 proviruses to poor CD4+ T-cell recovery. Compared to the responders, the INRs had higher levels of cell-associated HIV RNA (P = .034) and higher percentages of HLA-DR+ CD4+ T cells (P < .001). While not encoding replication-competent viruses, the RNA transcripts frequently encoded HIV-1 Gag-p17 and Nef proteins. These transcripts and/or resulting proteins may activate pathway(s) leading to the immunological nonresponse phenotype.

Evaluation of an emergency department-based approach to reduce subsequent opioid overdoses.

Objective: The purpose of this study was to determine the association of a multi-pronged treatment program in emergency department (ED) patients with an acute presentation of opioid use disorder (OUD) on the rate of subsequent opioid overdose (OD). This approach included ED-initiated take-home naloxone, prescription buprenorphine, and an ED-based peer support and recovery program. Methods: This was a retrospective observational analysis of adult patients presenting to the ED at a large urban hospital system from November 1, 2017 to March 17, 2023. Patients with an ED discharge diagnosis of OD or OUD were included. Outcomes determined were subsequent 90-day OD and 180-day OD death. Post hoc analyses were performed to identify intervention utilization throughout the study period including the COVID-19 pandemic as well as ED characteristics associated with subsequent OD and OD death. Statistical comparisons were made using logistic regression and chi-squared test. Results: A total of 2634 patients presented to the ED with an opioid OD or diagnosis of OUD. Subsequent 90-day OD decreased significantly over time (11.5%-2.3%, odds ratio [OR] 0.85, confidence interval [CI] 0.82-0.89). No single intervention was independently associated with 90-day OD or 180-day OD death. Resource utilization was stable during the COVID-19 pandemic and increased afterward. A higher buprenorphine fill-rate among all patients and the Back race subgroup was associated with a decrease in 90-day OD. Conclusions: Subsequent OD and OD death decreased over time after implementation of a multi-pronged treatment program to ED patients with OUD. No single intervention was associated with a decrease of subsequent OD or OD death.