Comparing Safety and Effectiveness of Antiretroviral Therapy in a Diverse Population of Older People With HIV.

Background Advances in antiretroviral therapy (ART) enable people with HIV to live longer, healthier lives. However, older people with HIV (OPWH) are more susceptible to long-term toxicity and drug interactions associated with ART. Racial and ethnic minorities have specific social determinants of health, which increase their risks of negative outcomes. Objective To determine if there were differences in the safety and effectiveness of ART in White, Black, and Hispanic OPWH. Methods A retrospective observational study was conducted on patients receiving care between January 1, 2017, and December 31, 2022, at two affiliated HIV clinics in South Florida. The primary effectiveness endpoint was the percentage of OPWH with undetectable viral load (< 50 copies/mL) throughout the study. Secondary safety endpoints were changes in median metabolic, hepatic, and renal parameters. A two-way analysis of variance or the Chi-square test was used to determine differences between groups. Results A total of 116 White, 42 Black, and 40 Hispanic OPWH were included. Upon enrollment, most patients (90.7%) were receiving ART. Of these, the percentage with undetectable viral load was lower among Black (61.8%) compared with White (85.8%; P < 0.01) or Hispanic (83.3%; P < 0.05) patients. Similarly, throughout the study after the first visit, the percentage with undetectable viral load was lower among Black (61.6%) compared with White (84.7%; P < 0.05) or Hispanic (83.3%; P = 0.12) patients. However, there were no significant differences in the percentage of virally suppressed (< 200 copies/mL) participants throughout the study after the first visit between Black (88.5%), White (94.9%), and Hispanic (96.7%) patients. Additionally, no significant changes in safety endpoints were observed among the groups throughout the study. Conclusion Fewer Black OPWH had undetectable viral load upon enrollment and throughout the study compared with White or Hispanic OPWH, suggesting the need to provide more targeted interventions for Black patients.

An alternatively spliced, non-signaling insulin receptor modulates insulin sensitivity via insulin peptide sequestration in C. elegans.

In the nematode C. elegans, insulin signaling regulates development and aging in response to the secretion of numerous insulin peptides. Here, we describe a novel, non-signaling isoform of the nematode insulin receptor (IR), DAF-2B, that modulates insulin signaling by sequestration of insulin peptides. DAF-2B arises via alternative splicing and retains the extracellular ligand binding domain but lacks the intracellular signaling domain. A daf-2b splicing reporter revealed active regulation of this transcript through development, particularly in the dauer larva, a diapause stage associated with longevity. CRISPR knock-in of mScarlet into the daf-2b genomic locus confirmed that DAF-2B is expressed in vivo and is likely secreted. Genetic studies indicate that DAF-2B influences dauer entry, dauer recovery and adult lifespan by altering insulin sensitivity according to the prevailing insulin milieu. Thus, in C. elegans alternative splicing at the daf-2 locus generates a truncated IR that fine-tunes insulin signaling in response to the environment.