CROI 2024 Abstract eBook

Abstract eBook

Poster Abstracts

categories; the highest effect size was in FA (Z=-5.8,p<0.001 vs -2.1,p=0.035 in PA, and -2.6,p=0.010 in NA). Perceived wellness and hours slept per night increased in all but more relevantly in FA (Z=4.3 and Z=4, both p<0.001). After adjusting by age, sex, and baseline ISI, PHQ9 and adherence to interventions were the only independent factors associated with ISI overtime: compared to NA, ISI decreased in FA (aβ -1.24 [-2.09; -0.38], p=0.005) and showed a trend of reduction in PA (aβ -0.71 [-2.21; 0.78], p=0.349). Conclusion: A real-life outpatient multidimensional management of SQ based on sleep hygiene and individual-tailored interventions proved to be effective in improving SQ and overall wellness in PWH suffering from insomnia. The figure, table, or graphic for this abstract has been removed. Protease Activity in the Lung in HIV-Associated Obstructive Lung Disease (OLD) Chris Wendt 1 , Sarah Samorodnitsky 1 , Monica Kruk 1 , Eric Lock 1 , Alison Morris 2 , Janice Leung 3 , Danielle Weise 1 , Laurie Parker 1 , Pratik Jagtap 1 , Timothy Griffin 1 , Ken Kunisaki 1 1 University of Minnesota, Minneapolis, MN, USA, 2 University of Pittsburgh, Pittsburgh, PA, USA, 3 University of British Columbia, Vancouver, Canada Background: Obstructive lung disease (OLD) is increasingly common among persons with HIV (PWH). The role of proteases in HIV associated OLD is unknown. Methods: We performed mass spectrometry (MS) analysis on endogenous peptides and tandem mass tagging for protein analysis on bronchoalveolar lavage fluid (BALF) samples from PWH with OLD (n=25) and without OLD (n=26) matched on smoking status and ART. We combined untargeted MS and targeted Somascan aptamer-based proteomic approaches to quantify individual proteases and their correlation with lung function. We mapped endogenous peptides to their native proteins that were subjected to protease activity and the accompanying proteases responsible for the peptide cleavages. We used t-tests to compare average FEV1pp between samples in which each cleaved protein was detected versus absent. We accounted for multiple comparisons using a false discovery rate (FDR) adjustment. Using the MEROPS database, we identified candidate proteases for peptide generation by quantifying their affinity to binding sites via z-scores. We assigned proteases as likely responsible for cleavage by the z-scores for each peptide. Results: We identified 27 proteases that correlated with lung function. Proteases associated with low FEV1pp included myeloblastin, kallikrein, cathepsins, metalloproteinases, caspase and neutrophil elastase. Proteases associated with high FEV1pp included carboxypeptidase M, prothrombin, urokinase and gastricin. MS analysis of endogenous peptides identified 1402 proteins that mapped to these peptides, 28 of which were observed in individuals with significantly (FDR <= 0.1) lower average FEV1pp. The top five protease targeted proteins included: alpha-enolase, gelsolin, histone H4, tubulin beta-4B chain and histone H2B type 2-F. Pathway analysis revealed these proteins were associated with gene regulation and included SUMOylation, methylate and demethylate histones, and nucleosomes. The top five proteases demonstrating activity included: neutrophil elastase, granzyme M, cathepsin D, proteinase 3, and cathepsin E (Fig. 1). Conclusion: Like COPD unrelated to HIV, BALF protease abundance and activity is higher in individuals with HIV-associated OLD. We found that proteins involved in gene regulation are susceptible to these proteases as potential therapeutic targets.

1:20 by age, sex, and race/ethnicity. Sleep apnea diagnoses were identified by ICD codes in electronic health records. Using Poisson regression, incident sleep apnea was compared between PWH and PWoH, overall and with PWH stratified by HIV treatment status. Optimal HIV treatment was defined as being on ART (≥1 ART prescription fill), with undetectable HIV RNA (<200 copies/ml), and without immunosuppression (CD4 count ≥500 cells/µl). Next, both HIV-specific and general (non-HIV-specific) risk factors were evaluated. All models included the following covariates: age, sex, race/ethnicity, body mass index, smoking status, substance use, depression, anxiety, cardiovascular disease, diabetes, cerebrovascular disease, cognitive impairment, and number of outpatient visits in the year before baseline. HIV-specific models also included ART use, HIV RNA level, and CD4 count. Results: The study included 11,568 PWH and 225,097 PWoH (for PWH: mean baseline age 48 years, 90% men, 48% White, 20% Hispanic, 17% Black, 7% Asian, 8% Other/unknown race/ethnicity; 93% on ART). During follow-up, 820 PWH and 19,058 of PWoH were diagnosed with sleep apnea. Sleep apnea incidence was significantly lower in PWH (vs. PWoH, adjusted incidence rate ratio [aIRR] = 0.90, 0.84-0.97). Notably, in analyses with PWH stratified by treatment status, lower incidence was observed in sub-optimally treated PWH (vs. PWoH, aIRR = 0.79, 0.70-0.89) but not in optimally treated PWH (vs. PWoH, aIRR = 0.97, 0.89-1.06). Among PWH, incidence was lower in PWH with lower CD4 (vs. PWH with CD4 ≥500 cells/µl: CD4 200-499, aIRR = 0.89, 0.75-1.05; CD4 <200, aIRR = 0.58, 0.35-0.99) or with higher viral load (vs. PWH with HIV RNA <200 copies/ml: HIV RNA ≥10,000, aIRR = 0.59, 0.29-1.19). The associations of general risk factors with sleep apnea were similar by HIV status (data not shown). Conclusion: Sleep apnea risk is independent of HIV status. Lower overall incidence of sleep apnea among PWH may reflect under-diagnosis in PWH with untreated or uncontrolled HIV infection. Outcome of a Multidimensional Intervention for Insomnia in a Cohort of People Living With HIV Maria Mazzitelli 1 , Mattia Trunfio 2 , Lolita Sasset 1 , Davide Leoni 1 , Vincenzo Scaglione 1 , Mauro Marini 1 , Gianluca Gasparini 1 , Angela Favaro 3 , Annamaria Cattelan 1 1 Azienda Ospedaliera di Padova, Padua, Italy, 2 University of California San Diego, La Jolla, CA, USA, 3 University of Padova, Padova, Italy Background: No studies specifically assessed interventions for improving sleep quality (SQ) in people with HIV (PWH). We introduced a multidimensional program for SQ in the routine management at our outpatient clinic and assessed its impact on PWH suffering from insomnia. Methods: Interventional study in adult PWH with subthreshold (≥8), moderate (≥15), or severe (≥22) insomnia at the Insomnia Severity Index (ISI).Participants received sleep hygiene counseling and underwent tailored interventions as shown in the study flow. Based on compliance with prescribed interventions, participants were classified as fully, partial (at least 1 intervention attended when more than one prescribed), and non-adherent (FA-PA-NA). SQ, depression (PHQ9), and well-being were assessed at baseline and after 6 months from the beginning of any interventions. The impact of interventions on insomnia was assessed by mixed-effects models for repeated measures and paired tests for longitudinal data (Wilcoxon, Friedman). Results: Among 730 PWH screened, 277 had altered ISI score, and 175 eventually participated (Fig1A). 65.7% were male, median age and CD4+ T cell count were 51 years and 650 cell/µL, 95.4% PWH had HIV-RNA<50 cp/ mL. 94.8%, 91.0% and 2.8% of participants were referred to psychologist, psychiatrist, and neurologist, and 30.3% and 20.5% had indication to hypo inducing drugs/antidepressants and psychotherapy/cognitive-behavioral therapy. Seventy-seven participants (44.0%) were NA, 16 (9.1%) PA, and 82 (46.8%) FA, with no relevant baseline differences detected in demographics and clinical parameters among them. Baseline ISI categories and their trajectory over time had an improvement in ISI score and in the distribution of insomnia

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CROI 2024 252