Background

We investigated the effect of HIV on COVID-19 outcomes with attention to selection bias due to differential testing and comorbidity burden.

Methods

This was a retrospective cohort analysis using four hierarchical outcomes: positive SARS-CoV-2 test, COVID-19 hospitalization, intensive care unit (ICU) admission and hospital mortality. The effect of HIV status was assessed using traditional covariate-adjusted, inverse probability-weighted (IPW) analysis based on covariate distributions for testing bias (testing IPWs), HIV infection status (HIV-IPWs) and combined models. Among people living with HIV (PWH), we evaluated whether CD4 count and HIV plasma viral load (pVL) discriminated between those who did and those who did not develop study outcomes using receiver operating characteristic analysis.

Results

Between March and November 2020, 63 319 people were receiving primary care services at the University of California San Diego (UCSD), of whom 4017 were PWH. The PWH had 2.1 times the odds of a positive SARS-CoV-2 test compared with those without HIV after weighting for potential testing bias, comorbidity burden and HIV-IPW [95% confidence interval (CI): 1.6-2.8]. Relative to people without HIV, PWH did not have an increased rate of COVID-19 hospitalization after controlling for comorbidities and testing bias [adjusted incidence rate ratio (aIRR) = 0.5, 95% CI: 0.1-1.4]. PWH did not have a different rate of ICU admission (aIRR = 1.08, 95% CI: 0.31-3.80) or of in-hospital death (aIRR = 0.92, 95% CI: 0.08-10.94) in any examined model. Neither CD4 count nor pVL predicted any of the hierarchical outcomes among PWH.

Conclusions

People living with HIV have a higher risk of COVID-19 diagnosis than those without HIV but the outcomes are similar in both groups.

Abstract: Background: We investigated the effect of HIV on COVID-19 outcomes with attention to selection bias due to differential testing and to comorbidity burden. Methods: Retrospective cohort analysis using four hierarchical outcomes: positive SARS-CoV-2 test, COVID-19 hospitalization, intensive care unit (ICU) admission, and hospital mortality. The effect of HIV status was assessed using traditional covariate-adjusted, inverse probability weighted (IPW) analysis based on covariate distributions for testing bias (testing IPWs), HIV infection status (HIV IPWs), and combined models. Among PWH, we evaluated whether CD4 count and HIV plasma viral load (pVL) discriminated between those who did or did not develop study outcomes using receiver operating characteristic analysis. Results: Between March and November 2020, 63,319 people were receiving primary care services at UCSD, of whom 4,017 were people living with HIV (PWH). PWH had 2.1 times the odds of a positive SARS-CoV-2 test compared to those without HIV after weighting for potential testing bias, comorbidity burden, and HIV-IPW (95% CI 1.6-2.8). Relative to persons without HIV, PWH did not have an increased rate of COVID-19 hospitalization after controlling for comorbidities and testing bias [adjusted incidence rate ratio (aIRR): 0.5, 95% CI: 0.1 – 1.4]. PWH had neither a different rate of ICU admission (aIRR:1.08, 95% CI; 0.31 – 3.80) nor in-hospital death (aIRR:0.92, 95% CI; 0.08 – 10.94) in any examined model. Neither CD4 count nor pVL predicted any of the hierarchical outcomes among PWH. Conclusions: PWH have a higher risk of COVID-19 diagnosis but similar outcomes compared to those without HIV. Summary point: After considering the effects of potential bias due to differential testing, comorbidities, and other patient characteristics, people with HIV had an increased rate of SARS-CoV-2 positivity and similar rates of hospitalization, ICU admission, and death.

Abstract Background HIV-ASSIST is an online, clinical decision support tool that helps HIV clinicians select antiretroviral (ARV) regimens for patients with HIV by accounting for individual patient characteristics. Concordance between HIV-ASSIST recommendations and expert opinion has been reported to be as high as 89% in treatment-experienced patients. We evaluated the utility of the HIV-ASSIST tool for a heavily treatment-experienced, complex patient population at the University of California, San Diego (UCSD) by comparing regimens recommended by HIV-ASSIST with regimens recommended by HIV experts. Methods We identified 14 patients through a routine HIV drug resistance teaching conference at our clinic. Each case was reviewed by 5 HIV clinical experts who independently recommended an ARV regimen. A consensus “best” regimen was agreed upon among the 5 experts for each patient. Consensus regimens were compared for concordance to the top 5 regimens recommended by the HIV-ASSIST tool. HIV-ASSIST regimens were also reviewed to determine if any were high or moderate risk for virologic failure due to patient or resistance characteristics, or drug-drug interactions (DDIs). Results The patients analyzed were medically and psychosocially complex, with a high rate of multi-class resistance (Table 1). Expert-recommended regimens were concordant with one of the top five regimens recommended by the HIV-ASSIST tool for 4/14 (28%) patients (Table 2). We further classified 20/70 (29%) regimens as high risk for virologic failure and 12/70 (17%) regimens as moderate risk for virologic failure (Figure 1). Table 2.Expert-recommended consensus regimens compared to the top 5 HIV-ASSIST regimens for 14 patients with HIV and a history of drug resistance, multimorbidity, and polypharmacy.Figure 1Classification of HIV-ASSIST regimens by HIV clinical experts as either acceptable, moderate risk or high risk for virologic failure. Conclusion Compared to prior reports, we found lower concordance between ART regimens recommended by HIV experts vs those recommended by the HIV-ASSIST tool in patients with HIV drug-resistance and/or complex comorbidities and potential DDIs. Moreover, several HIV-ASSIST regimens were considered at risk for virologic failure. We recommend caution in using the HIV-ASSIST tool for complex patients with significant drug resistance. Disclosures Lucas Hill, PharmD, AAHIVP, Gilead Sciences: Speakers Bureau.

Background

Accurate estimates of HIV incidence are necessary to monitor progress towards Ending the HIV Epidemic (EHE) initiative targets (90% decline by 2030). U.S. incidence estimates are derived from a CD4 depletion model (CD4 model). We performed simulation-based analyses to investigate the ability of this model to estimate HIV incidence when implementing EHE interventions that have the potential to shorten the duration between HIV infection and diagnosis (diagnosis delay).

Methods

Our simulation study evaluates the impact of three parameters on the accuracy of incidence estimates derived from the CD4 model: rate of HIV incidence decline, length of diagnosis delay, and sensitivity of using CD4 + cell counts to identify new infections (recency error). We model HIV incidence and diagnoses after the implementation of a theoretical prevention intervention and compare HIV incidence estimates derived from the CD4 model to simulated incidence.

Results

Theoretical interventions that shortened the diagnosis delay (10-50%) result in overestimation of HIV incidence by the CD4 model (10-92%) in the first year and by more than 10% for the first 6 years after implementation of the intervention. Changes in the rate of HIV incidence decline and the presence of recency error had minimal impact on the accuracy of incidence estimates derived from the CD4 model.

Conclusion

In the setting of EHE interventions to identify persons with HIV earlier during infection, the CD4 model overestimates HIV incidence. Alternative methods to estimate incidence based on objective measures of incidence are needed to assess and monitor EHE interventions.

The present work was undertaken to elucidate the facet-dependent activity of Ag for the electrochemical reduction of CO 2 to CO. To this end, CO 2 reduction was investigated over Ag thin films with (111), (100), and (110) orientations prepared via epitaxial growth on single-crystal Si wafers with the same crystallographic orientations. This preparation technique yielded larger area electrodes than can be achieved using single-crystals, which enabled the electrocatalytic activity of the corresponding Ag surfaces to be quantified in the Tafel regime. The Ag(110) thin films exhibited higher CO evolution activity compared to the Ag(111) and Ag(100) thin films, consistent with previous single-crystal studies. Density functional theory calculations suggest that CO 2 reduction to CO is strongly facet-dependent, and that steps are more active than highly coordinated terraces. This is the result of both a higher binding energy of the key intermediate COOH as well as an enhanced double-layer electric field stabilization over undercoordinated surface atoms located at step edge defects. As a consequence, step edge defects likely dominate the CO 2 reduction activity observed over the Ag(111) and Ag(100) thin films. The higher activity observed over the Ag(110) thin film is then related to the larger density of undercoordinated sites compared to the Ag(111) and Ag(100) thin films. Our conclusion that undercoordinated sites dominate the CO 2 reduction activity observed over close-packed surfaces highlights the need to consider the contribution of such defects in studies of single-crystal electrodes.

Helicobacter pylori infects the human gastric mucosa causing a chronic infection that is the primary risk factor for gastric cancer development. Recent studies demonstrate that H. pylori promotes tolerogenic dendritic cell (DC) development indicating that this bacterium evades the host immune response. However, the signaling pathways involved in modulating DC activation during infection remain unclear. Here, we report that H. pylori infection activated the signal transducer and activator of transcription 3 (STAT3) pathway in murine bone marrow-derived DCs (BMDCs) and splenic DCs isolated ex vivo. Isogenic cagA-, cagE-, vacA- and urease-mutants exhibited levels of phosphoSTAT3 that were comparable to in the wild-type (WT) parent strain. H. pylori-infected BMDCs produced increased immunosuppressive IL-10, which activated STAT3 in an autocrine/paracrine fashion. Neutralization of IL-10 prevented H. pylori-mediated STAT3 activation in both BMDCs and splenic DCs. In addition, anti-IL-10 treatment of infected H. pylori-BMDCs was associated with increased CD86 and MHC II expression and enhanced proinflammatory IL-1β cytokine secretion. Finally, increased CD86 and MHC II expression was detected in H. pylori-infected STAT3 knockout DCs when compared to WT controls. Together, these results demonstrate that H. pylori infection induces IL-10 secretion in DCs, which activates STAT3, thereby modulating DC maturation and reducing IL-1β secretion. These findings identify a host molecular mechanism by which H. pylori can manipulate the innate immune response to potentially favor chronic infection and promote carcinogenesis.

BACKGROUND: High-risk alcohol use is a common surgical risk factor. Stopping or reducing alcohol use in the weeks before and after surgery could improve surgical health and outcomes. The purpose of this study was to evaluate the feasibility and acceptability of 2 interventions that address high-risk alcohol use in the context of surgery. METHODS: Participants included patients scheduled for elective surgeries at an academic health system in the Midwestern United States. Recruitment took place by phone and text. Participants were included if they were 18 to 75 years old, scheduled for elective surgeries, and scored ≥5 on the Alcohol Use Disorders Identification Test-Consumption Tool. Participants were randomized to either a low-intensity intervention, brief advice (10-minute phone-based psychoeducation plus feedback session), or a higher-intensity intervention, health coaching (two 45-minute sessions including education, feedback, motivational interviewing, and goal setting). Assessments took place at baseline and at 1-month and 4-month follow-ups. Alcohol biomarkers were collected the day of surgery. RESULTS: The final study sample included (n = 51) participants randomized to brief advice and health coaching conditions. Participants in both conditions rated interventions as satisfactory and personally relevant. Trial retention was high (86.3%) at 4 months. Attrition was significantly higher in brief advice (n = 6) relative to health coaching (n = 1). Average weekly alcohol use decreased 50% to 60% between baseline and follow-ups in both conditions. Biomarkers corroborated self-report. CONCLUSION: The trial demonstrated intervention feasibility and acceptability. Alcohol use changed in expected directions. The next steps include a randomized controlled trial to test intervention efficacy in reducing alcohol use and surgical complications.

Background

Weight gain and associated metabolic complications are increasingly prevalent among people with HIV (PWH). Glucagon-like peptide-1 receptor agonists (GLP-1RAs) are incretin-based therapies for diabetes and weight management that have been shown to result in substantial weight loss; however, studies of their effects in PWH are limited.

Methods

A retrospective single-center cohort study was conducted among PWH who were taking GLP-1RAs at UC San Diego Owen Clinic between 2/1/2021 to 2/1/2023. Baseline clinical data were collected and changes in weight, body mass index (BMI), and hemoglobin A1C (A1C) before starting GLP-1RAs compared to the most recent clinic visit were calculated (with a minimum of 3 months follow-up time required). Logistic regression was performed to identify variables associated with >5% of total body weight loss.

Results

A total of 225 patients received on average 13 months of GLP-1RA therapy, with 85 (37.8%) achieving the maximum GLP-1RA dose. GLP-1RA therapy resulted, on average, in a loss of 5.4 kg, decrease in BMI by 1.8 kg/m2, and decrease in A1C by 0.6%. In the multivariable analysis, higher baseline BMI [OR 1.10 (1.03-1.16)], treatment duration of GLP-1RA therapy greater than 6 months [OR 3.12 (1.49-6.49], and use of tirzepatide [OR 5.46 (1.44-20.76)] were significantly more likely to be associated with >5% weight loss.

Conclusions

Use of GLP-1RAs led to declines in weight, BMI, and hemoglobin A1C among PWH and offers an additional strategy to address weight gain and diabetes.