ABSTRACT
Background. Effectively interrupting the source of transmission is a critical step in ending the HIV epidemic. COMEBACK (NCT04519970) is a 48-week single-center study in Chicago implemented in September 2020, with its main objectives to reengage lost-to-care patients and rapidly reinitiate ART to promote VS and favorable PROs. Methods. Adults off ART >=2 weeks, without history of significant B/F/TAF resistance or renal impairment, were rapidly started on B/F/TAF upon reengagement after same day collection of baseline labs and PROs. A retention screening assessment was used to stratify participants into case management (CM) tiers: Minimal, Moderate, or Advanced. An acuity assessment tool was adapted to determine whether participants needed additional support based on retention and VS. Currently, 80 of the expected 100 subjects are enrolled and 55 have reached the 24-week timepoint. Baseline and 6-month endpoints were analyzed for these participants. Results. At baseline (N=55), median age was 34 years (range, 24-62), with 92.6% Black and 72.2% cisgender male. Median CD4+ was 338 cells/mm3, with a median viral load 7,402copies/mL, (range, < 40-333,350, 16.3% VS). Median time off ART was 2.6 months (range, 0.5-243). For CM, participants were stratified into Minimal (71%) and Moderate (29%) tiers;none were identified as Advanced. Table 1 reflects tier shifts through 24 weeks. Shifts inCMintensity differs from the HIV adherence self-efficacy PRO completed within 24 weeks, indicating that at least 50% underestimated their need to integrate and maintain adherence to ART treatment. Forty of 55 participants (72.7%) were retained-in-care at 6 months, with VS in 61.8% (N=34/55) by intention-to-treat and 85% (N=34/40) by observed analysis. No resistance to B/F/TAF was detected through 6 months. Note: The table reflects patients retained on study at their week 24 endpoint. Conclusion. VS was high for participants retained-in-care, but lapses in retention and shifts toward more intense CM were likely due to social determinants of health challenges, including incarceration, housing insecurity, and COVID-19-related disruptions in healthcare.
ABSTRACT
Background. Although studies show most COVID-19 survivors have post-infection immunity against SARS-CoV-2 that could prevent re-infection, there is still a need to identify the breadth of antibody (Ab) responses associated with clinical phenotypes. We characterized Ab profiles at the estimated peak of Ab diversity among adults with recovered SARS-CoV-2 infections and determined their relationships with clinical factors. Methods. From April-June 2020, 41 health system employees with PCRconfirmed symptomatic COVID-19 infection enrolled 8-10 weeks after symptom onset. Symptom questionnaires including baseline demographics, COVID-19 symptoms, disease severity, and disease duration were collected and plasma samples were assayed using a custom Luminex Multiplex platform (Figure 1) to measure the antibody response against 20 COVID-19 related antigens (Figure 2). Differences in Ab profile titers among different groups were tested using nonparametric t test and Benjamini-Hochberg adjustment for multiplicity. Associations were considered significant at FDR< 0.05. Figure 1: Description of the Luminex Serology Assay Figure 2: List of the COVID-19 Related Antigens and Controls Measured Results. Mean age was 48 years (range 27-68), with 51% female, 37% White, 32% Black, 29% Asian, and 17% LatinX. Ab profiles (Figure 3) showed 100% cross-reactivity with related alpha and beta coronavirus, and 95% with SARS-CoV-1. 78% had Abs against SARS-CoV-2 nucleocapsid protein (NCP). However, 29% of patients had no immune response against the four spike protein epitopes. These participants also reported fewer symptoms, including no cases of anosmia/ageusia, suggesting mild illness. Anosmia/ageusia, fever, and cough associated significantly with higher Ab titers (Figure 4). Conclusion. Broad immune responses to various SARS-CoV-2 and related antigens were found among a heterogeneous patient population. However, less than 3 months after symptom onset, protective Ab responses to SARS-CoV-2 spike proteins were not detected in nearly one-third of recovered patients, primarily with mild infection. Intact sense of smell and taste demonstrated the greatest association with loss of seroprotective SARS-CoV-2 Ab responses, which may be clinically useful to predict post-infection immunity. Next steps include comparing the magnitude of Ab responses following full series completion with mRNA vaccination among this cohort.
ABSTRACT
Background Loneliness is a concern among older people living with HIV (PLWH), especially given the ongoing COVID-19 pandemic. Currently, there is little research characterizing loneliness and race. To investigate how HIV impacts older (age 50+) PLWH in the US, a study called Aging with Dignity, Health, Optimism and Community (ADHOC) was launched at ten sites to collect self-reported data. This study uses ADHOC data to compare loneliness between older Black and White PLWH. Methods A cross-sectional analysis was performed to compare loneliness between older Black and White PLWH. Loneliness was assessed using the Three-item Loneliness Scale, a validated patient-reported outcome measure (range 3-9), with higher scores indicating greater loneliness. Student's t-test was used to compare loneliness between White and Black people. Control variables for loneliness were identified a priori and included in a multivariable linear regression model. Results Of 868 participants, the average age was 60 (SD 6.2) years, 77% (N=671) were White and 23% (N=197) were Black, 85% were male, and 82% were gay or lesbian. In bivariate analyses, Black participants were less lonely than White participants (5.2 vs 5.6, P=.02). In the multivariable linear regression analysis, Black participants were again less lonely than Whites (coef. -0.45, P=0.01) while controlling for age, education, depression, anxiety, number of co-morbid conditions, being single, income, gender, sexual orientation, and spirituality (Adjusted R2=0.38;P<.01). Conclusion Among PLWH over age 50 in ADHOC, Black participants experienced less loneliness than White participants, even after controlling for a variety of factors. Additional research is needed to better understand the causes of these racial differences, so that programs designed to decrease loneliness among PLWH can consider the unique characteristics of each group.
ABSTRACT
Background: Patients with underlying medical conditions have a greater risk of developing severe COVID-19. Unlike vaccine-derived immunity which develops over time, administration of neutralizing monoclonal antibodies is an immediate, passive humoral immunotherapy, with the potential to reduce disease progression, emergency room visits, hospitalizations, and death. Methods: In this phase 3 portion of the BLAZE-1 trial, a high-risk ambulatory cohort of 1035 patients with mild-to-moderate COVID-19 were randomly assigned 1:1 to receive a single intravenous infusion of a neutralizing monoclonal antibody combination treatment consisting of 2800mg bamlanivimab+2800mg etesevimab together, or placebo, within 3 days of laboratory diagnosis. The primary outcome was overall patient clinical status, measured by the proportion of patients who experienced COVID-19-related hospitalization or death by any cause by Day 29. Results: 1035 patients were randomized and infused (mean age [SD];53.8 years [16.8], female (52%)). A 70% reduction in COVID-19-related hospitalization and death by any cause by Day 29 was observed in patients who received the bamlanivimab+etesevimab combination treatment (11/518 arm total) compared to those who received placebo (36/517 arm total) (Δ[95% CI]=-4.8[-7.4,-2.3])(p=0.0004). No deaths were observed among patients who received the combination treatment, 10 deaths were reported in the placebo group, at least 8 designated COVID-19-related. A significantly greater reduction in log10(viral load) from baseline at Day 7 was observed amongst patients who received bamlanivimab+etesevimab compared to placebo (Δ[95% CI]=-1.20[-1.46,-0.94])(p<0.00000001). The median time to sustained symptom resolution was shorter for those who received the combination treatment (days [95% CI]=8[7.0,8.0]) compared to those who received placebo (days [95% CI]=9[8.0,10.0])(p=0.007). Similar rates of adverse events were observed between placebo (60/517,11.6%) and combination treatment groups (69/518,13.3%). Conclusion: 2800mg bamlanivimab+2800mg etesevimab neutralizing monoclonal antibody combination therapy significantly reduced COVID-19- related hospitalizations and deaths amongst high-risk ambulatory patients and accelerated the decline in viral load and disease symptoms over time. This study confirms that early intervention with bamlanivimab + etesevimab greatly improves the clinical outcomes for high-risk ambulatory patients, and links reduction in nasopharyngeal viral load to clinically meaningful benefits.
ABSTRACT
Background: Older adults (≥50 y) living with HIV (OALWH) may experience elevated levels of depression, anxiety, and loneliness. Online mindfulness lessons have the potential to ameliorate these problems and enhance access, especially during the COVID-19 pandemic. The objective of this randomized controlled trial was to determine the effectiveness of online mindfulness lessons in reducing feelings of depression, anxiety, and loneliness among OALWH. Methods: The study was conducted between May and August 2020. Individuals with any degree of self-reported loneliness at baseline were eligible to participate. Outcomes of interest included depression, measured using the Center for Epidemiologic Studies Depression Scale (CES-D-10), anxiety measured using the Generalized Anxiety Disorder (GAD-7), and loneliness measured using both the Three-item Loneliness Scale (3IL) and a Daily Diary that asked “How lonely do you feel today?” Two sample t-tests were used to compare group scores at follow-up. Results: Of 214 participants who were randomized, the mean (SD) age was 60.4 (5.9) years, 89% were male, 69% were white, and 74% were gay or lesbian. At the end of the 25-day intervention, the intervention group demonstrated reduced levels of depression (2.6 point improvement;p<0.01), and reduced levels of anxiety (1.5 point improvement;p=0.03) compared to the control group (Table 1). Among the subset of participants with elevated baseline depression scores (defined as CES-D-10 ≥ 8), the between-group improvement in depression scores was greater (4.2 point improvement;p<0.01). Similarly, among the subset of participants with elevated baseline anxiety scores (defined as GAD-7 ≥ 5), the between-group improvement in anxiety scores was greater (2.4 point improvement;p<0.01). Loneliness improved significantly, as indicated by the Daily Diary, for those with at least moderate loneliness at baseline (0.7 point improvement;p<0.01). Conclusion: This randomized controlled trial is the first to show that a series of brief, online mindfulness audio lessons improves mental health outcomes among OALWH who report some degree of loneliness. For many patients, this intervention may offer emotional relief, particularly with regard to depression and anxiety, even in the face of the COVID-19 pandemic.
ABSTRACT
Background: Remdesivir (RDV) has been shown to shorten recovery time and was well tolerated in patients with severe COVID-19. Here we report safety of RDV in patients with moderate COVID-19. Methods: We conducted an open-label, phase 3 trial (NCT04252664) in hospitalized patients with confirmed SARS-CoV-2 infection, evidence of pulmonary infiltrates, and oxygen saturation >94% on room air. Patients were randomly assigned to receive RDV (5 or 10 days) or standard of care (SOC). RDV was dosed intravenously at 200 mg on day 1, 100 mg daily thereafter. Adverse events (AEs) and laboratory abnormalities were evaluated through the day 11 data cut;safety data through day 28 will be presented at the meeting. Results: 584 patients were randomized and treated (5d RDV: n=191;10d RDV, n=193;SOC: n=200). Baseline characteristics were balanced among groups;median (range) age was 57y (12-95y), 39% were female and 19% Black, 39% had arterial hypertension, 15% hyperlipidemia, 11% asthma. Briefly, across both the 5d and 10d arms, RDV was well tolerated with a similar rate of Grade 3 or 4 AEs and fewer SAEs compared to SOC (Table). AEs more common with RDV vs SOC included nausea, headache, and hypokalemia. Overall, across the 3 arms, incidence of AEs leading to discontinuation and death were low and no clinically relevant changes in laboratory parameters were observed. In addition, median changes in renal and liver function tests from baseline were not statistically significant between the RDV 5d and RDV 10d groups compared to the SOC only group at d14 (Table 1). Conclusion: RDV given for 5d or 10d was well tolerated in patients with moderate COVID-19. No clinically significant safety signals were observed with RDV vs SOC. (Figure Presented).