SARS-CoV-2 Neutralizing Antibody LY-CoV555 in Outpatients with Covid-19.

BACKGROUND: Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) causes coronavirus disease 2019 (Covid-19), which is most frequently mild yet can be severe and life-threatening. Virus-neutralizing monoclonal antibodies are predicted to reduce viral load, ameliorate symptoms, and prevent hospitalization. METHODS: In this ongoing phase 2 trial involving outpatients with recently diagnosed mild or moderate Covid-19, we randomly assigned 452 patients to receive a single intravenous infusion of neutralizing antibody LY-CoV555 in one of three doses (700 mg, 2800 mg, or 7000 mg) or placebo and evaluated the quantitative virologic end points and clinical outcomes. The primary outcome was the change from baseline in the viral load at day 11. The results of a preplanned interim analysis as of September 5, 2020, are reported here. RESULTS: At the time of the interim analysis, the observed mean decrease from baseline in the log viral load for the entire population was -3.81, for an elimination of more than 99.97% of viral RNA. For patients who received the 2800-mg dose of LY-CoV555, the difference from placebo in the decrease from baseline was -0.53 (95% confidence interval [CI], -0.98 to -0.08; P = 0.02), for a viral load that was lower by a factor of 3.4. Smaller differences from placebo in the change from baseline were observed among the patients who received the 700-mg dose (-0.20; 95% CI, -0.66 to 0.25; P = 0.38) or the 7000-mg dose (0.09; 95% CI, -0.37 to 0.55; P = 0.70). On days 2 to 6, the patients who received LY-CoV555 had a slightly lower severity of symptoms than those who received placebo. The percentage of patients who had a Covid-19-related hospitalization or visit to an emergency department was 1.6% in the LY-CoV555 group and 6.3% in the placebo group. CONCLUSIONS: In this interim analysis of a phase 2 trial, one of three doses of neutralizing antibody LY-CoV555 appeared to accelerate the natural decline in viral load over time, whereas the other doses had not by day 11. (Funded by Eli Lilly; BLAZE-1 ClinicalTrials.gov number, NCT04427501.).

Pneumocystis jirovecii in solid organ transplant recipients: updates in epidemiology, diagnosis, treatment, and prevention.

PURPOSE OF REVIEW: This review highlights the epidemiology of Pneumocystis jirovecii pneumonia in solid organ transplant recipients, advancements in the diagnostic landscape, and updates in treatment and prevention. RECENT FINDINGS: The increasing use of immune-depleting agents in the context of solid organ transplantation has given rise to P. jirovecii pneumonia in this population. The use of prophylaxis has dramatically reduced risk of infection; however, late-onset infections occur after cessation of prophylaxis and in the setting of lymphopenia, advancing patient age, acute allograft rejection, and cytomegalovirus infection. Diagnosis requires respiratory specimens, with PCR detection of Pneumocystis replacing traditional staining methods. Quantitative PCR may be a useful adjunct to differentiate between infection and colonization. Metagenomic next-generation sequencing is gaining attention as a noninvasive diagnostic tool. Trimethoprim-sulfamethoxazole remains the drug of choice for treatment and prevention of Pneumocystis pneumonia. Novel antifungal agents are under investigation. SUMMARY: P. jirovecii is a fungal opportunistic pathogen that remains a cause of significant morbidity and mortality in solid organ transplant recipients. Early detection and timely treatment remain the pillars of management.

Complementing the United States Household Food Security Survey Module with Items Reflecting Social Unacceptability.

BACKGROUND: Social unacceptability of food access is part of the lived experience of food insecurity but is not assessed as part of the United States Household Food Security Survey Module (HFSSM). OBJECTIVES: The objectives were as follows: 1) to determine the psychometric properties of 2 additional items on social unacceptability in relation to the HFSSM items and 2) to test whether these 2 items provided added predictive accuracy to that of the HFSSM items for mental health outcomes. METHODS: Cross-sectional data used were from the Intersection of Material-Need Insecurities and HIV and Cardiovascular Health substudy of the Multicenter AIDS Cohort Study/Women's Interagency HIV Study Combined Cohort Study. Data on the 10-item HFSSM and 2 new items reflecting social unacceptability were collected between Fall 2020 and Fall 2021 from 1342 participants from 10 United States cities. The 2 social unacceptability items were examined psychometrically in relation to the HFSSM-10 items using models from item response theory. Linear and logistic regression was used to examine prediction of mental health measured by the 20-item Center for Epidemiologic Studies Depression scale and the 10-item Perceived Stress Scale. RESULTS: The social unacceptability items were affirmed throughout the range of severity of food insecurity but with increasing frequency at higher severity of food insecurity. From item response theory models, the subconstructs reflected in the HFSSM-10 and the subconstruct of social unacceptability were distinct, not falling into one dimension. Regression models confirmed that social unacceptability was distinct from the subconstructs reflected in the HFSSM-10. The social unacceptability items as a separate scale explained more (∼1%) variation in mental health than when combined with the HFSSM-10 items in a single scale, and the social unacceptability subconstruct explained more (∼1%) variation in mental health not explained by the HFSSM-10. CONCLUSIONS: Two social unacceptability items used as a separate scale along with the HFSSM-10 predicted mental health more accurately than did the HFSSM-10 alone.

Disrupting the Path from Depression to Loneliness: Multilevel Resilience among Older Sexual Minority Men with and without HIV.

Existing studies examining resilience among sexual minority men (SMM) have been limited by only analyzing 1 level of resilience. We therefore investigated the impact of multiple levels of resilience on the bidirectional relationship between loneliness and depression symptoms among older SMM. Loneliness, depression symptoms, and multilevel resilience scores were collected across 3 time points (October 2016 to March 2017 [T1]; October 2017 to March 2018 [T2]; and October 2018 to March 2019 [T3]) among 1,264 SMM aged 40 years and older living with and without HIV. Longitudinal mediation models were used to test the mediating effect of the multilevel resilience factors at T2 on the bidirectional relationship between loneliness and depression symptoms, adjusting for sociodemographic covariates. The multilevel resilience factors were negatively associated with loneliness and depression symptoms at T1. The individual-level global resilience factor was associated with decreased odds of depression symptoms (odds ratio [OR] = 0.50; 95% CI, 0.32-0.78), while the interpersonal-level relationship confidence (OR = 0.43; 95% CI, 0.24-0.77) and reliability (OR = 0.36; 95% CI, 0.15-0.84) factors were associated with decreased odds of loneliness at T3. The total effect of loneliness at T1 on depressive symptoms at T3 was ß = 0.20 (95% CI, 0.11-0.28) and was reduced to ß = 0.08 (95% CI, -0.04 to 0.20) after the inclusion of the multilevel resilience factors. The total effect of depressive symptoms at T1 on loneliness at T3 was similar (ß = 0.21; 95% CI, 0.13-0.28) with the direct effect of ß = 0.01 (95% CI, -0.08 to 0.11) after the inclusion of the multilevel resilience factors. Regarding specific indirect effects, individual-level global resilience (depression symptoms at T3 only) as well as the interpersonal-level relationship reliability and confidence (loneliness at T3 model only) factors were statistically significant. Multilevel resilience factors mediated the bidirectional relationship between loneliness and depression symptoms. Mental health interventions should consider implementing resilience-informed strategies that mitigate depression symptoms and loneliness among older SMM.

RESUMEN: Los estudios existentes que examinan la resiliencia entre los hombres de minorías sexuales (HSH) se han visto limitados por analizar sólo 1 nivel de resiliencia. Por lo tanto, investigamos el impacto de múltiples niveles de resiliencia en la relación bidireccional entre la soledad y los síntomas de depresión entre los hombres mayores de minorías sexuales. Se recopilaron datos sobre soledad, síntomas de depresión y resiliencia multinivel a lo largo de 3 puntos temporales (octubre de 2016 a marzo de 2017 [T1]; octubre de 2017 a marzo de 2018 [T2]; y octubre de 2018 a marzo de 2019 [T3]) entre 1,264 SMM de 40 años o más que viven con y sin VIH. Se utilizaron modelos de mediación longitudinal para probar el efecto mediador de los factores de resiliencia multinivel en T2 sobre la relación bidireccional entre la soledad y los síntomas de depresión, ajustando por covariables sociodemográficas. Los factores de resiliencia multinivel se asociaron negativamente con la soledad y los síntomas de depresión en T1. El factor de resiliencia global a nivel individual se asoció con menores probabilidades de síntomas de depresión (odds ratio [OR] = 0,50; IC 95%, 0,32 − 0,78), mientras que el factor de confianza en las relaciones a nivel interpersonal (OR = 0.43; 95% CI, 0.24­0.77) y los factores de fiabilidad (OR = 0.36; 95% CI, 0.15­0.84) se asociaron con menores probabilidades de soledad en T3. El efecto total de la soledad en T1 sobre los síntomas depresivos en T3 fue ß = 0.20 (95% CI, 0.11­0.28) y se redujo a ß = 0.08 (95% CI, -0.04 to 0.20) tras la inclusión de los factores de resiliencia multinivel. El efecto total de los síntomas depresivos en T1 sobre la soledad en T3 fue similar (ß = 0.21; 95% CI, 0.13­0.28) con el efecto directo de ß = 0.01 (95% CI, -0.08 to 0.11) tras la inclusión de los factores de resiliencia multinivel. En cuanto a los efectos indirectos específicos, los factores de resiliencia global a nivel individual (síntomas de depresión sólo en T3) así como la fiabilidad y confianza de las relaciones interpersonales (soledad en el modelo T3 solamente) fueron estadísticamente significativos. Los factores de resiliencia multinivel mediaron la relación bidireccional entre la soledad y los síntomas de depresión. Las intervenciones de salud mental deberían considerar la implementación de estrategias basadas en la resiliencia que mitiguen los síntomas de la depresión y la soledad entre los SMM mayores.

HIV-Positive Liver Transplant Does not Alter the Latent Viral Reservoir in Recipients With Antiretroviral Therapy-Suppressed HIV.

The latent viral reservoir (LVR) remains a major barrier to HIV-1 curative strategies. It is unknown whether receiving a liver transplant from a donor with HIV might lead to an increase in the LVR because the liver is a large lymphoid organ. We found no differences in intact provirus, defective provirus, or the ratio of intact to defective provirus between recipients with ART-suppressed HIV who received a liver from a donor with (n = 19) or without HIV (n = 10). All measures remained stable from baseline by 1 year posttransplant. These data demonstrate that the LVR is stable after liver transplantation in people with HIV. Clinical Trials Registration. NCT02602262 and NCT03734393.

Grit is associated with psychological health among older sexual minority men.

Objectives: Studies have shown that grit-defined as perseverance and passion for achieving one's long-term goals-is associated with improved health outcomes, including lower levels of psychological distress. However, the psychometric properties of the original Grit Scale (Grit-O Scale) has not been validated among sexual minority men (SMM). The present study aimed to validate the Grit-O Scale among a sample of older SMM and assess the relationships between the Grit-O Scale factors and symptoms of psychological distress.Method: We used data from a single visit of participants in the Multicenter AIDS Cohort Study (MACS) Healthy Aging longitudinal study. The sample included 981 older SMM (mean age = 61, SD = 8.5) with and without HIV. We conducted confirmatory factor analysis (CFA) to identify the two factors of the Grit-O Scale: consistency of interest and perseverance of effort. We also conducted a latent profile analysis (LPA) to identify distinct profiles of psychological distress from self-reported scales of depression, anxiety, and perceived stress.Results:The Grit-O Scale showed acceptable reliability estimates for the items with Cronbach's alpha reliability coefficients ranging from 0.77 to 0.82. The CFA identified the two factors of the Grit-O Scale with acceptable model fit (root mean square error of approximation = 0.058 [95% CI = 0.050, 0.067], comparative fit index = 0.95, Tucker-Lewis Index = 0.93, standardized root mean square residual = 0.07). The LPA yielded three mutually exclusive profiles of psychological distress (profile 1: low stress, anxiety, and depression; profile 2: high stress and depression and low anxiety; and profile 3: high stress, anxiety, and depression). In adjusted multinominal logistic regression analysis, we found that both higher levels of consistency of interest and perseverance of effort factors of the Grit-O Scale were significantly associated with decreased odds of being in profiles 2 and 3 compared with being in profile 1.Conclusion: Our findings support the use of the Grit-O Scale among older SMM. Grit factors could explain variability in the negative psychological symptoms among older SMM and warrant further investigation.Supplemental data for this article is available online at http://dx.doi.org/10.1080/13607863.2022.2032594.

Real-World Experience of Bamlanivimab for Coronavirus Disease 2019 (COVID-19): A Case-Control Study.

BACKGROUND: Coronavirus disease 2019 (COVID-19) has strained healthcare systems with patient hospitalizations and deaths. Anti-spike monoclonal antibodies, including bamlanivimab, have demonstrated reduction in hospitalization rates in clinical trials, yet real-world evidence is lacking. METHODS: We conducted a retrospective case-control study across a single healthcare system of nonhospitalized patients, age 18 years or older, with documented positive severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) testing, risk factors for severe COVID-19, and referrals for bamlanivimab via emergency use authorization. Cases were defined as patients who received bamlanivimab; contemporary controls had a referral order placed but did not receive bamlanivimab. The primary outcome was 30-day hospitalization rate from initial positive SARS-CoV-2 polymerase chain reaction (PCR). Descriptive statistics, including χ 2 and Mann-Whitney U test, were performed. Multivariable logistic regression was used for adjusted analysis to evaluate independent associations with 30-day hospitalization. RESULTS: Between 30 November 2020 and 19 January 2021, 218 patients received bamlanivimab (cases), and 185 were referred but did not receive drug (controls). Thirty-day hospitalization rate was significantly lower among patients who received bamlanivimab (7.3% vs 20.0%, risk ratio [RR] 0.37, 95% confidence interval [CI]: .21-.64, P < .001), and the number needed to treat was 8. On logistic regression, odds of hospitalization were increased in patients not receiving bamlanivimab and with a higher number of pre-specified comorbidities (odds ratio [OR] 4.19 ,95% CI: 1.31-2.16, P < .001; OR 1.68, 95% CI: 2.12-8.30, P < .001, respectively). CONCLUSIONS: Ambulatory patients with COVID-19 who received bamlanivimab had a lower 30-day hospitalization than control patients in real-world experience. We identified receipt of bamlanivimab and fewer comorbidities as protective factors against hospitalization.Bamlanivimab's role in preventing hospitalization associated with coronavirus disease 2019 (COVID-19) remains unclear. In a real-world, retrospective study of 403 high-risk, ambulatory patients with COVID-19, receipt of bamlanivimab compared to no monoclonal antibody therapy was associated with lower 30-day hospitalization.

National Landscape of Human Immunodeficiency Virus-Positive Deceased Organ Donors in the United States.

BACKGROUND: Organ transplantation from donors with human immunodeficiency virus (HIV) to recipients with HIV (HIV D+/R+) presents risks of donor-derived infections. Understanding clinical, immunologic, and virologic characteristics of HIV-positive donors is critical for safety. METHODS: We performed a prospective study of donors with HIV-positive and HIV false-positive (FP) test results within the HIV Organ Policy Equity (HOPE) Act in Action studies of HIV D+/R+ transplantation (ClinicalTrials.gov NCT02602262, NCT03500315, and NCT03734393). We compared clinical characteristics in HIV-positive versus FP donors. We measured CD4 T cells, HIV viral load (VL), drug resistance mutations (DRMs), coreceptor tropism, and serum antiretroviral therapy (ART) detection, using mass spectrometry in HIV-positive donors. RESULTS: Between March 2016 and March 2020, 92 donors (58 HIV positive, 34 FP), representing 98.9% of all US HOPE donors during this period, donated 177 organs (131 kidneys and 46 livers). Each year the number of donors increased. The prevalence of hepatitis B (16% vs 0%), syphilis (16% vs 0%), and cytomegalovirus (CMV; 91% vs 58%) was higher in HIV-positive versus FP donors; the prevalences of hepatitis C viremia were similar (2% vs 6%). Most HIV-positive donors (71%) had a known HIV diagnosis, of whom 90% were prescribed ART and 68% had a VL <400 copies/mL. The median CD4 T-cell count (interquartile range) was 194/µL (77-331/µL), and the median CD4 T-cell percentage was 27.0% (16.8%-36.1%). Major HIV DRMs were detected in 42%, including nonnucleoside reverse-transcriptase inhibitors (33%), integrase strand transfer inhibitors (4%), and multiclass (13%). Serum ART was detected in 46% and matched ART by history. CONCLUSION: The use of HIV-positive donor organs is increasing. HIV DRMs are common, yet resistance that would compromise integrase strand transfer inhibitor-based regimens is rare, which is reassuring regarding safety.

HOPE in action: A prospective multicenter pilot study of liver transplantation from donors with HIV to recipients with HIV.

Liver transplantation (LT) from donors-with-HIV to recipients-with-HIV (HIV D+/R+) is permitted under the HOPE Act. There are only three international single-case reports of HIV D+/R+ LT, each with limited follow-up. We performed a prospective multicenter pilot study comparing HIV D+/R+ to donors-without-HIV to recipients-with-HIV (HIV D-/R+) LT. We quantified patient survival, graft survival, rejection, serious adverse events (SAEs), human immunodeficiency virus (HIV) breakthrough, infections, and malignancies, using Cox and negative binomial regression with inverse probability of treatment weighting. Between March 2016-July 2019, there were 45 LTs (8 simultaneous liver-kidney) at 9 centers: 24 HIV D+/R+, 21 HIV D-/R+ (10 D- were false-positive). The median follow-up time was 23 months. Median recipient CD4 was 287 cells/µL with 100% on antiretroviral therapy; 56% were hepatitis C virus (HCV)-seropositive, 13% HCV-viremic. Weighted 1-year survival was 83.3% versus 100.0% in D+ versus D- groups (p = .04). There were no differences in one-year graft survival (96.0% vs. 100.0%), rejection (10.8% vs. 18.2%), HIV breakthrough (8% vs. 10%), or SAEs (all p > .05). HIV D+/R+ had more opportunistic infections, infectious hospitalizations, and cancer. In this multicenter pilot study of HIV D+/R+ LT, patient and graft survival were better than historical cohorts, however, a potential increase in infections and cancer merits further investigation.

Disparities in COVID-19 Monoclonal Antibody Delivery: a Retrospective Cohort Study.

BACKGROUND: Disparities in access to anti-SARS-CoV-2 monoclonal antibodies have not been well characterized. OBJECTIVE: We sought to explore the impact of race/ethnicity as a social construct on monoclonal antibody delivery. DESIGN/PATIENTS: Following implementation of a centralized infusion program at a large academic healthcare system, we reviewed a random sample of high-risk ambulatory adult patients with COVID-19 referred for monoclonal antibody therapy. MAIN MEASURES: We examined the relationship between treatment delivery, race/ethnicity, and other demographics using descriptive statistics, binary logistic regression, and spatial analysis. KEY RESULTS: There was no significant difference in racial composition between patients who did (n = 25) and patients who did not (n = 378) decline treatment (p = 0.638). Of patients who did not decline treatment, 64.8% identified as White, 14.8% as Hispanic/Latinx, and 11.1% as Black. Only 44.6% of Hispanic/Latinx and 31.0% of Black patients received treatment compared to 64.1% of White patients (OR 0.45, 95% CI 0.25-0.81, p = 0.008, and OR 0.25, 95% CI 0.12-0.50, p < 0.001, respectively). In multivariable analysis including age, race, insurance status, non-English primary language, county Social Vulnerability Index, illness severity, and total number of comorbidities, associations between receiving treatment and Hispanic/Latinx or Black race were no longer statistically significant (AOR 1.32, 95% CI 0.69-2.53, p = 0.400, and AOR 1.34, 95% CI 0.64-2.80, p = 0.439, respectively). However, patients who were uninsured or whose primary language was not English were less likely to receive treatment (AOR 0.16, 95% CI 0.03-0.88, p = 0.035, and AOR 0.37, 95% CI 0.15-0.90, p = 0.028, respectively). Spatial analysis suggested decreased monoclonal antibody delivery to Cook County patients residing in socially vulnerable communities. CONCLUSIONS: High-risk ambulatory patients with COVID-19 who identified as Hispanic/Latinx or Black were less likely to receive monoclonal antibody therapy in univariate analysis, a finding not explained by patient refusal. Multivariable and spatial analyses suggested insurance status, language, and social vulnerability contributed to racial disparities.

Biopsychosocial Health Outcomes and Experienced Intersectional Stigma in a Mixed HIV Serostatus Longitudinal Cohort of Aging Sexual Minority Men, United States, 2008‒2019.

Objectives. To determine whether intersectional stigma is longitudinally associated with biopsychosocial outcomes. Methods. We measured experienced intersectional stigma (EIS; ≥ 2 identity-related attributions) among sexual minority men (SMM) in the United States participating in the Multicenter AIDS Cohort Study. We assessed longitudinal associations between EIS (2008‒2009) and concurrent and future hypertension, diabetes, dyslipidemia, antiretroviral therapy adherence, HIV viremia, health care underutilization, and depression symptoms (2008‒2019). We conducted causal mediation to assess the contribution of intersectional stigma to the relationship between self-identified Black race and persistently uncontrolled outcomes. Results. The mean age (n = 1806) was 51.8 years (range = 22-84 years). Of participants, 23.1% self-identified as Black; 48.3% were living with HIV. Participants reporting EIS (30.8%) had higher odds of hypertension, dyslipidemia, diabetes, depression symptoms, health care underutilization, and suboptimal antiretroviral therapy adherence compared with participants who did not report EIS. EIS mediated the relationship between self-identified Black race and uncontrolled outcomes. Conclusions. Our findings demonstrate that EIS is a durable driver of biopsychosocial health outcomes over the life course. Public Health Implications. There is a critical need for interventions to reduce intersectional stigma, help SMM cope with intersectional stigma, and enact policies protecting minoritized people from discriminatory acts. (Am J Public Health. 2022;112(S4):S452-S462. https://doi.org/10.2105/AJPH.2022.306735).

Effect of Ventricular Assist Device Self-care Simulation-Based Mastery Learning on Driveline Exit Site Infections: A Pilot Study.

BACKGROUND: Ventricular assist device simulation-based mastery learning (SBML) results in better patient and caregiver self-care skills compared with usual training. OBJECTIVE: The aim of this study was to evaluate the effect of SBML on driveline exit site infections. METHODS: We compared the probability of remaining infection free at 3 and 12 months between patients randomized to SBML or usual training. RESULTS: The SBML-training group had no infections at 3 months and 2 infections at 12 months, yielding a Kaplan-Meier estimate of the probability of remaining infection free of 0.857 (95% confidence interval [CI], 0.692-1.00) at 12 months. The usual-training group had 6 infections at 3 months with no additional infections by 12 months. Kaplan-Meier estimates of remaining infection free at 3 and 12 months were 0.878 (95% CI, 0.758-1.00) and 0.748 (95% CI, 0.591-0.946), respectively. Time-to-infection distributions for SBML versus usual training showed a difference in 12-month infection rates of 0.109 (P = .07). CONCLUSIONS: Ventricular assist device self-care SBML resulted in fewer 12-month infections.

Serological Responses to Toxoplasma gondii and Matrix Antigen 1 Predict the Risk of Subsequent Toxoplasmic Encephalitis in People Living With Human Immunodeficiency Virus (HIV).

BACKGROUND: Clinically useful predictors for fatal toxoplasmosis are lacking. We investigated the value of serological assays for antibodies to whole Toxoplasma antigens and to peptide antigens of the Toxoplasma cyst matrix antigen 1 (MAG1), for predicting incident toxoplasmic encephalitis (TE) in people living with human immunodeficiency virus (HIV; PLWH). METHODS: We performed a nested case control study, conducted within the Multicenter AIDS Cohort Study (MACS), using serum samples obtained 2 years prior to diagnosis of TE from 28 cases, and 37 HIV disease-matched Toxoplasma seropositive controls at matched time-points. Sera were tested for Toxoplasma antibodies using a commercial assay and for antibodies to MAG1_4.2 and MAG1_5.2 peptides in enzyme-linked immunosorbent assay (ELISA). RESULTS: Two years prior to clinical diagnosis, 68% of TE cases were MAG1_4.2 seropositive compared with 16% of controls (odds ratio [OR] 25.0, 95% confidence interval [CI] 3.14-199.18). Corresponding results for MAG1_5.2 seropositivity were 36% and 14% (OR 3.6, 95% CI .95-13.42). Higher levels of antibody to MAG1_4.2 (OR 18.5 per doubling of the optical density [OD] value, 95% CI 1.41-242) and to Toxoplasma (OR 2.91 for each OD unit increase, 95% CI 1.48-5.72) were also associated with the risk of TE. When seropositivity was defined as the presence of MAG1 antibody or relatively high levels of Toxoplasma antibody, the sensitivity was 89% and specificity was 68% for subsequent TE. CONCLUSIONS: Antibodies to MAG1 showed predictive value on the occurrence of TE in PLWH, and the predictive performance was further improved by adding the levels of Toxoplasma antibody. These measures could be clinically useful for predicting subsequent diseases in multiple at-risk populations.

A prospective multicenter pilot study of HIV-positive deceased donor to HIV-positive recipient kidney transplantation: HOPE in action.

HIV-positive donor to HIV-positive recipient (HIV D+/R+) transplantation is permitted in the United States under the HIV Organ Policy Equity Act. To explore safety and the risk attributable to an HIV+ donor, we performed a prospective multicenter pilot study comparing HIV D+/R+ vs HIV-negative donor to HIV+ recipient (HIV D-/R+) kidney transplantation (KT). From 3/2016 to 7/2019 at 14 centers, there were 75 HIV+ KTs: 25 D+ and 50 D- (22 recipients from D- with false positive HIV tests). Median follow-up was 1.7 years. There were no deaths nor differences in 1-year graft survival (91% D+ vs 92% D-, P = .9), 1-year mean estimated glomerular filtration rate (63 mL/min D+ vs 57 mL/min D-, P = .31), HIV breakthrough (4% D+ vs 6% D-, P > .99), infectious hospitalizations (28% vs 26%, P = .85), or opportunistic infections (16% vs 12%, P = .72). One-year rejection was higher for D+ recipients (50% vs 29%, HR: 1.83, 95% CI 0.84-3.95, P = .13) but did not reach statistical significance; rejection was lower with lymphocyte-depleting induction (21% vs 44%, HR: 0.33, 95% CI 0.21-0.87, P = .03). In this multicenter pilot study directly comparing HIV D+/R+ with HIV D-/R+ KT, overall transplant and HIV outcomes were excellent; a trend toward higher rejection with D+ raises concerns that merit further investigation.

Donor-derived renal allograft mucormycosis in a combined liver and kidney transplantation: Case report and review of the literature.

Mucormycosis infrequently may present with isolated renal involvement. Among solid organ transplant recipients, renal allograft mucormycosis has been most often associated with medical tourism or transplantation outside of the western world. We report a case of an HIV/HCV co-infected woman who underwent simultaneous liver and kidney transplantation with a Public Health Service increased risk donor organ. 16 days after transplant, she developed massive hematuria and was found to have renal allograft Rhizopus spp. involvement, we surmise to have been from donor-derived infection. Therapy included nephrectomy, debridement, liposomal amphotericin B, and posaconazole with survival. We reviewed PubMed indexed, English-language cases of isolated renal mucormycosis in general, in HIV/AIDS, and from donor-derived renal allograft infections.

Effect of Bamlanivimab as Monotherapy or in Combination With Etesevimab on Viral Load in Patients With Mild to Moderate COVID-19: A Randomized Clinical Trial.

Importance: Coronavirus disease 2019 (COVID-19) continues to spread rapidly worldwide. Neutralizing antibodies are a potential treatment for COVID-19. Objective: To determine the effect of bamlanivimab monotherapy and combination therapy with bamlanivimab and etesevimab on severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) viral load in mild to moderate COVID-19. Design, Setting, and Participants: The BLAZE-1 study is a randomized phase 2/3 trial at 49 US centers including ambulatory patients (N = 613) who tested positive for SARS-CoV-2 infection and had 1 or more mild to moderate symptoms. Patients who received bamlanivimab monotherapy or placebo were enrolled first (June 17-August 21, 2020) followed by patients who received bamlanivimab and etesevimab or placebo (August 22-September 3). These are the final analyses and represent findings through October 6, 2020. Interventions: Patients were randomized to receive a single infusion of bamlanivimab (700 mg [n = 101], 2800 mg [n = 107], or 7000 mg [n = 101]), the combination treatment (2800 mg of bamlanivimab and 2800 mg of etesevimab [n = 112]), or placebo (n = 156). Main Outcomes and Measures: The primary end point was change in SARS-CoV-2 log viral load at day 11 (±4 days). Nine prespecified secondary outcome measures were evaluated with comparisons between each treatment group and placebo, and included 3 other measures of viral load, 5 on symptoms, and 1 measure of clinical outcome (the proportion of patients with a COVID-19-related hospitalization, an emergency department [ED] visit, or death at day 29). Results: Among the 577 patients who were randomized and received an infusion (mean age, 44.7 [SD, 15.7] years; 315 [54.6%] women), 533 (92.4%) completed the efficacy evaluation period (day 29). The change in log viral load from baseline at day 11 was -3.72 for 700 mg, -4.08 for 2800 mg, -3.49 for 7000 mg, -4.37 for combination treatment, and -3.80 for placebo. Compared with placebo, the differences in the change in log viral load at day 11 were 0.09 (95% CI, -0.35 to 0.52; P = .69) for 700 mg, -0.27 (95% CI, -0.71 to 0.16; P = .21) for 2800 mg, 0.31 (95% CI, -0.13 to 0.76; P = .16) for 7000 mg, and -0.57 (95% CI, -1.00 to -0.14; P = .01) for combination treatment. Among the secondary outcome measures, differences between each treatment group vs the placebo group were statistically significant for 10 of 84 end points. The proportion of patients with COVID-19-related hospitalizations or ED visits was 5.8% (9 events) for placebo, 1.0% (1 event) for 700 mg, 1.9% (2 events) for 2800 mg, 2.0% (2 events) for 7000 mg, and 0.9% (1 event) for combination treatment. Immediate hypersensitivity reactions were reported in 9 patients (6 bamlanivimab, 2 combination treatment, and 1 placebo). No deaths occurred during the study treatment. Conclusions and Relevance: Among nonhospitalized patients with mild to moderate COVID-19 illness, treatment with bamlanivimab and etesevimab, compared with placebo, was associated with a statistically significant reduction in SARS-CoV-2 viral load at day 11; no significant difference in viral load reduction was observed for bamlanivimab monotherapy. Further ongoing clinical trials will focus on assessing the clinical benefit of antispike neutralizing antibodies in patients with COVID-19 as a primary end point. Trial Registration: ClinicalTrials.gov Identifier: NCT04427501.

COVID-19 in an HIV-positive kidney transplant recipient.

We report a case of a 50-year-old male with a history of HIV and kidney transplant who presented with SARS-CoV-2. We also present a review of COVID-19 cases in kidney transplant recipients.

Ventricular assist device-related infections and solid organ transplantation-Guidelines from the American Society of Transplantation Infectious Diseases Community of Practice.

The Infectious Diseases Community of Practice of the American Society of Transplantation has published evidenced-based guidelines on the prevention and management of infectious complications in SOT recipients since 2004. This updated guideline reviews the epidemiology of ventricular assist device (VAD) infections and provides recommendations for the management and prevention of these infections. Almost one half of those awaiting heart transplantation are supported with VADs. Despite advances in device technologies, VAD infections commonly complicate mechanical circulatory support and remain typified by common components and anatomic locations. These infections have important implications for transplant candidates, most notably increased wait-list mortality. Strategic management of these infections is crucial for successful transplantation. Coincidentally, explantation of all VAD components at the time of transplantation is often the definitive cure for the device-associated infection. Highlighted in this updated guideline is the reported success of transplantation in patients with a variety of pre-existing VAD infections and guidance on post-transplant management strategies.

Cytomegalovirus infection in heart transplantation: A single center experience.

BACKGROUND: Cytomegalovirus (CMV) infection remains a major complication after heart transplantation with varying prophylaxis strategies employed. We sought to determine the impact of valganciclovir (VGC) duration on the epidemiology of CMV infections after heart transplantation. METHODS: We performed a prospective cohort study of CMV donor (D) or recipient (R) seropositive heart transplant recipients from 2005 to 2012 who completed VGC prophylaxis, ranging from 3 to 12 months according to serostatus and induction immunosuppression. Univariate and multivariate logistic regression was performed. RESULTS: Among 159 heart transplant recipients during the study period, 130 (82%) were eligible for VGC prophylaxis. CMV D/R serostatus was as follows: 24% D+/R-, 30% D+/R+, and 29% D-/R+. 65% and 21% received basiliximab and thymoglobulin induction, respectively, followed by maintenance tacrolimus, mycophenolate mofetil, and prednisone. Twenty-one (16%) recipients suffered CMV infection. There was no association with comorbidities including diabetes mellitus, chronic kidney disease, or mechanical assist devices, nor were there associations with rejection, treatments of rejection, or mortality. When VGC prophylaxis duration was stratified by ≤6 vs ≥12 months, time from heart transplantation to CMV infection was delayed (median 247 vs 452 days, P = .002) but there was no difference in days from VGC discontinuation to onset of CMV infection (median 72 vs 83 days, P = .31). CMV infection occurred most frequently within 6-16 weeks of VGC cessation, and 95% of infections occurred during the 6 months post-prophylaxis period. CONCLUSIONS: Relative to ≤6 months, ≥12 months of VGC did not reduce incidence of CMV infection and only delayed time to onset. 95% of CMV infection occurs within 6 months after cessation of VGC.