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Background: Broadly neutralizing antibodies (bnAbs) are a promising approach for HIV-1 prevention. VRC07-523LS targets the CD4-binding site of Env and was engineered for increased breadth and half-life. In the only bnAb HIV prevention efficacy studies, the AMP studies, another CD4-binding site targeting bnAb, VRC01, was administered intravenously (IV). However, subcutaneous (SC) or intramuscular (IM) administration may be preferred. We present the first interim data comparing these routes of bnAb administration from the ongoing HVTN127/HPTN087 study. Methods: 124 healthy, HIV-uninfected participants were randomized to receive VRC07-523LS via the IV (2.5 mg/kg, 5 mg/kg, 20 mg/kg), SC (2.5 mg/kg, 5 mg/kg) or IM (2.5 mg/kg, placebo) routes. Safety data were collected for 112 weeks following the first administration. VRC07-523LS serum concentrations were measured by ELISA at Day 0, 3, 6, 28, 56, 84, and 112. The log-linear portion of the time-concentration curve was used to estimate the elimination half-life. Results: Injections were well-tolerated, with mild pain or tenderness reported commonly in the SC and IM groups and mild to moderate erythema or induration reported commonly in the SC groups. Infusions were generally well-tolerated, with infusion reactions reported in 3 participants in the 20 mg/kg IV group. VRC07-523LS has an estimated median half-life of ~40 days. Median peak concentrations (with interquartile range) were 42.2 (35.1, 52.7) [mu]g/mL, 80.3 (72.3, 106.1) [mu]g/mL, and 353.6 (278.0, 461.97) [micro]g/mL for the IV groups; 11.4 (8.4, 15.2) [micro]g/mL and 24.5 (18.8, 27.0) [micro]g/mL for the SC groups; and 17.8 (15.5, 19.1) [micro]g/mL for the IM group. Geometric mean trough concentrations were 3.4 (2.5, 4.6) [micro]g/mL, 6.5 (5.6, 7.5) [micro]g/mL, and 27.2 (23.9, 31.0) [micro]g/mL for the IV groups; 0.9 (0.6, 1.4) [micro]g/mL and 3.1 (2.2, 4.3) [micro]g/mL for the SC groups; and 2.6 (2.1, 3.3) [micro]g/mL for the IM group. The peak VRC07-523LS serum concentrations increased linearly with the administered dose. At a given dose, peak and trough concentrations were highest in the IV groups and lowest in the SC groups. Conclusions: VRC07-523LS appears to be safe and well-tolerated across a range of doses and routes and is a promising bnAb for inclusion in HIV-1 prevention regimens., OA03.01 S. Walsh (1); C. Gay (2); S. Karuna (3); O. Hyrien (3); T. Skalland (3); K.H. Mayer (4); M. Sobieszczyk (5); P. Andrew (6); C. Karg (3); J. Baumblatt [...]

BACKGROUND The safety and efficacy of the AZD1222 (ChAdOxl nCoV-19) vaccine in a large, diverse population at increased risk for severe acute respiratory syndrome corona-virus 2 (SARS-CoV-2) infection in the United States, Chile, and Peru has not been known. METHODS In this ongoing, double-blind, randomized, placebo-controlled, phase 3 clinical trial, we investigated the safety, vaccine efficacy, and immunogenicity of two doses of AZD1222 as compared with placebo in preventing the onset of symptom-atic and severe coronavirus disease 2019 (Covid-19) 15 days or more after the second dose in adults, including older adults, in the United States, Chile, and Peru. RESULTS A total of 32,451 participants underwent randomization, in a 2:1 ratio, to receive AZD1222 (21,635 participants) or placebo (10,816 participants). AZD1222 was safe, with low incidences of serious and medically attended adverse events and adverse events of special interest; the incidences were similar to those observed in the placebo group. Solicited local and systemic reactions were generally mild or moderate in both groups. Overall estimated vaccine efficacy was 74.0% (95% confidence interval [CI], 65.3 to 80.5; P<0.001) and estimated vaccine efficacy was 83.5% (95% CI, 54.2 to 94.1) in participants 65 years of age or older. High vaccine efficacy was consistent across a range of demographic subgroups. In the fully vaccinated analysis subgroup, no severe or critical symptomatic Covid-19 cases were observed among the 17,662 participants in the AZD1222 group; 8 cases were noted among the 8550 participants in the placebo group (<0.1%). The estimated vaccine efficacy for preventing SARS-CoV-2 infection (nucleocapsid antibody sero¬conversion) was 64.3% (95% CI, 56.1 to 71.0; P<0.001). SARS-CoV-2 spike protein binding and neutralizing antibodies increased after the first dose and increased further when measured 28 days after the second dose. CONCLUSIONS AZD1222 was safe and efficacious in preventing symptomatic and severe Covid-19 across diverse populations that included older adults. (Funded by AstraZeneca and others; ClinicalTrials.gov number, NCT04516746.) [ABSTRACT FROM AUTHOR]

Background. The co-occurrence of HIV infection and severe malnutrition contributes to high rates of morbidity and mortality among children in resource-limited settings. Lactose-free, ready-to-use therapeutic feeds (RUTFs) may be most appropriate in this population because of underlying mucosal damage secondary to inflammation and infection. Objectives. To describe the effect of lactose-free RUTFs on the growth parameters of severely malnourished HIV-infected children in Durban, South Africa (SA). Methods. This was a prospective, observational study of nutritional recovery in HIV-infected, severely malnourished children, aged 6 months to 5 years, who received lactose-free RUTFs following admission to King Edward VIII Hospital in Durban, SA. The primary outcome was nutritional recovery, defined as 15% weight gain from enrolment to end of study. Secondary outcomes included z-scores for weight-for-height, weight-for-age, height-for-age, triceps skinfold thickness (SFT) and subscapular SFT calculated at baseline and 7, 14, 30 and 45 days after admission. Univariate analysis was done to compare outcomes among antiretroviral therapy (ART)-naive and ART-experienced children; the effect of ART on nutritional recovery was evaluated in a logistic regression model. Results. A significant improvement in most nutritional parameters was found at 45 days; 59% of children attained nutritional recovery. There was no significant difference in the proportion of children reaching recovery based on ART status at admission (p=0.08). Conclusion. Lactose-free formula feeds may be an effective strategy for nutritional rehabilitation of severely malnourished and HIV-infected children in resource-limited settings. It remains to be determined how ART initiation affects nutritional recovery in these children. [ABSTRACT FROM AUTHOR]

Abstract Background The relationship between HIV serostatus disclosure and sexual risk behavior is inconsistent across studies. As men who have sex with men (MSM) are emerging as the key affected population in Bangkok, Thailand with reported HIV prevalence of 30%, we assessed whether HIV disclosure is associated with protected sex in this population. Methods A risk behavior questionnaire was administered using Audio Computer-Assisted Self-Interviewing (ACASI) to determine whether HIV serostatus disclosure was associated with protected sex in 200 HIV-positive MSM in Bangkok. HIV serostatus disclosure to the most recent sexual partner prior to or at the time of the sexual encounter was assessed. Protected sex was defined as insertive or receptive anal intercourse with a condom at the most recent sexual encounter. Results The mean age was 30.2 years, CD4 was 353 cells/mm3, and one-third was on antiretroviral therapy. At the most recent sexual encounter, HIV serostatus disclosure rate was low (26%); 60.5% of subjects had not discussed their serostatus at all, while 5.5% had not revealed their true serostatus. Seventeen percent reported unprotected anal intercourse and about half had sex with their primary partners. The serostatus of the most recent sexual partner was HIV-positive in 19.2%, HIV-negative in 26.4%, and unknown in 54.4% of subjects. There was no association between disclosure and protected sex, with 41 of 48 (85.4%) disclosers and 104 of 126 (82.5%) of non-disclosers reported protected sex (p = .65). Subjects with HIV-positive partners were less likely to report protected sex overall (20 of 33, 60.6%) compared to those with HIV negative (82 of 96, 85.4%) or unknown (41 of 45, 91.1%) partners (p = .001). Age (27-32 years vs. ≤26 years, p = .008), primary partner status (p < .001), and HIV-positive serostatus of sexual partner (p Conclusion Rates of HIV disclosure to sexual partners by HIV-positive MSM in Bangkok are low. Despite low rates of HIV serostatus disclosure, most HIV-positive MSM reported protected sex with their partners at risk for infection. Future studies should focus on understanding barriers to disclosure and factors driving risk behavior amongst MSM in Thailand.

Abstract Background Dengue fever is a mosquito-borne illness that places significant burden on tropical developing countries with unplanned urbanization. A surveillance system using Google Earth and GIS mapping technologies was developed in Nicaragua as a management tool. Methods and Results Satellite imagery of the town of Bluefields, Nicaragua captured from Google Earth was used to create a base-map in ArcGIS 9. Indices of larval infestation, locations of tire dumps, cemeteries, large areas of standing water, etc. that may act as larval development sites, and locations of the homes of dengue cases collected during routine epidemiologic surveying were overlaid onto this map. Visual imagery of the location of dengue cases, larval infestation, and locations of potential larval development sites were used by dengue control specialists to prioritize specific neighborhoods for targeted control interventions. Conclusion This dengue surveillance program allows public health workers in resource-limited settings to accurately identify areas with high indices of mosquito infestation and interpret the spatial relationship of these areas with potential larval development sites such as garbage piles and large pools of standing water. As a result, it is possible to prioritize control strategies and to target interventions to highest risk areas in order to eliminate the likely origin of the mosquito vector. This program is well-suited for resource-limited settings since it utilizes readily available technologies that do not rely on Internet access for daily use and can easily be implemented in many developing countries for very little cost.

Abstract: This study, completed at an sexually transmitted infection (STI) clinic in 2019 to 2020, evaluated patient preferences for telemedicine, express, and standard visits. Active PrEP users preferred telemedicine and express visits, patients with prior STIs preferred express visits, and cisgender women preferred standard visits. Configuring STI clinic visit types requires shared decision making and individualization., Competing Interests: Conflict of Interest and Sources of Funding: All authors have no conflict of interest to disclose in relation to this study. J.Z. is supported by the National Institute of Allergy and Infectious Diseases of the National Institute of Health under award number K23AI150278., (Copyright © 2023 American Sexually Transmitted Diseases Association. All rights reserved.)

In the phase 3 trial of the AZD1222 (ChAdOx1 nCoV-19) vaccine conducted in the U.S., Chile, and Peru, anti-spike binding IgG concentration (spike IgG) and pseudovirus 50% neutralizing antibody titer (nAb ID50) measured four weeks after two doses were assessed as correlates of risk and protection against PCR-confirmed symptomatic SARS-CoV-2 infection (COVID-19). These analyses of SARS-CoV-2 negative participants were based on case-cohort sampling of vaccine recipients (33 COVID-19 cases by 4 months post dose two, 463 non-cases). The adjusted hazard ratio of COVID-19 was 0.32 (95% CI: 0.14, 0.76) per 10-fold increase in spike IgG concentration and 0.28 (0.10, 0.77) per 10-fold increase in nAb ID50 titer. At nAb ID50 below the limit of detection (< 2.612 IU50/ml), 10, 100, and 270 IU50/ml, vaccine efficacy was -5.8% (-651%, 75.6%), 64.9% (56.4%, 86.9%), 90.0% (55.8%, 97.6%) and 94.2% (69.4%, 99.1%). These findings provide further evidence towards defining an immune marker correlate of protection to help guide regulatory/approval decisions for COVID-19 vaccines., (© 2023. The Author(s).)

Importance: The COVID-19 pandemic has caused millions of infections and deaths and resulted in unprecedented international public health social and economic crises. As SARS-CoV-2 spread across the globe and its impact became evident, the development of safe and effective vaccines became a priority. Outlining the processes used to establish and support the conduct of the phase 3 randomized clinical trials that led to the rapid emergency use authorization and approval of several COVID-19 vaccines is of major significance for current and future pandemic response efforts., Observations: To support the rapid development of vaccines for the US population and the rest of the world, the National Institute of Allergy and Infectious Diseases established the COVID-19 Prevention Network (CoVPN) to assist in the coordination and implementation of phase 3 efficacy trials for COVID-19 vaccine candidates and monoclonal antibodies. By bringing together multiple networks, CoVPN was able to draw on existing clinical and laboratory infrastructure, community partnerships, and research expertise to quickly pivot clinical trial sites to conduct COVID-19 vaccine trials as soon as the investigational products were ready for phase 3 testing. The mission of CoVPN was to operationalize phase 3 vaccine trials using harmonized protocols, laboratory assays, and a single data and safety monitoring board to oversee the various studies. These trials, while staggered in time of initiation, overlapped in time and course of conduct and ultimately led to the successful completion of multiple studies and US Food and Drug Administration-licensed or -authorized vaccines, the first of which was available to the public less than 1 year from the discovery of the virus., Conclusions and Relevance: This Special Communication describes the design, geographic distribution, and underlying principles of conduct of these efficacy trials and summarizes data from 136 382 prospectively followed-up participants, including more than 2500 with documented COVID-19. These successful efforts can be replicated for other important research initiatives and point to the importance of investments in clinical trial infrastructure integral to pandemic preparedness.

HIV pre-exposure prophylaxis (PrEP) effectively reduces new HIV diagnoses. High rates of incident bacterial sexually transmitted infections (STIs) have been observed in patients eligible for and adherent to PrEP. Observational studies generally report low long-term retention in PrEP care. Limited data exist on the rates of bacterial STI diagnosis upon re-engagement with PrEP services. We conducted a retrospective chart review within the HIV prevention program of an urban academic medical center in New York City. Eligible patients started PrEP from 2015 to 2019, then resumed PrEP services after a gap in care of at least 180 days. Demographic, clinical, and laboratory data were used to characterize the patient population and rates of bacterial STI diagnosis at re-engagement. In total, 286 patients were identified, with 316 qualifying re-engagement visits. Twenty-nine percent of patients had continued PrEP during the care gap, and 30% reported discontinuing medication due to a perceived change in risk. A new STI was diagnosed at 19% of re-engagement visits. There was no statistically significant difference in rates of new STI between individuals returning on or off PrEP, nor between those with perceived lower risk and those without. Individuals who fall out of PrEP services and subsequently re-engage remain at high risk of bacterial STI during the gap in care, regardless of whether PrEP medication is continued or the patient perceives themselves to be at lower HIV acquisition risk. Providers should strongly encourage patients discontinuing PrEP to remain engaged in sexual health services. Alternatives to clinic-based PrEP care must still include regular bacterial STI screening.

Background: Many regions have experienced successive epidemic waves of coronavirus disease 2019 (COVID-19) since the emergence of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), with heterogeneous differences in mortality. Elucidating factors differentially associated with mortality between epidemic waves may inform clinical and public health strategies., Methods: We examined clinical and demographic data among patients admitted with COVID-19 during the first (March-August 2020) and second (August 2020-March 2021) epidemic waves at an academic medical center in New York City., Results: Hospitalized patients (n = 4631) had lower overall and 30-day in-hospital mortality, defined as death or discharge to hospice, during the second wave (14% and 11%) than the first (22% and 21%). The wave 2 in-hospital mortality decrease persisted after adjusting for several potential confounders. Adjusting for the volume of COVID-19 admissions, a measure of health system strain, accounted for the mortality difference between waves. Several demographic and clinical patient factors were associated with an increased risk of mortality independent of wave: SARS-CoV-2 cycle threshold, do-not-intubate status, oxygen requirement, and intensive care unit admission., Conclusions: This work suggests that the increased in-hospital mortality rates observed during the first epidemic wave were partly due to strain on hospital resources. Preparations for future epidemics should prioritize evidence-based patient risks, treatment paradigms, and approaches to augment hospital capacity., (© The Author(s) 2022. Published by Oxford University Press on behalf of Infectious Diseases Society of America.)

Background: Eliciting durable humoral immunity with sufficient breadth and magnitude is important for HIV-1 vaccine design. The HVTN 114 vaccine trial evaluated different boost regimens administered after a 7-year rest period in participants previously enrolled in HVTN 205, who received either three MVA/HIV62B (MMM) or two DNA and two MVA/HIV62B (DDMM) injections; both vaccines expressed multiple HIV-1 antigens in non-infectious virus-like-particles. The primary objective of HVTN 114 was to assess the impact of a heterologous gp120 protein AIDSVAX B/E boost on the magnitude, breadth and durability of vaccine-induced immune responses., Methods: We enrolled 27 participants from HVTN 205 into five groups. Eight participants who previously received MMM were randomized and boosted with either MVA/HIV62B alone (T1; n = 4) or MVA/HIV62B and AIDSVAX B/E (T2; n = 4). Nineteen participants who received DDMM were randomized and boosted with MVA/HIV62B alone (T3; n = 6), MVA/HIV62B and AIDSVAX B/E (T4; n = 6), or AIDSVAX B/E alone (T5; n = 7). Boosts were at months 0 and 4. Participants were followed for safety and immunogenicity for 10 months and were pooled for analysis based on the regimen: MVA-only (T1 + T3), MVA + AIDSVAX (T2 + T4), and AIDSVAX-only (T5)., Results: All regimens were safe and well-tolerated. Prior to the boost vaccination, binding antibody and CD4+T-cell responses were observed 7 years after HVTN 205 vaccinations. Late boosting with AIDSVAX, with or without MVA, resulted in high binding antibody responses to gp120 and V1V2 epitopes, with increased magnitude and breadth compared to those observed in HVTN 205. Late boosting with MVA, with or without AIDSVAX, resulted in increased gp140 and gp41 antibody responses and higher CD4+T-cell responses to Env and Gag., Conclusions: Late boosting with AIDSVAX, alone or in combination with MVA, can broaden binding antibody responses and increase T-cell responses even years following the original MVA/HIV62B with or without DNA-priming vaccine., Competing Interests: Declaration of Competing Interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: [The authors of this manuscript have read the journal's policy and have the following competing interests: YH, CY, MDM, CP, SCD, KC, MJM, PG, JM, MK, MS, LRB, DM are recipients of funding from The National Institute of Allergy and Infectious Diseases (NIAID) of the National Institutes of Health, and this publication is a result of activities funded by the NIAID. HLR was a co-founder of GeoVax, Inc. and is an inventor on patents that GeoVax licensed from Emory University and the NIAID for commercial development of the MVA/HIV62B and JS7 DNA vaccines. CFK receives research grants to her institution from NIH, CDC, Gilead Sciences, ViiV, Moderna, and Novavax. GDT received research grants to her institution from NIAID, BMGF, GSK and Macrogenics, has patent applications for HIV vaccine design and incidence testing, and has consulted for Axon Advisors. KES has a patent application for HIV incidence testing. SB receives research grants to her institution from NIH, Gilead Sciences, Merck, and Viiv. The rest of the authors have no conflicts., (Published by Elsevier Ltd.)

The COVID-19 pandemic has had widespread effects across the globe, and its causative agent, SARS-CoV-2, continues to spread. Effective interventions need to be developed to end this pandemic. Single and combination therapies with monoclonal antibodies have received emergency use authorization 1-3 , and more treatments are under development 4-7 . Furthermore, multiple vaccine constructs have shown promise 8 , including two that have an approximately 95% protective efficacy against COVID-19 9,10 . However, these interventions were directed against the initial SARS-CoV-2 virus that emerged in 2019. The recent detection of SARS-CoV-2 variants B.1.1.7 in the UK 11 and B.1.351 in South Africa 12 is of concern because of their purported ease of transmission and extensive mutations in the spike protein. Here we show that B.1.1.7 is refractory to neutralization by most monoclonal antibodies against the N-terminal domain of the spike protein and is relatively resistant to a few monoclonal antibodies against the receptor-binding domain. It is not more resistant to plasma from individuals who have recovered from COVID-19 or sera from individuals who have been vaccinated against SARS-CoV-2. The B.1.351 variant is not only refractory to neutralization by most monoclonal antibodies against the N-terminal domain but also by multiple individual monoclonal antibodies against the receptor-binding motif of the receptor-binding domain, which is mostly due to a mutation causing an E484K substitution. Moreover, compared to wild-type SARS-CoV-2, B.1.351 is markedly more resistant to neutralization by convalescent plasma (9.4-fold) and sera from individuals who have been vaccinated (10.3-12.4-fold). B.1.351 and emergent variants 13,14 with similar mutations in the spike protein present new challenges for monoclonal antibody therapies and threaten the protective efficacy of current vaccines.

Background: The Antibody-Mediated Prevention trials (HVTN 704/HPTN 085 and HVTN 703/HPTN 081) are the first efficacy trials to evaluate whether VRC01, a broadly neutralizing monoclonal antibody targeting the CD4-binding site of the HIV envelope protein, prevents sexual transmission of HIV-1. HVTN 704/HPTN 085 enrolled 2701 cisgender men and transgender (TG) individuals who have sex with men at 26 sites in Brazil, Peru, Switzerland, and the United States., Methods: Participants were recruited and retained through early, extensive community engagement. Eligible participants were randomized 1:1:1 to 10 mg/kg or 30 mg/kg of VRC01 or saline placebo. Visits occurred monthly, with intravenous (IV) infusions every 8 weeks over 2 years, for a total of 10 infusions. Participants were followed for 104 weeks after first infusion., Results: The median HVTN 704/HPTN 085 participant age was 28 years; 99% were assigned male sex; 90% identified as cisgender men, 5% as TG women and the remaining as other genders. Thirty-two percent were White, 15% Black, and 57% Hispanic/Latinx. Twenty-eight percent had a sexually transmitted infection at enrollment. More than 23,000 infusions were administered with no serious IV administration complications. Overall, retention and adherence to the study schedule exceeded 90%, and the dropout rate was below 10% annually (7.3 per 100 person-years) through week 80, the last visit for the primary end point., Conclusions: HVTN 704/HPTN 085 exceeded accrual and retention expectations. With exceptional safety of IV administration and operational feasibility, it paves the way for future large-scale monoclonal antibody trials for HIV prevention and/or treatment., Competing Interests: P.L.A. has received personal fees and research funds paid to his institution from Gilead Sciences. J.R.M. is an inventor on NIH patent for VRC01. The remaining authors have no conflicts of interest to disclose., (Copyright © 2021 Wolters Kluwer Health, Inc. All rights reserved.)

New York City is the metropolitan area in the United States with the highest number of new HIV diagnoses nationwide. The End-The-Epidemic (EtE) initiative calls for identifying persons with HIV who remain undiagnosed, linking and retaining persons living with HIV to maximize viral suppression, and facilitate access to pre-exposure prophylaxis (PrEP) for patients at increased risk of HIV. HIV screening represents the first step to both the primary and secondary HIV prevention cascades. We conducted an online, anonymous, cross-sectional survey of residents at all stages of training within four residency programs at one institution in Northern Manhattan between August 2017 and August 2018. All internal medicine, emergency medicine, obstetrics and gynecology trainees, and pediatrics were invited to complete the survey via email. Of 298 eligible trainees, 142 (48%) completed the survey. Most trainees were aware of the HIV testing law and agreed that HIV testing was their responsibility, but few successfully screened most of their patients. Most trainees were not knowledgeable about non-occupational post-exposure prophylaxis (nPEP) or PrEP, but felt that it was important to provide these services across settings. Barriers to HIV, nPEP, and PrEP varied across specialties. Ending the HIV epidemic will require efforts across clinical specialties. In this survey from an EtE jurisdiction, most trainees felt that it is important to provide HIV prevention services in most settings; however, their knowledge and comfort with HIV prevention services other than testing were low. Barriers varied across specialties, and developing specialty-specific materials for trainees may be beneficial.

Background: The surge of coronavirus 2019 (COVID-19) hospitalizations in New York City required rapid discharges to maintain hospital capacity., Objective: To determine whether lenient provisional discharge guidelines with remote monitoring after discharge resulted in safe discharges home for patients hospitalized with COVID-19 illness., Design: Retrospective case series SETTING: Tertiary care medical center PATIENTS: Consecutive adult patients hospitalized with COVID-19 illness between March 26, 2020, and April 8, 2020, with a subset discharged home INTERVENTIONS: COVID-19 Discharge Care Program consisting of lenient provisional inpatient discharge criteria and option for daily telephone monitoring for up to 14 days after discharge MEASUREMENTS: Fourteen-day emergency department (ED) visits and hospital readmissions RESULTS: Among 812 patients with COVID-19 illness hospitalized during the study time period, 15.5% died prior to discharge, 24.1% remained hospitalized, 10.0% were discharged to another facility, and 50.4% were discharged home. Characteristics of the 409 patients discharged home were mean (SD) age 57.3 (16.6) years; 245 (59.9%) male; 27 (6.6%) with temperature ≥ 100.4 °F; and 154 (37.7%) with oxygen saturation < 95% on day of discharge. Over 14 days of follow-up, 45 patients (11.0%) returned to the ED, of whom 31 patients (7.6%) were readmitted. Compared to patients not referred, patients referred for remote monitoring had fewer ED visits (8.3% vs 14.1%; OR 0.60, 95% CI 0.31-1.15, p = 0.12) and readmissions (6.9% vs 8.3%; OR 1.15, 95% CI 0.52-2.52, p = 0.73)., Limitations: Single-center study; assignment to remote monitoring was not randomized., Conclusions: During the COVID-19 surge in New York City, lenient discharge criteria in conjunction with remote monitoring after discharge were associated with a rate of early readmissions after COVID-related hospitalizations that was comparable to the rate of readmissions after other reasons for hospitalization before the COVID pandemic.

Background: The clinical impact of coronavirus disease 2019 (COVID-19) among people with HIV (PWH) remains unclear. In this retrospective cohort study of COVID-19, we compared clinical outcomes and laboratory parameters among PWH and controls., Methods: Sixty-eight PWH diagnosed with COVID-19 were matched 1:4 to patients without known HIV diagnosis, drawn from a study population of all patients who were diagnosed with COVID-19 at an academic urban hospital. The primary outcome was death/discharge to hospice within 30 days of hospital presentation., Results: PWH were more likely to be admitted from the emergency department than patients without HIV (91% vs 71%; P  = .001). We observed no statistically significant difference between admitted PWH and patients without HIV in terms of 30-day mortality rate (19% vs 13%, respectively) or mechanical ventilation rate (18% vs 20%, respectively). PWH had higher erythrocyte sedimentation rates than controls on admission but did not differ in other inflammatory marker levels or nasopharyngeal/oropharyngeal severe acute respiratory syndrome coronavirus 2 viral load estimated by reverse transcriptase polymerase chain reaction cycle thresholds., Conclusions: HIV infection status was associated with a higher admission rate; however, among hospitalized patients, PWH did not differ from HIV-uninfected controls by rate of mechanical ventilation or death/discharge to hospice., (© The Author(s) 2021. Published by Oxford University Press on behalf of Infectious Diseases Society of America.)

Immediate antiretroviral therapy (iART), defined as same-day initiation of ART or as soon as possible after diagnosis, has recently been recommended by global and national clinical care guidelines for patients newly diagnosed with human immunodeficiency virus (HIV). Based on San Francisco's Rapid ART Program Initiative for HIV Diagnoses (RAPID) model, most iART programs in the US condense ART initiation, insurance acquisition, housing assessment, and mental health and substance use evaluation into an initial visit. However, the RAPID model does not explicitly address structural racism and homophobia, HIV-related stigma, medical mistrust, and other important factors at the time of diagnosis experienced more poignantly by African American, Latinx, men who have sex with men (MSM), and transgender patient populations. These factors negatively impact initial and subsequent HIV care engagement and exacerbate significant health disparities along the HIV care continuum. While iART has improved time to viral suppression and linkage to care rates, its association with retention in care and viral suppression, particularly in vulnerable populations, remains controversial. Considering that in the US the HIV epidemic is sharply defined by healthcare disparities, we argue that incorporating an explicit health equity approach into the RAPID model is vital to ensure those who disproportionately bear the burden of HIV are not left behind.

A surge of patients with coronavirus disease 2019 (COVID-19) presenting to New York City hospitals in March 2020 led to a sharp increase in blood culture utilization, which overwhelmed the capacity of automated blood culture instruments. We sought to evaluate the utilization and diagnostic yield of blood cultures during the COVID-19 pandemic to determine prevalence and common etiologies of bacteremia and to inform a diagnostic approach to relieve blood culture overutilization. We performed a retrospective cohort analysis of 88,201 blood cultures from 28,011 patients at a multicenter network of hospitals within New York City to evaluate order volume, positivity rate, time to positivity, and etiologies of positive cultures in COVID-19. Ordering volume increased by 34.8% in the second half of March 2020 compared to the level in the first half of the month. The rate of bacteremia was significantly lower among COVID-19 patients (3.8%) than among COVID-19-negative patients (8.0%) and those not tested (7.1%) ( P  < 0.001). COVID-19 patients had a high proportion of organisms reflective of commensal skin microbiota, which, when excluded, reduced the bacteremia rate to 1.6%. More than 98% of all positive cultures were detected within 4 days of incubation. Bloodstream infections are very rare for COVID-19 patients, which supports the judicious use of blood cultures in the absence of compelling evidence for bacterial coinfection. Clear communication with ordering providers is necessary to prevent overutilization of blood cultures during patient surges, and laboratories should consider shortening the incubation period from 5 days to 4 days, if necessary, to free additional capacity., (Copyright © 2020 American Society for Microbiology.)

T cell responses have been implicated in reduced risk of HIV acquisition in uninfected persons and control of viral replication in HIV-infected individuals. HIV Gag-specific T cells have been predominantly associated with post-infection control, whereas Env antigens are the target for protective antibodies; therefore, inclusion of both antigens is common in HIV vaccine design. However, inclusion of multiple antigens may provoke antigenic competition, reducing the potential effectiveness of the vaccine. HVTN 084 was a randomized, multicenter, double-blind phase 1 trial to investigate whether adding Env to a Gag/Pol vaccine decreases the magnitude or breadth of Gag/Pol-specific T cell responses. Fifty volunteers each received one intramuscular injection of 1 × 10 10 particle units (PU) of rAd5 Gag/Pol and EnvA/B/C (3:1:1:1 mixture) or 5 × 10 9 PU of rAd5 Gag/Pol. CD4 + T cell responses to Gag/Pol measured 4 weeks after vaccination by cytokine expression were significantly higher in the group vaccinated without Env, whereas CD8 + T cell responses did not differ significantly between the two groups. Mapping of individual epitopes revealed greater breadth of the Gag/Pol-specific T cell response in the absence of Env compared to Env coimmunization. Addition of an Env component to a Gag/Pol vaccine led to reduced Gag/Pol CD4 + T cell response rate and magnitude as well as reduced epitope breadth, confirming the presence of antigenic competition. Therefore, T cell-based vaccine strategies should aim at choosing a minimalist set of antigens to reduce interference of individual vaccine components with the induction of the maximally achievable immune response., (Copyright © 2019 The Authors, some rights reserved; exclusive licensee American Association for the Advancement of Science. No claim to original U.S. Government Works.)

Background: HVTN 505 was a human immunodeficiency virus type 1 (HIV-1) preventive vaccine efficacy trial of a DNA/recombinant adenovirus serotype 5 (rAd5) vaccine regimen. We assessed antibody responses measured 1 month after final vaccination (month 7) as correlates of HIV-1 acquisition risk., Methods: Binding antibody responses were quantified in serum samples from 25 primary endpoint vaccine cases (diagnosed with HIV-1 infection between month 7 and month 24) and 125 randomly sampled frequency-matched vaccine controls (HIV-1 negative at month 24). We prespecified for a primary analysis tier 6 antibody response biomarkers that measure immunoglobulin G (IgG) and immunoglobulin A (IgA) binding to Env proteins and 2 previously assessed T-cell response biomarkers., Results: Envelope-specific IgG responses were significantly correlated with decreased HIV-1 risk. Moreover, the interaction of IgG responses and Env-specific CD8+ T-cell polyfunctionality score had a highly significant association with HIV-1 risk after adjustment for multiple comparisons., Conclusions: Vaccinees with higher levels of Env IgG have significantly decreased HIV-1 risk when CD8+ T-cell responses are low. Moreover, vaccinees with high CD8+ T-cell responses generally have low risk, and those with low CD8+ T-cell and low Env antibody responses have high risk. These findings suggest the critical importance of inducing a robust IgG Env response when the CD8+ T-cell response is low.

Background: It is important to identify vaccine-induced immune responses that predict the preventative efficacy of a human immunodeficiency virus (HIV)-1 vaccine. We assessed T-cell response markers as correlates of risk in the HIV Vaccine Trials Network (HVTN) 505 HIV-1 vaccine efficacy trial., Methods: 2504 participants were randomized to DNA/rAd5 vaccine or placebo, administered at weeks 0, 4, 8, and 24. Peripheral blood mononuclear cells were obtained at week 26 from all 25 primary endpoint vaccine cases and 125 matched vaccine controls, and stimulated with vaccine-insert-matched peptides. Primary variables were total HIV-1-specific CD4+ T-cell magnitude and Env-specific CD4+ polyfunctionality. Four secondary variables were also assessed. Immune responses were evaluated as predictors of HIV-1 infection among vaccinees using Cox proportional hazards models. Machine learning analyses identified immune response combinations best predicting HIV-1 infection., Results: We observed an unexpectedly strong inverse correlation between Env-specific CD8+ immune response magnitude and HIV-1 infection risk (hazard ratio [HR] = 0.18 per SD increment; P = .04) and between Env-specific CD8+ polyfunctionality and infection risk (HR = 0.34 per SD increment; P < .01)., Conclusions: Further research is needed to determine if these immune responses are predictors of vaccine efficacy or markers of natural resistance to HIV-1 infection., (© The Author 2017. Published by Oxford University Press for the Infectious Diseases Society of America. All rights reserved. For permissions, e-mail journals.permissions@oup.com.)

Background: Service members deploying to Afghanistan (OEF) and Iraq (OIF) often return with respiratory symptoms. We sought to determine prevalence of lung function abnormalities following OEF/OIF., Methods: We identified OEF/OIF patients who had unexplained respiratory symptoms evaluated using lung function testing. Lung function data were summarized and analyzed for associations with demographic and deployment characteristics., Results: We found 267 patients with unexplained cough or dyspnea, lung function testing and a history of OEF/OIF deployment. All patients had basic spirometry performed and 82 had diffusion capacity for carbon dioxide (DLCO) measured. The median (IQR) number of deployments and total days deployed were 1 (1-2) and 352.0 (209-583), respectively. There were 83 (36.6%) patients with abnormal spirometry, 53 (63.9%) of whom had an abnormal FEV1/FVC. Only one (1.2%) patient had an abnormal DLCO adjusted for alveolar volume. Of 104 patients who had post bronchodilator (BD) testing performed, six (5.8%) had a positive response by ATS criteria. We found no relationships between lung function and time in theater, deployment location, deployment frequency, or land based-deployment. Dyspnea and enlisted rank were associated with tobacco use and lower FEV1, and cough was associated with total number of deployments., Conclusions: Service members with respiratory complaints following OEF/OIF have a high prevalence of abnormalities on spirometry. Tobacco use, enlisted rank and total number of deployments were associated with symptoms or spirometric abnormalities., (Published by Elsevier Ltd.)

Background: Prompt diagnosis of acute HIV infection (AHI) benefits the individual and provides opportunities for public health intervention. The aim of this study was to describe most common signs and symptoms of AHI, correlate these with early disease progression and develop a clinical algorithm to identify acute HIV cases in resource limited setting., Methods: 245 South African women at high-risk of HIV-1 were assessed for AHI and received monthly HIV-1 antibody and RNA testing. Signs and symptoms at first HIV-positive visit were compared to HIV-negative visits. Logistic regression identified clinical predictors of AHI. A model-based score was assigned to each predictor to create a risk score for every woman., Results: Twenty-eight women seroconverted after a total of 390 person-years of follow-up with an HIV incidence of 7.2/100 person-years (95%CI 4.5-9.8). Fifty-seven percent reported ≥1 sign or symptom at the AHI visit. Factors predictive of AHI included age <25 years (OR = 3.2; 1.4-7.1), rash (OR = 6.1; 2.4-15.4), sore throat (OR = 2.7; 1.0-7.6), weight loss (OR = 4.4; 1.5-13.4), genital ulcers (OR = 8.0; 1.6-39.5) and vaginal discharge (OR = 5.4; 1.6-18.4). A risk score of 2 correctly predicted AHI in 50.0% of cases. The number of signs and symptoms correlated with higher HIV-1 RNA at diagnosis (r = 0.63; p<0.001)., Conclusions: Accurate recognition of signs and symptoms of AHI is critical for early diagnosis of HIV infection. Our algorithm may assist in risk-stratifying individuals for AHI, especially in resource-limited settings where there is no routine testing for AHI. Independent validation of the algorithm on another cohort is needed to assess its utility further. Point-of-care antigen or viral load technology is required, however, to detect asymptomatic, antibody negative cases enabling early interventions and prevention of transmission.

Background: DNA vaccines are a promising approach to vaccination since they circumvent the problem of vector-induced immunity. DNA plasmid cytokine adjuvants have been shown to augment immune responses in small animals and in macaques., Methodology/principal Findings: We performed two first in human HIV vaccine trials in the US, Brazil and Thailand of an RNA-optimized truncated HIV-1 gag gene (p37) DNA derived from strain HXB2 administered either alone or in combination with dose-escalation of IL-12 or IL-15 plasmid cytokine adjuvants. Vaccinations with both the HIV immunogen and cytokine adjuvant were generally well-tolerated and no significant vaccine-related adverse events were identified. A small number of subjects developed asymptomatic low titer antibodies to IL-12 or IL-15. Cellular immunogenicity following 3 and 4 vaccinations was poor, with response rates to gag of 4.9%/8.7% among vaccinees receiving gag DNA alone, 0%/11.5% among those receiving gag DNA+IL-15, and no responders among those receiving DNA+high dose (1500 ug) IL-12 DNA. However, after three doses, 44.4% (4/9) of vaccinees receiving gag DNA and intermediate dose (500 ug) of IL-12 DNA demonstrated a detectable cellular immune response., Conclusions/significance: This combination of HIV gag DNA with plasmid cytokine adjuvants was well tolerated. There were minimal responses to HIV gag DNA alone, and no apparent augmentation with either IL-12 or IL-15 plasmid cytokine adjuvants. Despite the promise of DNA vaccines, newer formulations or methods of delivery will be required to increase their immunogenicity., Trial Registration: Clinicaltrials.gov NCT00115960 NCT00111605.

Background: HIV-positive patients at HELP/PSI, Inc, an in-patient drug rehabilitation center, had a high baseline prevalence of Staphylococcus aureus colonization (49%) and incidence of infection (17%) in a previous year-long study., Methods: A randomized, double-blinded, placebo-controlled study was conducted to determine whether repeated nasal application of mupirocin ointment would decrease the odds of S. aureus nasal colonization in 100 HELP/PSI patients over an 8-month period. A 5-day course of study drug was given monthly, and colonization was assessed at baseline and 1 month after each treatment. S. aureus infection was a secondary outcome., Results: In repeated-measures analysis, mupirocin reduced the odds of monthly S. aureus nasal colonization by 83% compared with placebo [adjusted odds ratio (ORadj) = 0.17; P < 0.0001]. Subjects colonized at study entry had a 91% reduction in subsequent colonization (ORadj = 0.09; P < 0.0001). Mupirocin also suppressed S. aureus colonization in subjects not colonized at baseline (ORadj = 0.23; P = 0.006). There was no difference in infection rates between the mupirocin and placebo groups (hazard ratio = 0.49, P = 0.29)., Conclusions: Monthly application of nasal mupirocin significantly decreased S. aureus colonization in HIV patients in residential drug rehabilitation. Monthly mupirocin application has a potential role in long-term care settings or in HIV-positive patients with high rates of S. aureus colonization and infection.