Monkeypox, a zoonosis caused by the orthopox monkeypox virus (MPXV) that is endemic to Central and West Africa, was previously linked to sporadic outbreaks and rare, travel-associated cases. An ...outbreak of monkeypox in 2022 has spurred a public health emergency of international concern, and this outbreak is unprecedented in terms of its scale and epidemiology. The outbreak has been focused overwhelmingly in men who have sex with men; however, the trajectory of the outbreak remains uncertain, with spread now being reported in women and children. The mortality has been low (<1%), yet the morbidity is high. Vaccines and oral antiviral agents that have been developed to protect against smallpox are available for use against monkeypox. However, the supply has been unable to match the demand during the outbreak. Passive antibody-based therapies, such as hyperimmune globulin (HIG), monoclonal antibodies, and convalescent plasma (CP), have been used against a diverse array of infectious diseases, culminating in their extensive use during the COVID-19 pandemic. Passive antibody-based therapies could play a role in the treatment of monkeypox, either as a temporizing role amid a shortfall in vaccines and antivirals or a complementary role to direct-acting antivirals. Drawing on the collective experience to date, there are regulatory, administrative, and logistical challenges to the implementation of antibody-based therapies. Their efficacy is contingent upon early administration and the presence of high-titer antibodies against the targeted pathogen. Research is needed to address questions pertaining to how to qualify HIG and CP and to determine their relative efficacy against MPXV, compared to antecedent therapies and preventative strategies.
Monkeypox is an infection caused by the monkeypox virus (MPXV). The clinical findings in monkeypox include fever and rash. Historically, most cases of human monkeypox were reported in Africa. This changed in 2022, with a massive escalation in the number of cases across multiple countries, mainly affecting men who have sex with men. Although vaccines and oral antiviral medications are available for the treatment of monkeypox, their supply has been overwhelmed by the unprecedented number of cases. Antibody-based therapies (ABTs) have long been used to treat infectious diseases. They are produced in a laboratory or from plasma that has been collected from individuals who have recovered from an infection or have been vaccinated against that infection (in this case, monkeypox). ABTs could play a role in the treatment of monkeypox, either while awaiting oral medications or as a complementary treatment for patients that are at risk of severe disease.
The "All of Us" Research Program. Reply Denny, Joshua C; Devaney, Stephanie A; Gebo, Kelly A
The New England journal of medicine,
11/2019, Volume:
381, Issue:
19
Journal Article
The “All of Us” Research Program Sullivan, Frank; McKinstry, Brian; Vasishta, Shobna ...
The New England journal of medicine,
11/2019, Volume:
381, Issue:
19
Journal Article
Peer reviewed
Open access
To the Editor:
Denny and colleagues (Aug. 15 issue)
1
describe the progress of the All of Us Research Program. In Scotland, which has a population of 5.43 million, a patient registry
2
is achieving ...some of the advantages envisaged by All of Us. The Scottish Health Research Register (SHARE) began accessing data from electronic health records (EHRs) in 2011 and obtaining genomic data (from “leftover” blood samples) in 2013; it now includes data on 270,604 persons who are 11 years of age or older (as of August 2019) and has collected 97,642 blood samples. The means of recruitment include the SHARE . . .
Background. Most persons with human immunodeficiency virus (HIV) infection in the United States present to care with advanced disease, and many patients discontinue therapy prematurely. We sought to ...evaluate sex and racial/ethnic disparities in life-years lost as a result of risk behavior, late presentation, and early discontinuation of HIV care, and we compared these survival losses for HIV-infected persons with losses attributable to high-risk behavior and HIV disease itself. Methods. With use of a state-transition model of HIV disease, we simulated cohorts of HIV-infected persons and compared them with uninfected individuals who had similar demographic characteristics. We estimated non-HIV-related mortality with use of risk-adjusted standardized mortality ratios, as well as years of life lost because of late presentation and early discontinuation of antiretroviral therapy (ART) for HIV infection. Data from the national HIV Research Network, stratified by sex and race/ethnicity, were used for estimating CD4+cell counts at ART initiation. Results. For HIV-uninfected persons in the United States who have risk profiles similar to those of individuals with HIV infection, the projected life expectancy, starting at 33 years of age, was 34.58 years, compared with 42.91 years for the general US population. Those with HIV infection lost an additional 11.92 years of life if they received HIV care concordant with guidelines; late treatment initiation resulted in 2.60 additional years of life lost, whereas premature ART discontinuation led to 0.70 more years of life lost. Losses from late initiation and early discontinuation were greatest for Hispanic individuals (3.90 years). Conclusions. The high-risk profile of HIV-infected persons, HIV infection itself, as well as late initiation and early discontinuation of care, all lead to substantial decreases in life expectancy. Survival disparities resulting from late initiation and early discontinuation of therapy are most pronounced for Hispanic HIV-infected men and women. Interventions focused on risk behaviors, as well as on earlier linkage to and better retention in care, will lead to improved survival for HIV-infected persons in the United States.
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Abstract
Coronavirus disease 2019 (COVID-19) convalescent plasma (CCP) is a safe and effective treatment for COVID-19 in immunocompromised (IC) patients. IC patients have a higher risk of persistent ...infection, severe disease, and death from COVID-19. Despite the continued clinical use of CCP to treat IC patients, the optimal dose, frequency/schedule, and duration of CCP treatment has yet to be determined, and related best practices guidelines are lacking. A group of individuals with expertise spanning infectious diseases, virology and transfusion medicine was assembled to render an expert opinion statement pertaining to the use of CCP for IC patients. For optimal effect, CCP should be recently and locally collected to match circulating variant. CCP should be considered for the treatment of IC patients with acute and protracted COVID-19; dosage depends on clinical setting (acute vs protracted COVID-19). CCP containing high-titer severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) antibodies, retains activity against circulating SARS-CoV-2 variants, which have otherwise rendered monoclonal antibodies ineffective.
This viewpoint offers expert guidance for the use of coronavirus disease 2019 (COVID-19) convalescent plasma (CCP) to treat immunocompromised patients with acute or protracted COVID-19, addressing indications, dosage, frequency/schedule, and duration of treatment, along with the evidence and associated challenges of use.
BACKGROUND:For optimal clinical benefit, HIV-infected patients should receive periodic outpatient care indefinitely. However, initially establishing HIV care and subsequent retention in care are ...problematic. This study examines establishment, retention, and loss to follow-up (LTFU) in a large multi-site cohort over a 2–8 year period.
METHODS:Medical record data were reviewed for 22,984 adult HIV patients receiving care at 12 clinics in the HIV Research Network between 2001 and 2009. Three dichotomous outcome measures were based on each patientʼs history of outpatient visits. Establishment reflects whether the patient made outpatient visits for longer than 6 months after initial enrollment. The retention measure reflects whether the patient had at least 2 outpatient visits separated by 90 days in each year in care. LTFU reflects whether the patient had no outpatient visits for more than 12 months without returning. Multiple logistic regression examined demographic and clinical correlates of each outcome and the combined outcome of meeting all 3 measures.
RESULTS:Overall, 21.7% of patients never established HIV care after an initial visit. Among established patients, 57.4% did not meet the retention criterion in all years, and 34.9% were LTFU. Only 20.4% of all patients met all 3 criteria. The odds of successfully meeting all 3 criteria were higher for women, for older patients, for Hispanics compared with whites, and for those with CD4 levels ≤50 cells per cubic millimeter.
CONCLUSIONS:These data highlight the need to improve establishment and retention in HIV care.
INTRODUCTION:Gaps in Medicaid enrollment may affect HIV outcomes. We evaluated factors associated with Medicaid enrollment gaps and their effect on viral suppression (VS) within the HIV Research ...Network.
METHODS:We used a combined data set with Medicaid enrollment files from 2006 to 2010 and HIV Research Network demographic and clinical data. A gap was defined as ≥1 month without Medicaid and gap length was determined. We used multivariable logistic regression to determine factors associated with a gap and multivariable logistic regression with generalized estimated equations to evaluate factors associated with VS after gap.
RESULTS:Of 5836 participants, the majority were male, of black race, and aged 25–50 years. More than half had a gap in Medicaid. Factors associated with a gap included male sex adjusted odds ratio (aOR) 1.79, (1.53, 2.08) and younger age (aORs ranging from 1.50 to 4.13 comparing younger age groups to age >50, P < 0.05 for all). About a quarter of gaps had VS information before and after gap. Of those, 53.7% had VS both before and after gap and 25.8% were unsuppressed both before and after gap. The strongest association with VS after gap was VS before gap aOR 15.76 (10.48, 23.69). Transition into Ryan White HIV/AIDS Program coverage during Medicaid gaps was common (28% of all transitions).
CONCLUSIONS:Gaps in Medicaid enrollment were common and many individuals with pre-gap VS maintained VS after gap, possibly due to accessing other sources of antiretroviral therapy coverage. Implementing initiatives to maintain Medicaid enrollment and to expedite Medicaid reenrollment and having alternate resources available in gaps are important to ensure continuous antiretroviral therapy to optimize HIV outcomes.
INTRODUCTION:Hospitalization rates for comorbid conditions among persons living with HIV in the current highly active antiretroviral therapy era are unknown.
METHODS:Hospitalization data from 2001 to ...2008 were obtained on 11,645 adults receiving longitudinal HIV care at 4 geographically diverse US HIV clinics within the HIV Research Network. Modified clinical classification software from the Agency for Healthcare Research and Quality assigned primary ICD-9 codes into diagnostic categories. Analysis was performed with repeated measures negative binomial regression.
RESULTS:During 2001 to 2008, the rate of AIDS-defining illness (ADI) hospitalizations declined from 6.7 to 2.7 per 100 person-years, incidence rate ratio per year, 0.89 (0.87, 0.91). Among the other diagnostic categories with average rates >2 per 100 person-years, cardiovascular hospitalizations increased over time 1.07 (1.03, 1.11), whereas non–AIDS-defining infection 0.98 (0.96, 1.00), psychiatric 0.96 (0.93, 1.00), and gastrointestinal/liver 0.96 (0.92, 1.00) were slightly decreasing or stable. Although less frequent overall, renal and pulmonary admissions also increased over time in univariate and multivariate analyses. Of all diagnostic categories, ADI admissions had the longest mean length of stay, 10.5 days.
DISCUSSION:ADI hospitalizations have continued to decline in recent years but are still relatively frequent and potentially costly given long lengths of stay. Increases or stability in the rates of chronic end-organ disease admissions imply a need for broader medical knowledge among individual clinicians and/or teams who care for persons living with HIV and a need for long-term access to medications for these conditions.
Context: A large proportion of people with human immunodeficiency virus (HIV) infection enter care late in the HIV disease course. Late entry can increase expenditures for care. Objective: To ...estimate direct medical care expenditures for HIV patients as a function of disease status at initial presentation to care. Late entry is defined as initial CD4 test result ≤200 cells/mm³, intermediate entry as initial CD4 counts >200, and ≤500 cells/mm³; and early entry as initial CD4 count >500. Patients: The study included 8348 patients who received HIV primary care and who were newly enrolled between 2000 and 2006 at one of 10 HIV clinics participating in the HIV Research Network. Design: We reviewed medical record data from 2000 to 2007. We estimated costs per outpatient visit and inpatient day, and monthly medication costs (antiretroviral and opportunistic illness prophylaxis). We multiplied unit costs by utilization measures to estimate expenditures for inpatient days, outpatient visits, HIV medications, and laboratory tests. We analyzed the association between cumulative expenditures and initial CD4 count, stratified by years in care. Results: Late entrants comprised 43.1% of new patients. The number of years receiving care after enrollment did not differ significantly across initial CD4 groups. Mean cumulative treatment expenditures ranged from $27,275 to $61,615 higher for late than early presenters. After 7 to 8 years in care, the difference was still substantial. Conclusions: Patients who enter medical care late in their HIV disease have substantially higher direct medical treatment expenditures than those who enter at earlier stages. Successful efforts to link patients with medical care earlier in the disease course may yield cost savings.
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To investigate trends, patient characteristics, and survival associated with AIDS-defining cancer (ADC) and non-AIDS defining cancer (NADC) in the HAART era.
Retrospective analysis of all incident ...malignancies occurring in 1996-2005 among 2566 patients in an urban HIV clinic.
Clinical profiles of NADC were compared with ADC and the general cohort. Incidence was examined by Poisson analysis. Standardized incidence ratios (SIR) compared cancer risk with that in the general population. Survival was analyzed by Kaplan-Meier and Cox proportional hazards models.
Between 1996 and 2005, 138 ADC and 115 NADC were diagnosed. ADC rates decreased from 12.5 to 3.5 cases/1000 person-years (P < 0.001 for trend) while NADC rates increased from 3.9 to 7.1 cases/1000 person-years (P = 0.13 for trend). Incidence of the most common NADC was higher than expected, including cancers of the lung n = 29; SIR, 5.5; 95% confidence interval (CI), 3.7-8.0, liver (n = 13, SIR, 16.5; 95% CI, 8.8-28.2), anus (n = 10; SIR, 39.0; 95% CI, 18.7-71.7), head and neck (n = 14; SIR, 5.1; 95% CI, 2.8-8.6), and Hodgkin's lymphoma (n = 8; SIR, 9.8; 95% CI, 4.2-19.2). Survival after cancer diagnosis did not differ between ADC and NADC. Advanced age was associated with NADC (P < 0.01 for trend) and increased mortality in ADC (age > or = 50 years adjusted hazard ratio, 2.21; 95% CI, 1.00-4.89).
Rates of ADC decreased while NADC increased within this cohort. Several NADC occurred at rates significantly higher than expected. Screening and suspicion for NADC should increase in care for HIV-infected patients.
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