HIV risk behavior profiles among men who have sex with men interested in donating blood: Findings from the Assessing Donor Variability and New Concepts in Eligibility study.

BACKGROUND: Individual risk assessment allows donors to be evaluated based on their own behaviors. Study objectives were to assess human immunodeficiency virus (HIV) risk behaviors in men who have sex with men (MSM) and estimate the proportion of the study population who would not be deferred for higher risk HIV sexual behaviors. STUDY DESIGN AND METHODS: Cross-sectional survey and biomarker assessment were conducted in eight U.S. cities. Participants were sexually active MSM interested in blood donation aged 18-39 years, assigned male sex at birth. Participants completed surveys during two study visits to define eligibility, and self-reported sexual and HIV prevention behaviors. Blood was drawn at study visit 1 and tested for HIV and the presence of tenofovir, one of the drugs in oral HIV pre-exposure prophylaxis (PrEP). Associations were assessed between HIV infection status or HIV PrEP use and behaviors, including sex partners, new partners, and anal sex. RESULTS: A total of 1566 MSM completed the visit 1 questionnaire and blood draw and 1197 completed the visit 2 questionnaire. Among 1562 persons without HIV, 789 (50.4%) were not taking PrEP. Of those not taking PrEP, 66.2% reported one sexual partner or no anal sex and 69% reported no new sexual partners or no anal sex with a new partner in the past 3 months. CONCLUSION: The study found that questions were able to identify sexually active, HIV-negative MSM who report lower risk sexual behaviors. About a quarter of enrolled study participants would be potentially eligible blood donors using individual risk assessment questions.

Urgent Need for Next-Generation COVID-19 Vaccines.

This Viewpoint argues that the development of a distinctly improved generation of SARS-CoV-2 vaccines is paramount to offering a greater breadth and depth of protection for a longer duration against COVID-19 disease.

Clinical Development Strategies and Considerations for Zika Vaccine Licensure.

The Zika outbreak that began in 2015 has spread from Brazil to countries across the Western Hemisphere including the United States, presenting global public health challenges that call for the expedited development and availability of preventive vaccines to protect against Zika virus disease. While the general principles guiding the nonclinical and clinical development for Zika vaccines are the same as those of other preventive vaccines, unique considerations apply, in particular if development occurs during a public health emergency. Furthermore, incomplete information about the pathogenesis of Zika virus disease and the mechanism by which candidate preventive vaccines potentially may confer protection presents additional challenges to their clinical development. Nevertheless, definition of clinical development strategies to enable sound regulatory assessment, with a goal toward licensure is critical for these products. This article will provide an overview of the regulatory considerations for the clinical development and licensure of Zika vaccine candidates including a discussion of clinical study designs, approaches to demonstrate vaccine effectiveness, and regulatory pathways to licensure.

Maintaining a Safe Blood Supply in an Era of Emerging Pathogens.

Coming shortly after outbreaks of dengue and chikungunya virus in related locations, the recent outbreak of Zika virus in the southern part of the western hemisphere is yet another reminder that infectious pathogens continue to emerge rapidly and can adversely affect public health, including the safety of the blood supply. In response to Zika virus, public health measures that rely largely on donor deferral and sourcing of blood from non-outbreak areas until a blood donor screening test becomes available have been implemented to address the safety of the blood supply in the United States. However, a more universal approach to ensuring blood safety in the setting of rapidly emerging infectious diseases is needed.

Screening of Blood Donations for Zika Virus Infection - Puerto Rico, April 3-June 11, 2016.

Transfusion-transmitted infections have been documented for several arboviruses, including West Nile and dengue viruses (1). Zika virus, a flavivirus transmitted primarily by Aedes aegypti mosquitoes that has been identified as a cause of congenital microcephaly and other serious brain defects (2), became recognized as a potential threat to blood safety after reports from a 2013-2014 outbreak in French Polynesia. Blood safety concerns were based on very high infection incidence in the population at large during epidemics, the high percentage of persons with asymptomatic infection, the high proportion of blood donations with evidence of Zika virus nucleic acid upon retrospective testing, and an estimated 7-10-day period of viremia (3). At least one instance of transfusion transmission of Zika virus has been documented in Brazil after the virus emerged there, likely in 2014 (4). Rapid epidemic spread has followed to other areas of the Americas, including Puerto Rico.

Iron out for nontransfused thalassemia.

Individuals with ß-thalassemia intermedia and hemoglobinopathies of equivalent severity who are infrequently or never transfused can still develop serious complications of iron overload. Taher et al report the first 1-year, randomized, double-blind, placebo-controlled trial of oral iron chelation therapy with deferasirox in this population.

Biological therapies need definitive randomized controlled clinical trials.

Adequate and well-controlled clinical trials remain critical tools for helping to bring benefit to patients in medical need.

Benefit-risk assessment of Covid-19 vaccine, MRNA (MRNA-1273) for males age 18-64 years.

Since the authorization of the Moderna mRNA COVID-19 vaccine, real-world evidence has indicated its effectiveness in preventing COVID-19 cases. However, increased cases of mRNA vaccine-associated myocarditis/pericarditis have been reported, predominantly in young adults and adolescents. The Food and Drug Administration conducted a benefit-risk assessment to inform the review of the Biologics License Application for use of the Moderna vaccine among individuals ages 18 and older. We modeled the benefit-risk per million individuals who receive two complete doses of the vaccine. Benefit endpoints were vaccine-preventable COVID-19 cases, hospitalizations, intensive care unit (ICU) admissions, and deaths. The risk endpoints were vaccine-related myocarditis/pericarditis cases, hospitalizations, ICU admissions, and deaths. The analysis was conducted on the age-stratified male population due to data signals and previous work showing males to be the main risk group. We constructed six scenarios to evaluate the impact of uncertainty associated with pandemic dynamics, vaccine effectiveness (VE) against novel variants, and rates of vaccine-associated myocarditis/pericarditis cases on the model results. For our most likely scenario, we assumed the US COVID-19 incidence was for the week of December 25, 2021, with a VE of 30% against cases and 72% against hospitalization with the Omicron-dominant strain. Our source for estimating vaccine-attributable myocarditis/pericarditis rates was FDA's CBER Biologics Effectiveness and Safety (BEST) System databases. Overall, our results supported the conclusion that the benefits of the vaccine outweigh its risks. Remarkably, we predicted vaccinating one million 18-25 year-old males would prevent 82,484 cases, 4,766 hospitalizations, 1,144 ICU admissions, and 51 deaths due to COVID-19, comparing to 128 vaccine-attributable myocarditis/pericarditis cases, 110 hospitalizations, zero ICU admissions, and zero deaths. Uncertainties in the pandemic trajectory, effectiveness of vaccine against novel variants, and vaccine-attributable myocarditis/pericarditis rate are important limitations of our analysis. Also, the model does not evaluate potential long-term adverse effects due to either COVID-19 or vaccine-attributable myocarditis/pericarditis.

Benefit-risk assessment of COVID-19 vaccine, mRNA (Comirnaty) for age 16-29 years.

Since authorization of the Pfizer-BioNTech COVID-19 Vaccine, mRNA (Comirnaty), real-world evidence has indicated the vaccines are effective in preventing COVID-19 cases and related hospitalizations and deaths. However, increased cases of myocarditis/pericarditis have been reported in the United States associated with vaccination, particularly in adolescents and young adults. FDA conducted a benefit-risk assessment to determine whether the benefits of vaccination outweigh the risks among various age (16-17, 18-24, 25-29) and sex (M/F) subgroups being considered for approved use of the vaccine. We conducted a simulation study with sensitivity analysis of the benefits and risks of the vaccine across possible pandemic scenarios. The model results show benefits outweigh the risks for all scenarios including the high-risk subgroup, males 16-17 years old. Our worst-case scenario used sex and age subgroup-specific incidences for COVID-19 cases (47-98 per million per day) and hospitalizations (1-4 per million per day) which are the US COVID-19 incidences as of July 10, 2021, vaccine efficacy of 70% against COVID-19 cases and 80% against hospitalization, and unlikely, pessimistic, non-zero vaccine-attributable myocarditis death rate. For males 16-17 years old, the model predicts prevented COVID cases, hospitalizations, ICUs, and deaths of 13577, 127, 41, and 1, respectively; while the predicted ranges for excess myocarditis/pericarditis cases, hospitalizations, and deaths attributable to the vaccine are [98-196], [98-196], and 0, respectively, for the worst-case scenario. Considering the different clinical implications of hospitalization due to COVID-19 infection versus vaccine-attributable myocarditis/pericarditis cases, we determine the benefits still outweigh the risks even for this high-risk subgroup. Our results demonstrate that the benefits of the vaccine outweigh its risks for all age and sex subgroups we analyze in this study. Uncertainties exist in this assessment as both benefits and risks of vaccination may change with the continuing evolution of the pandemic.

Transfusion and chelation practices in sickle cell disease: a regional perspective.

Although most common in tropical regions, population migration has meant that sickle cell disease is now one of the most prevalent genetic diseases worldwide. The issues and challenges faced by physicians and patients have been discussed by an international group of experts representing 4 key regions: the USA, Europe, Latin America, and the Middle East/Africa. Conclusive evidence to support the use of transfusion therapy for the prevention of stroke has resulted in key changes to patient management in all regions, and increasing numbers of patients are benefiting from this management approach. However, it is apparent that transfusion therapy is still under-utilized, largely due to concerns over iron overload, alloimmunization, limited blood supplies, and, sometimes, due to parental refusal. Once transfused, assessment and management of body iron levels can be poor, particularly in patients who are intermittently transfused. Compliance with chelation therapy regimens is a significant challenge, but new therapeutic options are likely to overcome some of the current barriers. Key requirements in all regions were considered to be the following: to provide greater physician, patient, and family education; to ensure effective transition from pediatric to adult care; and to establish national guidelines in order to ensure best practice is consistently applied.