Benign ethnic neutropenia (BEN) is defined as a neutrophil count of <1.5×109 cells/L in healthy individuals and is more common in populations of certain ethnicities, e.g. African or Middle Eastern ethnicity. Neutrophil values are commonly included in eligibility criteria for research participation, but little is known about the relationship between BEN, HIV acquisition, and the occurrence of adverse events during clinical trials. We investigated these relationships using data from an HIV vaccine efficacy trial of healthy adults from 5 South African sites. We analysed data from the double-blind, placebo-controlled, randomized trial HVTN 503, and its follow-on study HVTN 503-S to assess the prevalence of BEN, its association with HIV infection, and adverse event reporting. These data were then compared with a time- and age-matched, non-pregnant cohort from the National Health and Nutrition Examination Survey (NHANES) conducted between 2007–2008 in the United States (US). The 739 South African participants had a median age of 22.0 years (interquartile range = 20–26) and 56% (n = 412) were male. Amongst the US cohort of 845 participants, the median age was 26 (IQR: 21–30) and the majority (54%, 457/745) were also male. BEN was present at enrolment in 7.0% (n = 52) of South African participants (6% in the placebo group versus 8% in the vaccine group); 81% (n = 42) of those with BEN were male. Pretoria North had the highest prevalence of BEN (11.6%, 5/43), while Cape Town had the lowest (0.7%, 1/152). Participants with BEN had a lower median neutrophil count (1.3 vs. 3.2x109 cells/L; p<0.001) and BMI (20.8 vs. 22.3 kg/m2; p<0.001) when compared to those without BEN. A greater proportion of Black South Africans had neutrophil counts <1.5×109 cells/L compared to US non-Hispanic Whites from the NHANES cohort (7% [52/739] vs. 0.6% [3/540]; p<0.001). BEN did not increase the odds for HIV infection (adjusted odds ratio [aOR]: 1.364, 95% confidence interval [95% CI]: 0.625–2.976; p = 0.4351). However, female gender (aOR: 1.947, 95% CI: 1.265–2.996; p = 0.0025) and cannabis use (aOR: 2.192, 95% CI: 1.126–4.266; p = 0.0209) increased the odds of HIV acquisition. The incidence rates of adverse events were similar between participants in the placebo group with BEN, and those without: 12.1 (95% CI: 7.3–20.1) vs. 16.5 (95% CI: 14.6–18.7; p = 0.06) events per 100 person-years (py) were noted in the infections and infestations system organ class, respectively. The vaccine group had an event incidence rate of 19.7 (95% CI: 13.3–29.2) vs. 14.8 (95% CI: 13.0–16.8; p = 0.07) events per 100py in the group with, and without BEN, respectively. BEN is more prevalent in Black South Africans compared to US Non-Hispanic Whites. Our data do not support excluding populations from HIV vaccine trials because of BEN. BEN was not associated with increased risk for HIV infection or Adverse events on a vaccine trial. Predictors of HIV infection risk were females and cannabis use, underlying the continued importance of prevention programmes in focusing on these populations.
Although chloroquine and hydroxychloroquine have not yet been shown to be safe or effective for the treatment or prevention of COVID-19, regulatory agencies in some countries have authorised their use in Coronavirus disease 2019 (COVID-19) due to the lack of available interventions. Several large clinical trials are currently underway to investigate these agents as potential therapeutic options for COVID-19. Previous research against similar pathogens that cause severe acute respiratory syndrome and Middle East respiratory syndrome has identified chloroquine and hydroxychloroquine as possible antiviral candidates against SARS-CoV-2. Despite promising pre-clinical evidence, data have thus far failed to confirm their efficacy, and recent studies suggest potential dose-related cardiotoxicity and mortality. Close monitoring for cardiac conduction abnormalities is advised with higher-than-approved doses. Additional, robust evidence from randomised controlled trials and meta-analyses are required to make informed risk-benefit assessments. Finally, the off-label prescription of these agents should be judiciously considered, and any such use should be conducted within clinical trials, or under the Monitored Emergency Use of Unregistered and Investigational Interventions framework.
Although chloroquine and hydroxychloroquine have not yet been shown to be safe or effective for the treatment or prevention of COVID-19, regulatory agencies in some countries have authorised their use in Coronavirus disease 2019 (COVID-19) due to the lack of available interventions. Several large clinical trials are currently underway to investigate these agents as potential therapeutic options for COVID-19. Previous research against similar pathogens that cause severe acute respiratory syndrome and Middle East respiratory syndrome has identified chloroquine and hydroxychloroquine as possible antiviral candidates against SARS-CoV-2. Despite promising pre-clinical evidence, data have thus far failed to confirm their efficacy, and recent studies suggest potential dose-related cardiotoxicity and mortality. Close monitoring for cardiac conduction abnormalities is advised with higher-than-approved doses. Additional, robust evidence from randomised controlled trials and meta-analyses are required to make informed risk-benefit assessments. Finally, the off-label prescription of these agents should be judiciously considered, and any such use should be conducted within clinical trials, or under the Monitored Emergency Use of Unregistered and Investigational Interventions framework.
scite is a Brooklyn-based organization that helps researchers better discover and understand research articles through Smart Citations–citations that display the context of the citation and describe whether the article provides supporting or contrasting evidence. scite is used by students and researchers from around the world and is funded in part by the National Science Foundation and the National Institute on Drug Abuse of the National Institutes of Health.
hi@scite.ai
10624 S. Eastern Ave., Ste. A-614
Henderson, NV 89052, USA
Copyright © 2024 scite LLC. All rights reserved.
Made with 💙 for researchers
Part of the Research Solutions Family.