Breaking barriers: Scientific contributions in virology from women in low- and middle-income countries

The advancement of science has been a collective effort and benefits from a diversity of views and gender representation. However, support for and recognition of women in science is often insufficient. Despite historically being marginalized by the scientific community, research by women has advanced the field of virology, from the discovery of rotavirus and isolation of human immunodeficiency virus (HIV) to a vaccine for polio and the initial description of a virus’ ability to cause cancer. Although women in science, technology, engineering, and mathematics (STEM) fields are continuing to share their diverse wealth of knowledge and innovation, even today many are under-recognized and under-supported in low- and middle-income countries (LMICs). This review will highlight women in virology from LMICs in Africa, Asia, and Latin America where the barriers to scientific education and achievement for women can be far greater than in high income countries. Despite these barriers, the women we profile below have made important contributions to translational virology. We hope this review will contribute to the global expansion of efforts to provide improved access to and retention in scientific careers for women

Protease inhibitors effectively block cell-to-cell spread of HIV-1 between T cells

Background; The Human Immunodeficiency Virus type-1 (HIV-1) spreads by cell-free diffusion and by direct cell-to-cell transfer, the latter being a significantly more efficient mode of transmission. Recently it has been suggested that cell-to-cell spread may permit ongoing virus replication in the presence of antiretroviral therapy (ART) based on studies performed using Reverse Transcriptase Inhibitors (RTIs). Protease Inhibitors (PIs) constitute an important component of ART; however whether this class of inhibitors can suppress cell-to-cell transfer of HIV-1 is unexplored. Here we have evaluated the inhibitory effect of PIs during cell-to-cell spread of HIV-1 between T lymphocytes. Results; Using quantitative assays in cell line and primary cell systems that directly measure the early steps of HIV-1 infection we find that the PIs Lopinavir and Darunavir are equally potent against both cell-free and cell-to-cell spread of HIV-1. We further show that a protease resistant mutant maintains its resistant phenotype during cell-to-cell spread and is transmitted more efficiently than wild-type virus in the presence of drug. By contrast we find that T cell-T cell spread of HIV-1 is 4–20 fold more resistant to inhibition by the RTIs Nevirapine, Zidovudine and Tenofovir. Notably, varying the ratio of infected and uninfected cells in co-culture impacted on the degree of inhibition, indicating that the relative efficacy of ART is dependent on the multiplicity of infection. Conclusions; we conclude that if the variable effects of antiviral drugs on cell-to-cell virus dissemination of HIV-1 do indeed impact on viral replication and maintenance of viral reservoirs this is likely to be influenced by the antiviral drug class, since PIs appear particularly effective against both modes of HIV-1 spread. Keywords: HIV-1; Virological synapse; Cell-cell spread; Protease inhibitor; AR

Creating a best practice template for participant communication plans in global health clinical studies

Background Clinical trial participants have a right to be informed throughout the entire process of human subject research. As part of this pillar of research ethics, participants and other stakeholders should be made aware of research findings after a trial has been completed. Though participants have both a right, and a desire to be informed of research outcomes, studies show that they rarely receive communication about study findings. Our aim was (1) to understand what, if any, role communication plans play in current global health clinical research protocols and (2) to use our findings to develop a communication plan template tailored to clinical research carried out in low-and-middle-income countries (LMIC) while minimizing colonial assumptions. While the template was drafted in the LMIC context, the principles are universally applicable and should be considered best practices for all global health clinical trials. Methods We carried out a mixed-method study over a period of 6 months to understand the role of communication with study participants and other stakeholders in clinical trials. The semiquantitative analysis included mining publicly available clinical trial protocols for communication-related language. Qualitative interviews (n = 7) were used to gather knowledge and insight from clinical trial experts to inform the development of a communication plan template. Results None of the 48 mined clinical trial protocols included a communication plan. Of the 48, 21% (n = 21) protocols included communication-related language, and 10% (n = 5) described plans to share trial results with participants. Conclusion The use of communication plans in global health clinical trials is lacking. To our knowledge, this is the first in-depth analysis of communication plans in clinical trials to date. We recommend that researchers utilize the developed communication plan template throughout the entire research process to ensure a human-centered approach to participant communication. This communication plan should apply to all phases of a research trial, with a particular emphasis on plans to share results in an accessible and engaging manner once the trial has been completed

Monkeypox Emergency: Urgent Questions and Perspectives

Amidst the COVID-19 pandemic, we now face another public health emergency in the form of monkeypox virus. As of August 1, the Centers for Disease Control and Prevention report over 23,000 cases in 80 countries. An inclusive and global collaborative effort to understand the biology, evolution, and spread of the virus as well as commitment to vaccine equity will be critical toward containing this outbreak. We share the voices of leading experts in this space on what they see as the most pressing questions and directions for the community

Hospitalization risk among patients with Mpox infection—a propensity score matched analysis

Background: Monkeypox (Mpox) is a reemerging, neglected viral disease. By May 2023, worldwide Mpox cases surpassed 87,000. Predictive factors for hospitalization with Mpox are lacking. Objective: We aim to compare clinical characteristics and outcomes in hospitalized and nonhospitalized patients with Mpox infection. Design: A multicenter retrospective case-control cohort of patients with Mpox infection. Methods: We performed a propensity score match analysis from a global health network (TrinetX). We compare clinical characteristics and outcomes between hospitalized and nonhospitalized patients with Mpox. Results: Of 1477 patients, 6% were hospitalized, 52% required an ED visit, and 29% received treatment at urgent care. After propensity score matching, 80 patients remained in each group. Hospitalizations were more common among Black persons (51% versus 33%, p = 0.01), people with HIV (50% versus 20%, p < 0.0001), and those with proctitis (44% versus 12.5%, p < 0.001). Conclusion: Independent predictive factors of hospitalization in our cohort for Mpox included people who are Black with a diagnosis of HIV, severe proctitis, pain requiring opioids, and elevated lactate dehydrogenase. Greater recognition of factors associated with increased risk of Mpox severity and hospitalization is paramount.Dr. Boghuma K. Titanji is funded by the NIH BIRCWH program and Emory CFAR grant P30AI050509)

Development and Application of a Broadly Sensitive Dried-Blood-Spot-Based Genotyping Assay for Global Surveillance of HIV-1 Drug Resistance ▿

As antiretroviral therapy (ART) is scaled up in resource-limited countries, surveillance for HIV drug resistance (DR) is vital to ensure sustained effectiveness of first-line ART. We have developed and applied a broadly sensitive dried-blood-spot (DBS)-based genotyping assay for surveillance of HIV-1 DR in international settings. In 2005 and 2006, 171 DBS samples were collected under field conditions from newly diagnosed HIV-1-infected individuals from Malawi (n = 58), Tanzania (n = 60), and China (n =53). In addition, 30 DBS and 40 plasma specimens collected from ART patients in China and Cameroon, respectively, were also tested. Of the 171 DBS analyzed at the protease and RT regions, 149 (87.1%) could be genotyped, including 49 (81.7%) from Tanzania, 47 (88.7%) from China, and 53 (91.4%) from Malawi. Among the 70 ART patient samples analyzed, 100% (30/30) of the Chinese DBS and 90% (36/40) of the Cameroonian plasma specimens were genotyped, including 8 samples with a viral load of <400 copies/ml. The results of phylogenetic analyses indicated that the subtype, circulating recombinant form (CRF), and unique recombinant form (URF) distribution was as follows: 73 strains were subtype C (34%), 37 were subtype B (17.2%), 24 each were CRF01_AE or CRF02_AG (11.2% each), 22 were subtype A1 (10.2%), and 9 were unclassifiable (UC) (4.2%). The remaining samples were minor strains comprised of 6 that were CRF07_BC (2.8%), 5 that were CRF10_CD (2.3%), 3 each that were URF_A1C and CRF08_BC (1.4%), 2 each that were G, URF_BC, and URF_D/UC (0.9%), and 1 each that were subtype F1, subtype F2, and URF_A1D (0.5%). Our results indicate that this broadly sensitive genotyping assay can be used to genotype DBS collected from areas with diverse HIV-1 group M subtypes and CRFs. Thus, the assay is likely to become a useful screening tool in the global resistance surveillance and monitoring of HIV-1 where multiple subtypes and CRFs are found