A case cluster demonstrating the relationship between HLA concordance and virologic and disease outcomes in human immunodeficiency virus infection

AbstractWe present a detailed analysis of sexual HIV transmission from one source partner to two recipients. The HLA haplotypes between the source partner and one recipient were very similar with 7 out of 8 HLA alleles from four loci (HLA A, B, C and DRB) shared, while the other recipient shared only one allele. The immunologic outcomes between the two recipients differed dramatically, despite the absence of apparent virologic differences in their inoculums. We suggest that non-viral factors, which might be related to differences in the HLA profile, played a role in determining different CD4+ T-cells dynamics for these two recipients

Considerations for designing and implementing combination HIV cure trials: findings from a qualitative in-depth interview study in the United States

Background: An increasing number of HIV cure trials involve combining multiple potentially curative interventions. Until now, considerations for designing and implementing complex combination HIV cure trials have not been thoroughly considered. Methods: We used a purposive method to select key informants for our study. Informants included biomedical HIV cure researchers, regulators, policy makers, bioethicists, and community members. We used in-depth interviews to generate ethical and practical considerations to guide the design and implementation of combination HIV cure research. We analyzed the qualitative data using conventional content analysis focused on inductive reasoning. Results: We interviewed 11 biomedical researchers, 4 community members, 2 regulators, 1 policy researcher, and 1 bioethicist. Informants generated considerations for designing and implementing combination interventions towards an HIV cure, focused on ethical aspects, as well as considerations to guide trial design, benefit/risk determinations, regulatory requirements, prioritization and sequencing and timing of interventions, among others. Informants also provided considerations related to combining specific HIV cure research modalities, such as broadly neutralizing antibodies (bNAbs), cell and gene modification products, latency-reversing agents and immune-based interventions. Finally, informants provided suggestions to ensure meaningful therapeutic improvements over standard antiretroviral therapy, overcome challenges of designing combination approaches, and engage communities around combination HIV cure research. Conclusion: The increasing number of combination HIV cure trials brings with them a host of ethical and practical challenges. We hope our paper will inform meaningful stakeholder dialogue around the use of combinatorial HIV cure research approaches. To protect the public trust in HIV cure research, considerations should be periodically revisited and updated with key stakeholder input as the science continues to advance

Ethical and practical considerations for interventional HIV cure-related research at the end-of-life: A qualitative study with key stakeholders in the United States

Background A unique window of opportunity currently exists to generate ethical and practical considerations presented by interventional HIV cure-related research at the end-of-life (EOL). Because participants would enroll in these studies for almost completely altruistic reasons, they are owed the highest ethical standards, safeguards, and protections. This qualitative empirical ethics study sought to identify ethical and practical considerations for interventional HIV cure-related research at the EOL. Methods and findings We conducted 20 in-depth interviews and three virtual focus groups (N = 36) with four key stakeholder groups in the United States: 1) bioethicists, 2) people with HIV, 3) HIV care providers, and 4) HIV cure researchers. This study produced six key themes to guide the ethical implementation of interventional HIV cure-related research at the EOL: 1) all stakeholder groups supported this research conditioned upon a clearly delineated respect for participant contribution and autonomy, participant understanding and comprehension of the risks associated with the specific intervention(s) to be tested, and broad community support for testing of the proposed intervention(s); 2) to ensure acceptable benefit-risk profiles, researchers should focus on limiting the risks of unintended effects and minimizing undue pain and suffering at the EOL; 3) only well-vetted interventions that are supported by solid pre-clinical data should be tested in the EOL translational research model; 4) the informed consent process must be robust and include process consent; 5) research protocols should be flexible and adopt a patient/participant centered approach to minimize burdens and ensure their overall comfort and safety; and 6) a participant’s next-of-kin/loved ones should be a major focus of EOL research but only if the participant consents to such involvement

Attitudes and perceptions of next-of-kin/loved ones toward end-of-life HIV cure-related research: A qualitative focus group study in Southern California

As end-of-life (EOL) HIV cure-related research expands, understanding perspectives of participants’ next-of-kin (NOK) is critical to maintaining ethical study conduct. We conducted two small focus groups and two one-on-one interviews using focus group guides with the NOK of Last Gift study participants at the University of California, San Diego (UCSD). Participating NOK included six individuals (n = 5 male and n = 1 female), including a grandmother, grandfather, partner, spouse, and two close friends. Researchers double-coded the transcripts manually for overarching themes and sub-themes using an inductive approach. We identified six key themes: 1) NOK had an accurate, positive understanding of the Last Gift clinical study; 2) NOK felt the study was conducted ethically; 3) Perceived benefits for NOK included support navigating the dying/grieving process and personal growth; 4) Perceived drawbacks included increased sadness, emotional stress, conflicted wishes between NOK and study participants, and concerns around potential invasiveness of study procedures at the EOL; 5) NOK expressed pride in loved ones’ altruism; and 6) NOK provided suggestions to improve the Last Gift study, including better communication between staff and themselves. These findings provide a framework for ethical implementation of future EOL HIV cure-related research involving NOK

Ethical and practical considerations for HIV cure-related research at the end-of-life: a qualitative interview and focus group study in the United States

Background: One of the next frontiers in HIV research is focused on finding a cure. A new priority includes people with HIV (PWH) with non-AIDS terminal illnesses who are willing to donate their bodies at the end-of-life (EOL) to advance the search towards an HIV cure. We endeavored to understand perceptions of this research and to identify ethical and practical considerations relevant to implementing it. Methods: We conducted 20 in-depth interviews and 3 virtual focus groups among four types of key stakeholders in the United States (PWH, biomedical HIV cure researchers, HIV clinicians, and bioethicists) to obtain triangulated viewpoints because little was known about the ethics of this topic. Each group was queried as to ethical considerations, safeguards, and protections for conducting HIV cure-related research at the EOL to ensure this research remains acceptable. Results: All four key stakeholder groups generally supported HIV cure-related research conducted at the EOL because of the history of altruism within the PWH community and the potential for substantial scientific knowledge to be gained. Our informants expressed that: (1) Strong stakeholder and community involvement are integral to the ethical and effective implementation, as well as the social acceptability of this research; (2) PWH approaching the EOL should not inherently be considered a vulnerable class and their autonomy must be respected when choosing to participate in HIV cure-related research at the EOL; (3) Greater diversity among study participants, as well as multi-disciplinary research teams, is necessitated by HIV cure-related research at the EOL; (4) The sensitive nature of this research warrants robust oversight to ensure a favorable risk/benefit balance and to minimize the possibility of therapeutic misconception or undue influence; and (5) Research protocols should remain flexible to accommodate participants’ comfort and needs at the EOL. Conclusion: Because of the ethical issues presented by HIV cure-related research at the EOL, robust ethical safeguards are of utmost importance. The proposed ethical and practical considerations presented herein is a first step in determining the best way to maximize this research’s impact and social value. More much inquiry will need to be directed towards understanding context-specific and cultural considerations for implementing EOL HIV cure research in diverse settings

The spatial distribution of HO2in an atmospheric pressure plasma jet investigated by cavity ring-down spectroscopy

Cold atmospheric pressure plasma jets make important contributions to a range of fields, such as materials processing and plasma medicine. In order to optimise the effect of those plasma sources, a detailed understanding of the chemical reaction networks is pivotal. However, the small diameter of plasma jets makes diagnostics challenging. A promising approach to obtain absolute number densities is the utilisation of cavity-enhanced absorption spectroscopy methods, by which line-of-sight averaged densities are determined. Here, we present first measurements on how the spatial distribution of HO2 in the effluent of a cold atmospheric pressure plasma jet can be obtained by cavity ring-down spectroscopy in an efficient way. Instead of recording fully wavelength resolved spectra, we will demonstrate that it is sufficient to measure the absorption coefficient at two wavelengths, corresponding to the laser being on and off the molecular resonance. By sampling the effluent from the 1.6 mm diameter nozzle in the radial direction at various axial positions, we determined that the distances over which the HO2 density was distributed were (3.9 ± 0.5) mm and (6.7 ± 0.1) mm at a distance of 2 mm and 10 mm below the nozzle of the plasma jet, respectively. We performed an Abel inversion in order to obtain the spatial distribution of HO2 that is presented along the symmetry axis of the effluent. Based on that localised density, which was (4.8 ± 0.6) ⋅ 1014 cm-3 at the maximum, we will discuss the importance of the plasma zone for the production of HO2