Ethical considerations for HIV remission clinical research involving participants diagnosed during acute HIV infection.

HIV remission clinical researchers are increasingly seeking study participants who are diagnosed and treated during acute HIV infection-the brief period between infection and the point when the body creates detectable HIV antibodies. This earliest stage of infection is often marked by flu-like illness and may be an especially tumultuous period of confusion, guilt, anger, and uncertainty. Such experiences may present added ethical challenges for HIV research recruitment, participation, and retention. The purpose of this paper is to identify potential ethical challenges associated with involving acutely diagnosed people living with HIV in remission research and considerations for how to mitigate them. We identify three domains of potential ethical concern for clinicians, researchers, and ethics committee members to consider: 1) Recruitment and informed consent; (2) Transmission risks and partner protection; and (3) Ancillary and continuing care. We discuss each of these domains with the aim of inspiring further work to advance the ethical conduct of HIV remission research. For example, experiences of confusion and uncertainty regarding illness and diagnosis during acute HIV infection may complicate informed consent procedures in studies that seek to recruit directly after diagnosis. To address this, it may be appropriate to use staged re-consent procedures or comprehension assessment. Responsible conduct of research requires a broad understanding of acute HIV infection that encompasses its biomedical, psychological, social, and behavioral dimensions. We argue that the lived experience of acute HIV infection may introduce ethical concerns that researchers and reviewers should address during study design and ethical approval.

Moral practices shaping HIV disclosure among young gay and bisexual men living with HIV in the context of biomedical advance.

Biomedical advances in diagnostics, treatment and prevention increase the means available to reduce HIV transmission risk. Subsequent shifts in HIV status disclosure obligation and ethics may impact how those living with HIV view, enact and experience disclosure. We analysed focus group and interview data to explore how these changes are reflected in disclosure decision-making to sexual partners among young gay and bisexual men living with HIV in the USA. Three interrelated themes were identified: engaging with partners' varying HIV knowledge; attribution of blame; and negotiating disclosure-related harms. Participants experienced blame from partners that questioned the timing of HIV testing, status disclosure and sex events without regards for viral suppression or use of pre-exposure prophylaxis. Substantial HIV stigma was described in response to disclosure, mitigated in some cases by partners' higher HIV knowledge. Overall, an uneven diffusion of HIV treatment and prevention knowledge and continuing HIV stigma seemed to limit the translation of biomedical advances into improved disclosure experiences. Our findings suggest that young gay and bisexual men living with HIV may continue to perform much of the moral labour involved in disclosure by managing others' reactions, correcting inaccurate sexual health information, and negotiating the risks of disclosure-related harm.

Ethics of pursuing targets in public health: the case of voluntary medical male circumcision for HIV-prevention programs in Kenya.

The use of targets to direct public health programmes, particularly in global initiatives, has become widely accepted and commonplace. This paper is an ethical analysis of the utilisation of targets in global public health using our fieldwork on and experiences with voluntary medical male circumcision (VMMC) initiatives in Kenya. Among the many countries involved in VMMC for HIV prevention, Kenya is considered a success story, its programmes having medically circumcised nearly 2 million men since 2007. We describe ethically problematic practices in Kenyan VMMC programmes revealed by our fieldwork, how the problems are related to the pursuit of targets and discuss possible approaches to their management. Although the establishment and pursuit of targets in public health can have many benefits, assessments of target-driven programmes tend to focus on quantifiable outcomes rather than the processes by which the outcomes are obtained. However, in order to speak more robustly about programmatic 'success', and to maintain community trust, it is vital to ethically evaluate how a public health initiative is actually implemented in the pursuit of its targets.

Consent Challenges and Psychosocial Distress in the Scale-up of Voluntary Medical Male Circumcision Among Adolescents in Western Kenya.

In priority sub-Saharan African countries, on the ground observations suggest that the success of voluntary medical male circumcision (VMMC) programs should not be based solely on numbers of males circumcised. We identify gaps in the consent process and poor psychosocial outcomes among a key target group: male adolescents. We assessed compliance with consent and assent requirements for VMMC in western Kenya among males aged 15-19 (N = 1939). We also examined differences in quality of life, depression, and anticipated HIV stigma between uncircumcised and circumcised adolescents. A substantial proportion reported receiving VMMC services as minors without parent/guardian consent. In addition, uncircumcised males were significantly more likely than their circumcised peers to have poor quality of life and symptoms of depression. Careful monitoring of male adolescents' well-being is needed in large-scale VMMC programs. There is also urgent need for research to identify effective strategies to address gaps in the delivery of VMMC services.

Ethics of treatment interruption trials in HIV cure research: addressing the conundrum of risk/benefit assessment.

Though antiretroviral therapy is the standard of care for people living with HIV, its treatment limitations, burdens, stigma and costs lead to continued interest in HIV cure research. Early-phase cure trials, particularly those that include analytic treatment interruption (ATI), involve uncertain and potentially high risk, with minimal chance of clinical benefit. Some question whether such trials should be offered, given the risk/benefit imbalance, and whether those who choose to participate are acting rationally. We address these questions through a longitudinal decision-making study nested in a Thai acute HIV research cohort.In-depth interviews revealed central themes about decisions to join. Participants felt they possessed an important identity as members of the acute cohort, viewing their bodies as uniquely suited to both testing and potentially benefiting from HIV cure approaches. While acknowledging risks of ATI, most perceived they were given an opportunity to interrupt treatment, to test their own bodies and increase normalcy in a safe, highly monitored circumstance. They were motivated by potential benefits to themselves, the investigators and larger acute cohort, and others with HIV. They believed their own trial experiences and being able to give back to the community were sufficient to offset participation risks.These decisions were driven by the specific circumstances experienced by our participants. Judging risk/benefit ratios without appreciating these lived experiences can lead to false determinations of irrational decision- making. While this does not minimise vital oversight considerations about risk reduction and protection from harm, it argues for inclusion of a more participant-centered approach.

Implications of prioritizing HIV cure: new momentum to overcome old challenges in HIV.

BACKGROUND: Curing HIV is a new strategic priority for several major AIDS organizations. In step with this new priority, HIV cure research and related programs are advancing in low, middle, and high-income country settings. This HIV cure momentum may influence existing HIV programs and research priorities. DISCUSSION: Despite the early stage of ongoing HIV cure efforts, these changes have directly influenced HIV research funding priorities, pilot programs, and HIV messaging. The building momentum to cure HIV infection may synergize with strategic priorities to better identify adults and infants with very early HIV infection. Although HIV cure represents a new goal, many existing programs and research techniques can be repurposed towards an HIV cure. HIV messages focused on engaging communities towards an HIV cure need to be careful to promote ARV adherence and retention within the HIV continuum of care. An increased emphasis within the AIDS field on finding an HIV cure has several important implications. Strengthening connections between HIV cure research and other areas of HIV research may help to catalyze research and facilitate implementation in the future.

Healing Without Waging War: Beyond Military Metaphors in Medicine and HIV Cure Research.

Military metaphors are pervasive in biomedicine, including HIV research. Rooted in the mind set that regards pathogens as enemies to be defeated, terms such as "shock and kill" have become widely accepted idioms within HIV cure research. Such language and symbolism must be critically examined as they may be especially problematic when used to express scientific ideas within emerging health-related fields. In this article, philosophical analysis and an interdisciplinary literature review utilizing key texts from sociology, anthropology, history, and Chinese and African studies were conducted to investigate the current proliferation of military metaphors. We found the use of these metaphors to be ironic, unfortunate, and unnecessary. To overcome military metaphors we propose to (1) give them less aggressive meanings, and/or (2) replace them with more peaceful metaphors. Building on previous authors' work, we argue for the increased use of "journey" (and related) metaphors as meaningful, cross-culturally appropriate alternatives to military metaphors.

Plasmon-induced optical anisotropy in hybrid graphene-metal nanoparticle systems.

Hybrid plasmonic metal-graphene systems are emerging as a class of optical metamaterials that facilitate strong light-matter interactions and are of potential importance for hot carrier graphene-based light harvesting and active plasmonic applications. Here we use femtosecond pump-probe measurements to study the near-field interaction between graphene and plasmonic gold nanodisk resonators. By selectively probing the plasmon-induced hot carrier dynamics in samples with tailored graphene-gold interfaces, we show that plasmon-induced hot carrier generation in the graphene is dominated by direct photoexcitation with minimal contribution from charge transfer from the gold. The strong near-field interaction manifests as an unexpected and long-lived extrinsic optical anisotropy. The observations are explained by the action of highly localized plasmon-induced hot carriers in the graphene on the subresonant polarizability of the disk resonator. Because localized hot carrier generation in graphene can be exploited to drive electrical currents, plasmonic metal-graphene nanostructures present opportunities for novel hot carrier device concepts.

Probing the dielectric response of graphene via dual-band plasmonic nanoresonators.

In this article, we use optical transmission spectroscopy to measure the changes in the resonance features of a Au plasmonic nanoresonator array consisting of concentric ring/disc cavity elements, when graphene is introduced as an encapsulating medium. We show that by using finite element modelling to best reproduce our experimental results the dielectric response of the graphene film can be determined. We discuss the potential of such structures for chemical sensing applications.

A review of public health, social and ethical implications of voluntary medical male circumcision programs for HIV prevention in sub-Saharan Africa.

Ideally, the benefits of public health interventions should outweigh any associated harms, burdens, and adverse unintended consequences. The intended benefit of voluntary medical male circumcision (VMMC) programs in eastern and southern Africa (ESA) is the reduction of HIV infections. We review the literature for evidence of reductions in HIV incidence, evaluate the extent to which decreases in HIV incidence can be reasonably attributed to VMMC programs, and summarize social harms and ethical concerns associated with these programs. Review findings suggest that HIV incidence had been declining across ESA since before the large-scale rollout of VMMC as a public health intervention, and that this decline may be due to the combined effects of HIV prevention and treatment interventions, such as expanded antiretroviral therapy. The independent effect of VMMC programs in reducing HIV infections at the population level remains unknown. On the other hand, VMMC-associated evidence is increasing for the existence of negative social impacts such as stigmatization and/or discrimination, and ethically problematic practices, including lack of informed consent. We conclude that the relationship between the benefits and burdens of VMMC programs may be more unfavorable than what has been commonly suggested by proponents of global VMMC campaigns.

Acceptability of a HIV self-testing program among people who use illicit drugs.

BACKGROUND: People who use illicit drugs (PWUD) remain at significantly elevated risk for HIV infection and continue to have very low testing rates. HIV self-testing (HIVST) has been shown to be acceptable among many high-risk populations, but less is known about PWUD. METHODS: From May-June 2021, a HIVST program was implemented at a syringe services program (SSP) in Louisville, Kentucky. PWUD were given the option to privately self-test at the SSP or take the test home and follow-up with study staff. Primary outcomes were acceptability, ease of use, usability, reasons for self-testing, testing location, frequency of future testing, and preference for future testing location. RESULTS: Among 230 study participants, 77% reported high acceptability (i.e., the HIVST kits made them feel much more able to keep track of their HIV status compared to standard testing methods). Virtually all (97.4%) reported the test kits were very easy to use. Problems while using the HIVST kits were rare (range 1.3-3.0%). The most common reasons for testing were a desire to know their status (85.2%), the test was free (37%), and the short duration for results (30.9%). Testing primarily occurred onsite (87.8%). The majority (83%) reported they would use the HIVST kits at least every six months if made available through the health department and would prefer to test at home (71.7%). Multivariate analyses found that awareness of and intention to use pre-exposure prophylaxis (PrEP) were significantly associated with high acceptability and testing onsite. CONCLUSION: Study participants found HIVST to be acceptable and very easy to use. The multivariate findings suggest HIVST interventions should be packaged with PrEP interventions and harm reduction programs.

The Ethics of Stigma in Medical Male Circumcision Initiatives Involving Adolescents in Sub-Saharan Africa.

Ongoing global efforts to circumcise adolescent and adult males to reduce their risk of acquiring HIV constitute the largest public health prevention initiative, using surgical means, in human history. Voluntary medical male circumcision (VMMC) programs in Africa have significantly altered social norms related to male circumcision among previously non-circumcising groups and groups that have practiced traditional (non-medical) circumcision. One consequence of this change is the stigmatization of males who, for whatever reason, remain uncircumcised. This paper discusses the ethics of stigma with regard to uncircumcised adolescent males in global VMMC programs, particularly in certain recruitment, demand creation and social norm interventions. Grounded in our own experiences gained while conducting HIV-related ethics research with adolescents in Kenya, we argue that use of explicit or implicit stigma to increase the number of VMMC volunteers is unethical from a public health ethics perspective, particularly in campaigns that leverage social norms of masculinity. Ongoing global efforts to circumcise adolescent and adult males to reduce their risk of acquiring HIV constitute the largest public health prevention initiative, using surgical means, in human history. VMMC programs in Africa have significantly altered social norms related to male circumcision among previously non-circumcising groups and groups that have practiced traditional (non-medical) circumcision. One consequence of this change is the stigmatization of males who, for whatever reason, remain uncircumcised. This paper discusses the ethics of stigma with regard to uncircumcised adolescent males in global VMMC programs, particularly in certain recruitment, demand creation and social norm interventions. Grounded in our own experiences gained while conducting HIV-related ethics research with adolescents in Kenya, we argue that use of explicit or implicit stigma to increase the number of VMMC volunteers is unethical from a public health ethics perspective, particularly in campaigns that leverage social norms of masculinity.

Indirect Benefits in HIV Cure Clinical Research: A Qualitative Analysis.

Currently, much of early phase HIV cure research involves unknown and potentially serious risks, with little or no chance of direct health benefits. During informed consent, researchers emphasize this lack of personal medical benefit to minimize misconceptions that undermine genuine consent. We explored participants' and researchers' perspectives on HIV cure clinical research participation and its potential benefits. We conducted semistructured interviews with 17 HIV cure research participants and nine researchers in North Carolina, USA. We analyzed interviews to identify participant experience-related themes. We were particularly interested in indirect benefits, such as psychological support or improved care. We also assessed five consent documents for benefit/risk-related language. Research participants were male, with a median age of 50 (range: 28-62); most were non-Hispanic white (15/17) and men who have sex with men (13/17). All 17 trial participants found research participation meaningful and beneficial. Reported benefits included improved healthcare (16/17), HIV knowledge (13/17), intimate relationships (10/17), and positive behaviors (6/17). In addition, all participants described psychological benefits, including increased positive outlook, improved sense of purpose, emotional support, and enriched self-image. Participants reported risks such as quality of life concerns, uncomfortable procedures (e.g., leukapheresis), latency reversal, and HIV status disclosure. While the consent documents included discussion of these and other risks, they did not mention potential indirect benefits. Individuals involved in HIV clinical research have recognized participant psychological, social, and behavioral benefits. We recommend that researchers and institutional review boards consider these benefits for inclusion during risk/benefit assessments, consent procedures, and other discussions with prospective participants.

Voluntary medical male circumcision for HIV prevention among adolescents in Kenya: Unintended consequences of pursuing service-delivery targets.

INTRODUCTION: Voluntary medical male circumcision (VMMC) provides significant reductions in the risk of female-to-male HIV transmission. Since 2007, VMMC has been a key component of the United States President's Emergency Plan for AIDS Relief's (PEPFAR) strategy to mitigate the HIV epidemic in countries with high HIV prevalence and low circumcision rates. To ensure intended effects, PEPFAR sets ambitious annual circumcision targets and provides funding to implementation partners to deliver local VMMC services. In Kenya to date, 1.9 million males have been circumcised; in 2017, 60% of circumcisions were among 10-14-year-olds. We conducted a qualitative field study to learn more about VMMC program implementation in Kenya. METHODS AND RESULTS: The study setting was a region in Kenya with high HIV prevalence and low male circumcision rates. From March 2017 through April 2018, we carried out in-depth interviews with 29 VMMC stakeholders, including "mobilizers", HIV counselors, clinical providers, schoolteachers, and policy professionals. Additionally, we undertook observation sessions at 14 VMMC clinics while services were provided and observed mobilization activities at 13 community venues including, two schools, four public marketplaces, two fishing villages, and five inland villages. Analysis of interview transcripts and observation field notes revealed multiple unintended consequences linked to the pursuit of targets. Ebbs and flows in the availability of school-age youths together with the drive to meet targets may result in increased burdens on clinics, long waits for care, potentially misleading mobilization practices, and deviations from the standard of care. CONCLUSION: Our findings indicate shortcomings in the quality of procedures in VMMC programs in a low-resource setting, and more importantly, that the pursuit of ambitious public health targets may lead to compromised service delivery and protocol adherence. There is a need to develop improved or alternative systems to balance the goal of increasing service uptake with the responsible conduct of VMMC.

The Role of Inclusion Benefits in Ethics Committee Assessment of Research Studies.

The relationship between risks and benefits is central to the ethics of research involving human participants. Traditionally, to be ethically justifiable, risks should be reasonable in relation to anticipated benefits (if any) to subjects and to the potential social benefits resulting from research. This calculus is being further complicated by findings from an increasing number of social science studies that reveal that prospective and actual research participants frequently describe various types of inclusion benefits (for example, personal benefits such as access to or improved health care, increased knowledge about their disease or condition, and greater solidarity with the local community) as important to them. What is the ethical significance of such inclusion benefits, particularly those nonmedical in nature, for research ethics committees' risk-benefit assessment of research studies? We argue that, unless participants are clearly mistaken in their perceptions, ethics committees should take these types of inclusion benefits into account, and we suggest a few ways this might look in practice.

If We Build It, Will They Come? Perceptions of HIV Cure-Related Research by People Living with HIV in Four U.S. Cities: A Qualitative Focus Group Study.

Global interest and investment in the search for an HIV cure has increased. Research has focused on what experts refer to as a sterilizing or eradicating cure, where HIV is eliminated from the body, and on what is often called a functional cure, where HIV remains, kept durably suppressed in the absence of antiretroviral treatment and therapy (ART). Many believe that a functional cure is likely to be found first. HIV cure studies will require active participation by people living with HIV (PLWHIV). Their desires and perceptions will be important to effectively recruit study participants and for the uptake of any future strategy that demonstrates safety and efficacy. The perspectives of PLWHIV are essential to advancing HIV cure research, and they should be taken into consideration as biomedical research advances. We conducted 10 focus groups in four U.S. cities, eliciting perspectives of PLWHIV on HIV cure and cure research. Most participants conceived of a cure as eradicating, and felt favorably toward it. In addition to the physical benefits of a potential cure, participants valued the possible de-stigmatization related to no longer living with HIV, liberation from concerns about transmitting HIV, and freedom from the burden of daily medication. Many participants did not regard a functional cure as an improvement over controlling HIV through ART, were distrustful about viral rebound potential, and noted concerns about medical complications and accompanying psychological distress. Some felt that the risks of HIV cure research were not worth taking. Many were skeptical about science's ability to eliminate HIV from the body.

Plasmon induced thermoelectric effect in graphene.

Graphene has emerged as a promising material for optoelectronics due to its potential for ultrafast and broad-band photodetection. The photoresponse of graphene junctions is characterized by two competing photocurrent generation mechanisms: a conventional photovoltaic effect and a more dominant hot-carrier-assisted photothermoelectric (PTE) effect. The PTE effect is understood to rely on variations in the Seebeck coefficient through the graphene doping profile. A second PTE effect can occur across a homogeneous graphene channel in the presence of an electronic temperature gradient. Here, we study the latter effect facilitated by strongly localised plasmonic heating of graphene carriers in the presence of nanostructured electrical contacts resulting in electronic temperatures of the order of 2000 K. At certain conditions, the plasmon-induced PTE photocurrent contribution can be isolated. In this regime, the device effectively operates as a sensitive electronic thermometer and as such represents an enabling technology for development of hot carrier based plasmonic devices.