Engaging transgender women in HIV research in South Africa.

The Botshelo Ba Trans study was the first HIV bio-behavioral survey conducted with transgender women in South Africa. Engaging research with marginalized communities requires clear points of entry, reference points for understanding the internal culture, and establishing trust and understanding. The community-based participatory research approach guided the development and implementation of this study. We conducted a rapid qualitative and pre-surveillance formative assessment between August 2017 to January 2018 and a bio-behavioral survey between July 2018 and March 2019. At the start, a Steering Committee, comprising primarily of transgender women, was established and subsequently provided substantial input into the mixed methods study conducted in Buffalo City, Cape Town, and Johannesburg. Key to the study's success was building trust and establishing ownership of the survey by transgender women recognized as expert knowledge holders. Thus, a community-based participatory research-informed approach enhanced the validity of the data and ensured that we addressed relevant issues.

Improving the informed consent process among HIV-infected undisclosed minors participating in a biomedical research: insights from the multicentre nutritional SNACS study in Senegal.

OBJECTIVES: Providing research information in a manner accessible to minors participating in biomedical research is a major challenge. Guidance is dramatically lacking regarding best practices for seeking informed consent among undisclosed minors enrolled in HIV-related research. We implemented an improved informed consent process (IICP) and identified factors associated with understanding of the information presented to HIV-infected minors prior to their enrolment in a study. METHODS: We enrolled study participants attending 12 paediatric HIV clinics in Senegal. Children ≥7 years were provided with standardised research information using the IICP, which involves viewing a video and taking part in extended group discussions. Understanding was assessed by seven basic questions scored 1 or 2 points, with a maximum score of 11 points. A score of 9 or more points was defined as satisfactory understanding. Factors associated with understanding were identified using a stepwise logistic regression model. RESULTS: Overall, 112 children, with a median age of 12.9 years (IQR: 10.2-15.0), participated in the IICP, of whom 37% were HIV disclosed. 71% achieved a satisfactory understanding score and all gave consent to participate in the research. HIV-disclosed children were more likely to demonstrate satisfactory understanding than undisclosed children (aOR = 3.2, 95% CI: 1.1-9.6). Age, study setting and education level were not associated with satisfactory understanding. CONCLUSION: These findings provide practical guidance for the development of improved and friendly informed consent processes in research involving minors. The implementation of the paediatric HIV research agenda will require a standardised and operational definition of informed consent, integrating the issue of HIV disclosure.

OBJECTIFS: Fournir des informations sur la recherche d'une manière accessible aux mineurs participant à la recherche biomédicale est un défi majeur. Les guidances font cruellement défaut en ce qui concerne les meilleures pratiques pour obtenir le consentement éclairé des mineurs non dévoilés, inscrits dans des recherches sur le VIH. Nous avons mis en place un processus de consentement éclairé amélioré (PCEA) et identifié les facteurs associés à la compréhension des informations présentées aux mineurs infectés par le VIH avant leur inscription à une étude. MÉTHODES: Nous avons recruté des participants à l'étude dans 12 cliniques pédiatriques de traitement du VIH au Sénégal. Les enfants de 7 ans et plus ont reçu des informations de recherche standardisées à l'aide du PCEA, qui consiste à visionner une vidéo et à participer à des discussions de groupe prolongées. La compréhension a été évaluée par 7 questions de base notées 1 ou 2 points, avec un score maximum de 11 points. Un score de 9 points ou plus a été défini comme une compréhension satisfaisante. Les facteurs associés à la compréhension ont été identifiés à l'aide d'un modèle de régression logistique par étapes. RÉSULTATS: Au total, 112 enfants âgés de 12,9 ans en moyenne (IQR: 10,2-15,0) ont participé au PCEA, dont 37% avaient leur statut VIH dévoilé. 71% ont obtenu un score de compréhension satisfaisant et tous ont consenti à participer à la recherche. Les enfants avec un statut VIH dévoilé étaient plus susceptibles de démontrer une compréhension satisfaisante que ceux avec un statut non dévoilé (aOR: 3,2; IC95%: 1,1-9,6). L'âge, le cadre de l'étude et le niveau d'éducation n'étaient pas associés à une compréhension satisfaisante. CONCLUSION: Ces résultats fournissent des guidances pratiques pour la mise au point de processus de consentement éclairé améliorés et conviviaux dans la recherche impliquant des mineurs. La mise en œuvre du programme de recherche pédiatrique sur le VIH nécessitera une définition normalisée et opérationnelle du consentement éclairé, intégrant la question de la révélation du VIH.

Usage of the Terms Prostitution, Sex Work, Transactional Sex, and Survival Sex: Their Utility in HIV Prevention Research.

This article considers the terms prostitution, sex work, transactional sex, and survival sex, the logic of their deployment and utility to research concerned with people who are paid for sex, and HIV. The various names for paid sex in HIV research are invested in strategically differentiated positionings of people who receive payment and emphasize varying degrees of choice. The terminologies that seek to distinguish a range of economically motivated paid sex practices from sex work are characterized by an emphasis on the local and the particular, efforts to evade the stigma attached to the labels sex worker and prostitute, and an analytic prioritizing of culture. This works to bestow cultural legitimacy on some locally specific forms of paid sex and positions those practices as artifacts of culture rather than economy. This article contends that, in HIV research in particular, it is necessary to be cognizant of ways the deployment of alternative paid sex categories relocates and reinscribes stigma elsewhere. While local identity categories may be appropriate for program implementation, a global category is necessary for planning and funding purposes and offers a purview beyond that of isolated local phenomena. We argue that "sex work" is the most useful global term for use in research into economically motivated paid sex and HIV, primarily because it positions paid sex as a matter of labor, not culture or morality.

Navigating Opportunities, Learning and Potential Threats: Mentee Perspectives on Mentoring in HIV Research.

Increasing the diversity of the HIV research workforce remains a priority for research and funding organizations in the US. Mentorship is a vital component for early-career investigators, especially for underrepresented racial/ethnic and sexual minority HIV investigators. These investigators face unique social and structural challenges to developing and fostering mentorship relationships, as well as building a solid foundation for a successful career in HIV research. This article provides a perspective from four Black early-career investigators, supplemented with comments from 15 underrepresented investigators in the US, as they reflect on their needs, challenges, contributions, and successes in finding the right mentor and mentorship environment, balancing the opportunities for, and "threats" to success, as well as providing mentorship to other underrepresented and aspiring HIV investigators. Mentorship programs must address these needs and challenges while building on the strengths of underrepresented HIV investigators in order to improve recruitment, retention and ultimately the pipeline of these researchers.

Embedding HIV Mentoring Programs in HIV Research Networks.

Responding to the demands of the HIV/AIDS epidemic necessitates a diverse scientific and clinical workforce trained in applying interdisciplinary research approaches to address the epidemic domestically and internationally. Ensuring diversity in our workforce requires concerted efforts. Yet, the majority of graduate and post-graduate programs are ill-equipped to provide this type of training. Research networks, the HPTN, HVTN, CFAR and ATN, are uniquely positioned to implement interdisciplinary mentoring programs and all four have done so. We describe these programs, the nuts and bolts of program implementation and efforts to recruit and retain diversity scholars. We outline some inherent challenges such as competing demands for network resources or tension in aligning scholars' research agenda with that of the networks. We argue that the benefits to be gained from continuing these programs far outweigh their costs and that these programs are an essential component of a comprehensive strategy for developing the future HIV research workforce.

Future HIV Mentoring Programs to Enhance Diversity.

This paper proposes a general template to guide future mentoring program development addressing: (i) considerations to ensure an adequate research workforce; (ii) key guidelines and principles of mentoring; and (iii) use of a logic model to develop program milestones, outcomes and evaluation. We focus on these areas to guide and inform the most effective mentoring program components, which we find to be more helpful than identifying specific features and ingredients. Although the focus is on the development of a new generation of investigators from diverse backgrounds, this template may also apply to mentoring programs for other investigators and for disciplines beyond HIV.

Decision making for invasive and non-invasive optional procedures within an acute HIV research cohort in Bangkok.

Clinical research regularly includes required, nontherapeutic procedures to answer research questions. Optional procedures usually offer minimal or no personal benefit and may involve harms and burdens. Members from the Bangkok SEARCH010/RV254 HIV research cohort of individuals acutely HIV-infected are recruited to six optional procedures varying in invasiveness: leukapheresis, genital secretions collection, lumbar puncture, brain MRI/MRS/DTI, colon biopsy, and lymph node biopsy. We surveyed cohort members about their first recruitment for each procedure to examine factors associated with decision making and attitudes about compensation. 406 members (68%) completed the survey. Reported procedure participation ranged from 71% (MRI) to 27% (lymph node biopsy). Respondents underwent 0-6 procedure types (median 3). Ordinal regression indicated that lower perceived HIV impact and HIV remission trial participation were associated with more procedures completed. Reports of decision difficulty varied, and feeling pressured by research staff was low overall. Notably, those who declined procedures and those who underwent more invasive procedures reported greater decision difficulty and perceived pressure. Most respondents felt compensation amounts were appropriate, although opinions differed by procedure, and for some procedures, between people who agreed and declined. There is limited literature regarding consent to and attitudes about optional research procedures. Researchers must consider how to best support voluntary decisions for procedures with little personal benefit, particularly in lower-income or marginalized populations. In this longitudinal research cohort, perceived pressure to participate may be a concern, although our finding of variation in participation rates corresponding to invasiveness is reassuring. Data from different research contexts would provide important comparators.

When Ethics and the Law Collide: A Multicenter Demonstration Cohort Study of Pre-Exposure Prophylaxis Provision to Adolescent Men Who Have Sex With Men and Transgender Women in Brazil.

PURPOSE: To explore legal and ethical challenges related to adolescents' participation in human immunodeficiency virus (HIV) research that may affect their best interests. METHODS: We analyzed the ethical principles and legal aspects of the participation of 15-17-year-old men who have sex with men and transgender women in the pre-exposure prophylaxis (PrEP) 1519 study, a PrEP demonstration cohort study in three Brazilian cities. The analyses of ethics review committees' (ERCs) evaluations and court decisions followed ethical and human rights principles. An HIV vulnerability score was created, and descriptive statistics and multivariate logistic regression were performed using data from 347 participants. RESULTS: The ERCs evaluated the benefits and risks of research participation, all finding that the benefits outweighed the risks. ERCs deferred responsibility for decisions about waiving parental consent to the judiciary. State courts reached different decisions about waiving parental consent, reflecting variation in recognition of adolescents' evolving capacities and the adolescent as a subject of sexual rights and the primary agent capable of deciding on their health and best interests. The most vulnerable adolescent participants were found in sites where the blanket waiver was in place. DISCUSSION: Judicializing the ethical review process is detrimental to fulfilling the ethical principle of justice and vulnerable adolescents' access to health research. ERCs must be sufficiently independent and autonomous and have the capacity to respect, protect, and help fulfill the rights of participants while ensuring the generation of adequate evidence to inform public health practice.

Assessing Facilitator Fidelity to Principles of Public Deliberation: Tutorial.

Public deliberation, or deliberative democracy, is a method used to elicit informed perspectives and justifiable solutions to ethically fraught or contentious issues that affect multiple stakeholder groups with conflicting interests. Deliberative events bring together stakeholders (deliberants) who are provided with empirical evidence on the central issue or concern and then asked to discuss the evidence, consider the issue from a societal perspective, and collectively work toward a justifiable resolution. There is increasing interest in this method, which warrants clear guidance for evaluating the quality of its use in research. Most of the existing literature on measuring deliberation quality emphasizes the quality of deliberants' inputs (eg, engagement and evidence of compromise) during deliberative sessions. Fewer researchers have framed quality in terms of facilitator inputs, and these researchers tend to examine inputs that are consistent with generic group processes. The theory, process, and purpose of public deliberation, however, are distinct from those of focus groups or other group-based discussions and warrant a mechanism for measuring quality in terms of facilitator fidelity to the principles and processes of deliberative democracy. In our public deliberation on ethical conflicts in minor consent for biomedical HIV prevention research, we assessed facilitator fidelity to these principles and processes because we believe that such assessments serve as a component of a comprehensive evaluation of overall deliberation quality. We examined verbatim facilitator remarks in the deliberation transcripts and determined whether they aligned with the 6 principles of public deliberation: equal participation, respect for the opinions of others, adoption of a societal perspective, reasoned justification of ideas, expression of diverse opinions, and compromise or movement toward consensus. In this tutorial, we describe the development of a blueprint to guide researchers in assessing facilitator fidelity, share 3 templates that will assist them in the task, and describe the results of our assessment of facilitator fidelity in 1 of the 4 sites in which we conducted deliberations.

Perceptions of Undergraduates and Mentors on the Appropriateness, Acceptability, and Feasibility of the HEPI-TUITAH Micro-Research Approach to HIV Training in Uganda.

Purpose: To evaluate the perceptions of undergraduates and mentors on the appropriateness, acceptability, and feasibility of a mentored seed-grant (micro-research) by Health Professions Education Partnership Initiative - Transforming Ugandan Institutions Training Against HIV/AIDS (HEPI-TUITAH) program on HIV training in Uganda. Methods: We conducted a cross-sectional descriptive qualitative study with focus groups, on HIV micro-research training, with undergraduate health professions students and faculty mentors across three partner institutions in rural Uganda. Results: A total of 24 students and 13 mentors (5-8 per group) took part in the focus group discussions. Most participants stated that the HEPI-TUITAH micro-research program was acceptable, appropriate and feasible for health professions undergraduate students. The interprofessional education approach of bringing together students from different programs and years of study was valuable especially for peer mentorship. There was a need to provide for institution-based training in addition to the centrally organized training for the benefit of all the team members. Participants also noted a need for the program to find a way of providing the students with data collection experience even with the COVID-19 pandemic situation. Conclusion: The HEPI-TUITAH micro-research program was perceived as acceptable, appropriate, and feasible for health professions undergraduate students. It also promoted teamwork and academic collaboration. Provision for institution-based micro-research training activities and data collection experiences for the undergraduate students even during the COVID-19 pandemic would make the program more valuable. The lessons learnt will be applied to future training cohorts to optimize program impact and may be useful for similar programs in other settings.

ClinicalTrials.Gov: Pitfalls for pregnant women looking to enroll in studies.

The common exclusion of pregnant women from clinical HIV research warrants inquiry into those few studies that do include pregnant women. This commentary highlights some of the pitfalls of the ClinicalTrials.gov platform for its intended users--study participants, particularly pregnant women--and investigators looking to use its data for study. Some of the pitfalls include missing information; lack of historical reporting enforcement; difficulty searching for studies focused on pregnant women versus the fetus; inability to consistently find studies targeted at specific stages of pregnancy; and lack of information relating to whether a study intervention is investigational or previously approved by the FDA.

Makerere's contribution to the development of a high impact HIV research population-based cohort in the Rakai Region, Uganda.

Longitudinal population-based cohort studies can provide critical insights on temporal, spatial and sociodemographic changes in health status and health determinants that are not obtained by other study designs. However, establishing and maintaining such a cohort study can be challenging and expensive. Here, we describe the role of Makerere University in the development and conduct of such a cohort. We chronicle the first academia-led reports of HIV in East Africa; how this led to initiation of the Rakai Community Cohort Study in 1988, the first and oldest HIV cohort in sub-Saharan Africa; its impact on HIV prevention, care and treatment; how the cohort has been maintained; and opportunities, challenges, and future directions including non-communicable diseases.

Experiences and practices of key research team members in obtaining informed consent for pharmacogenetic research among people living with HIV: a qualitative study.

This study aimed to explore experiences and practices of key research team members in obtaining informed consent for pharmacogenetics research and to identify the approaches used for enhancing understanding during the consenting process. Data collection involved 15 qualitative, in-depth interviews with key researchers who were involved in obtaining informed consent from HIV infected individuals in Uganda for participation in pharmacogenetic clinical trials. The study explored two prominent themes: approaches used to convey information and enhance research participants' understanding and challenges faced during the consenting process. Several barriers and facilitators for obtaining consent were identified. Innovative and potentially effective consenting strategies were identified in this study that should be studied and independently verified.

Perceptions of HIV Research Participation Among Gay, Bisexual, and Other Men who Have Sex with Men and Transgender and Nonbinary Adults: Results From a Midwest Pride Event.

Human immunodeficiency virus (HIV) continues to disproportionately affect gay, bisexual, and other men who have sex with men (GBM) and transgender and nonbinary (trans/NB) individuals. This study investigated attitudes toward participation in HIV survey research, guided by Emanuel's framework for ethical clinical research (e.g., risk-benefit ratio, fair participant selection, respect for participants, social value, and collaborative partnership). GBM (n = 294) and trans/NB (n = 86) persons recruited at a Pride event in Milwaukee completed a survey assessing risks and benefits of participation in, and comfort responding to, sexual health surveys. Participants reported few ethical concerns (e.g., privacy and confidentiality), with notable differences by race, sexual orientation and gender identity, and prior research experiences. Implications for HIV research with GBM and trans/NB individuals are discussed.

Altruism: Scoping review of the literature and future directions for HIV cure-related research.

INTRODUCTION: The question of what motivates people to participate in research is particularly salient in the HIV field. While participation in HIV research was driven by survival in the 1980's and early 1990's, access to novel therapies became the primary motivator with the advent of combination antiretroviral therapy (cART) in the late 1990s. In the HIV cure-related research context, the concept of altruism has remained insufficiently studied. METHODS: We conducted a scoping review to better contextualize and understand how altruism is or could be operationalized in HIV cure-related research. We drew from the fields of altruism in general, clinical research, cancer, and HIV clinical research-including the HIV prevention, treatment, and cure-related research fields. DISCUSSION: Altruism as a key motivating factor for participation in clinical research has often been intertwined with the desire for personal benefit. The cancer field informs us that reasons for participation usually are multi-faceted and complex. The HIV prevention field offers ways to organize altruism-either by the types of benefits achieved (e.g., societal versus personal), or the origin of the values that motivate research participation. The HIV treatment literature reveals the critical role of clinical interactions in fostering altruism. There remains a dearth of in-depth knowledge regarding reasons surrounding research participation and the types of altruism displayed in HIV cure-related clinical research. CONCLUSION: Lessons learned from various research fields can guide questions which will inform the assessment of altruism in future HIV cure-related research.

AIDS Clinical Research in Spain-Large HIV Population, Geniality of Doctors, and Missing Opportunities.

The first cases of AIDS in Spain were reported in 1982. Since then over 85,000 persons with AIDS have been cumulated, with 60,000 deaths. Current estimates for people living with HIV are of 145,000, of whom 20% are unaware of it. This explains the still high rate of late HIV presenters. Although the HIV epidemic in Spain was originally driven mostly by injection drug users, since the year 2000 men having sex with men (MSM) account for most new incident HIV cases. Currently, MSM represent over 80% of new yearly HIV diagnoses. In the 80s, a subset of young doctors and nurses working at Internal Medicine hospital wards became deeply engaged in attending HIV-infected persons. Before the introduction of antiretrovirals in the earlier 1990s, diagnosis and treatment of opportunistic infections was their major task. A new wave of infectious diseases specialists was born. Following the wide introduction of triple combination therapy in the late 1990s, drug side effects and antiretroviral resistance led to built a core of highly devoted HIV specialists across the country. Since then, HIV medicine has improved and currently is largely conducted by multidisciplinary teams of health care providers working at hospital-based outclinics, where HIV-positive persons are generally seen every six months. Antiretroviral therapy is currently prescribed to roughly 75,000 persons, almost all attended at clinics belonging to the government health public system. Overall, the impact of HIV/AIDS publications by Spanish teams is the third most important in Europe. HIV research in Spain has classically been funded mostly by national and European public agencies along with pharma companies. Chronologically, some of the major contributions of Spanish HIV research are being in the field of tuberculosis, toxoplasmosis, leishmaniasis, HIV variants including HIV-2, drug resistance, pharmacology, antiretroviral drug-related toxicities, coinfection with viral hepatitis, design and participation in clinical trials with antiretrovirals, immunopathogenesis, ageing, and vaccine development.

The Need to Track Payment Incentives to Participate in HIV Research.

Providing incentives is an accepted and common practice in human subjects research, including clinical HIV research. While we know that financial incentives among similar studies can greatly vary, surprisingly little research exists on how to determine when such incentives are excessive or constitute an "undue inducement." Multiple factors, such as risks and benefits, study procedures, study budget, historical precedent, recommendations from institutional review boards, advice from other investigators, and local regulations may influence decisions about appropriate incentives, but little empirical data exist about what incentives are offered to potential research participants. Rules for acceptable gifts, services, and compensation should consider study location and population, but without a clearer understanding of currently offered incentives and how these practices match up to ethical beliefs of appropriateness, we continue to follow perceived trends without critical assessment. Here, we present one potential approach to explore the impact of financial incentives on biomedical HIV research and to further clarify undue inducement: the development of a framework to support ethical decision-making about payment to participate. This framework is based on input from people living with HIV, biomedical HIV researchers, ethicists, former study participants, and IRB members and includes a database that allows for tracking payment practices.

Voluntariness of consent to HIV clinical research: A conceptual and empirical pilot study.

Obtaining voluntary informed consent for research participation is an ethical imperative, yet there appears to be little consensus regarding what constitutes a voluntary consent decision. An instrument to assess influences on participants' consent decision and perceived voluntariness was developed and piloted in two South African HIV clinical trials. The pilot study found high levels of perceived voluntariness. The feeling of having no choice but to participate was significantly associated with lower perceived voluntariness. Overall the data suggest that it is possible to obtain voluntary and valid consent for research participants in ethically complex HIV clinical trials in a developing country context.

Equity issues were not fully addressed in Cochrane human immunodeficiency virus systematic reviews.

OBJECTIVE: To describe and summarize equity reporting in human immunodeficiency virus (HIV) systematic reviews and explore the extent to which equity issues are addressed and reported in HIV reviews using the PROGRESS Plus framework. STUDY DESIGN AND SETTING: Application of the PROGRESS Plus framework to a bibliometric analysis of HIV reviews in the Cochrane Database of Systematic Reviews. RESULTS: The analysis included 103 reviews published as of March 2014, with a median of five studies per review (first quartile; Q1 = 2; third quartile; Q3 = 11). Reporting of PROGRESS Plus factors was as follows: Place of residence (low, middle, and high income; 55.3%), place of residence (urban or rural; 24.3%), race or ethnicity (20.4%), occupation (10.7%), gender (65.0%), religion (1.9%), education (7.8%), socioeconomic position (10.7%), social networks and capital (1.0%), age (1.9%), and sexual orientation (3.8%). CONCLUSION: Gaps in the reporting of relevant equity indicators were identified within Cochrane HIV systematic review indicating that research is not consistently conducted through an equity lens. There is a need to incorporate PROGRESS Plus factors into both primary and secondary studies.

A humanized mouse model for HIV-2 infection and efficacy testing of a single-pill triple-drug combination anti-retroviral therapy.

While HIV-2 is a causative agent for AIDS in addition to the better studied HIV-1, there is currently no suitable animal model for experimental studies for HIV-2 infection and evaluating promising drugs in vivo. Here we evaluated humanized mice for their susceptibility to HIV-2 infection and tested a single-pill three drug formulation of anti-retrovirals (NRTIs abacavir and lamivudine, integrase inhibitor dolutegravir) (trade name, TriumeqR). Our results showed that hu-mice are susceptible to HIV-2 infection showing persistent viremia and CD4 T cell loss, key hallmarks of AIDS pathogenesis. Oral drug treatment led to full viral suppression and protection from CD4 T cell depletion. Cessation of therapy resulted in viral rebound and CD4 T cell loss. These proof-of-concept studies establish the utility of hu-mice for evaluating HIV-2 pathogenesis in more detail in the future, testing novel therapies and providing pre-clinical efficacy data of a three drug combination to treat HIV-2 infections.