"I Know That I Was a Part of Making a Difference": Participant Motivations for Joining a Cure-Directed HIV Trial with an Analytical Treatment Interruption.

Analytical treatment interruption (ATI), defined as a closely monitored clinical pause in antiretroviral therapy (ART), is a core component of many HIV cure-directed clinical studies. ATIs may cause significant physical and psychosocial risks for people living with HIV and, as a result, integrating participant and community perspectives into clinical trial designs that include an ATI is crucial to ensuring a successful and person-centered trial. We conducted semi-structured interviews with participants enrolling in the BEAT-2 cure-directed trial (NCT03588715). Interviews elicited participant motivations and decision-making processes for trial participation along with participants' perceptions of the ATI. Interviews were recorded, transcribed, and analyzed using a directed content analysis. Fourteen of 15 trial participants completed interviews. The majority were Black (79%) cisgender male (79%). Participants noted several significant motivating factors contributing to their desire to enroll in the HIV cure-directed clinical trial, the most prominent being a desire to find a cure for HIV and help others in the HIV community. HIV care teams were the most commonly identified resource for patients when making the decision to enroll in the trial, and family, friends, and romantic partners also played a significant role. Altruism was a primary motivation for participation, although participants also shared interest in learning about HIV science and research. Participants had a strong understanding of trial procedures and displayed significant trust in the study team to keep them informed and healthy during their participation. The ATI was a significant source of anxiety for participants. Their primary worry was that their prior antiretroviral therapy (ART) regimen would no longer be effective once they resumed ART. Despite these concerns, participants shared considerable excitement for continued participation in the trial and being a part of the search toward an HIV cure.

Utilization of Antireflux Mucosectomy and Resection and Plication: A Novel Approach for the Management of Recurrent Gastroesophageal Reflux Disease after Prior Nissen Fundoplication or Transoral Incisionless Fundoplication.

Background: Nissen Fundoplication (NF) and Transoral Incisionless Fundoplication (TIF) are established procedures for the treatment of gastroesophageal reflux disease (GERD). However, the surgically induced plication can loosen over time. This multicenter study aims to evaluate the safety and efficacy of Antireflux Mucosectomy (ARMS) and Resection and Plication (RAP) in symptomatic patients with prior NF or TIF that has become loose. Patients and methods: Eighteen patients were enrolled in the study. Ten had prior TIF, while eight had prior NF. Half of these patients had a Hill Grade 3 Valve while the other half had a Hill Grade 2 valve. Endoscopic submucosal dissection (ESD) was performed in six patients, while endoscopic mucosal resection (EMR) was performed in twelve patients. A follow-up endoscopy was performed at 4-12 weeks. Results: At follow-up, 11 patients had a Hill Grade 1 valve, and seven patients had a Hill Grade 2 valve. All patients had improvement in symptoms for up to 32 months. Conclusions: In this pilot study, ARMS/RAP appears to be an effective option in patients who had prior NF or TIF with recurrent GERD symptoms.

Participant experiences using novel home-based blood collection device for viral load testing in HIV cure trials with analytical treatment interruptions

Background: HIV cure-directed clinical trials using analytical treatment interruptions (ATIs) require participants to adhere to frequent monitoring visits for viral load tests. Novel viral load monitoring strategies are needed to decrease participant burden during ATIs.Objective: To examine acceptability of a novel home-based blood collection device for viral load testing in the context of two ongoing ATI trials in Philadelphia, PA, United States.Methods: From January 2021 to February 2022, participants completed three in-depth interviews via teleconference during their participation in an ATI: (1) within two weeks of enrollment in the device study, (2) approximately four weeks after beginning to use the device, and (3) within two weeks of the end of the ATI when ART was re-initiated. We used conventional content analysis to analyze the data.Results: We recruited 17 participants: 15 were cisgender males, 1 cisgender female, and 1 transgender woman. We observed an overall 87% success rate in drawing blood with the device from home collection and found overall high acceptance of the device. A mean of 91.5 devices per participant were used for home-based blood collection. Most PWH viewed the device as relatively convenient, painless, easy to use, and a simple solution to frequent blood draws. The main challenge encountered was the inability to completely fill up devices with blood in some cases. Most participants reported positive experiences with mailing blood samples and could see themselves using the device on a regular basis outside of ATIs.Conclusions: Our study showed participant valued the novel home-based peripheral blood collection for viral load testing in the context of ATI trials. More research will be necessary to optimize implementation of the device and to assess whether blood collected can reliably measure viral loads in the context of ATI trials.

"We are looking at the future right now": community acceptability of a home-based viral load test device in the context of HIV cure-related research with analytical treatment interruptions in the United States.

BACKGROUND: People with HIV (PWH) and community members have advocated for the development of a home-based viral load test device that could make analytical treatment interruptions (ATIs) less burdensome. OBJECTIVE: We assessed community acceptability of a novel home-based viral load test device. METHODS: In 2021, we conducted 15 interviews and 3 virtual focus groups with PWH involved in HIV cure research. We used conventional thematic analysis to analyze the data. RESULTS: PWH viewed the home-based viral load test device as a critical adjunct in ongoing HIV cure trials with ATIs. The ability to test for viral load at home on demand would alleviate anxiety around being off ART. Participants drew parallels with glucometers used for diabetes. A preference was expressed for the home-based test to clearly indicate whether one was detectable or undetectable for HIV to mitigate risk of HIV transmission to partners. Perceived advantages of the device included convenience, sense of control, and no puncturing of veins. Perceived concerns were possible physical marks, user errors and navigating the logistics of mailing samples to a laboratory and receiving test results. Participants expressed mixed effects on stigma, such as helping normalize HIV, but increased potential for inadvertent disclosure of HIV status or ATI participation. Increasing pluri-potency of the device beyond viral load testing (e.g., CD4+ count test) would increase its utility. Participants suggested pairing the device with telemedicine and mobile health technologies. CONCLUSIONS: If proven effective, the home-based viral load test device will become a critical adjunct in HIV cure research and HIV care.

Preliminary Acceptability of a Home-Based Peripheral Blood Collection Device for Viral Load Testing in the Context of Analytical Treatment Interruptions in HIV Cure Trials: Results from a Nationwide Survey in the United States.

Frequent viral load testing is necessary during analytical treatment interruptions (ATIs) in HIV cure-directed clinical trials, though such may be burdensome and inconvenient to trial participants. We implemented a national, cross-sectional survey in the United States to examine the acceptability of a novel home-based peripheral blood collection device for HIV viral load testing. Between June and August 2021, we distributed an online survey to people with HIV (PWH) and community members, biomedical HIV cure researchers and HIV care providers. We performed descriptive analyses to summarize the results. We received 73 survey responses, with 51 from community members, 12 from biomedical HIV cure researchers and 10 from HIV care providers. Of those, 51 (70%) were cisgender men and 50 (68%) reported living with HIV. Most (>80% overall) indicated that the device would be helpful during ATI trials and they would feel comfortable using it themselves or recommending it to their patients/participants. Of the 50 PWH, 42 (84%) indicated they would use the device if they were participating in an ATI trial and 27 (54%) also expressed a willingness to use the device outside of HIV cure studies. Increasing sensitivity of viral load tests and pluri-potency of the device (CD4 count, chemistries) would augment acceptability. Survey findings provide evidence that viral load home testing would be an important adjunct to ongoing HIV cure-directed trials involving ATIs. Survey findings may help inform successful implementation and uptake of the device in the context of personalized HIV care.

Ethics of HIV cure research: an unfinished agenda.

BACKGROUND: The pursuit of a cure for HIV is a high priority for researchers, funding agencies, governments and people living with HIV (PLWH). To date, over 250 biomedical studies worldwide are or have been related to discovering a safe, effective, and scalable HIV cure, most of which are early translational research and experimental medicine. As HIV cure research increases, it is critical to identify and address the ethical challenges posed by this research. METHODS: We conducted a scoping review of the growing HIV cure research ethics literature, focusing on articles published in English peer-reviewed journals from 2013 to 2021. We extracted and summarized key developments in the ethics of HIV cure research. Twelve community advocates actively engaged in HIV cure research provided input on this summary and suggested areas warranting further ethical inquiry and foresight via email exchange and video conferencing. DISCUSSION: Despite substantial scholarship related to the ethics of HIV cure research, additional attention should focus on emerging issues in six categories of ethical issues: (1) social value (ongoing and emerging biomedical research and scalability considerations); (2) scientific validity (study design issues, such as the use of analytical treatment interruptions and placebos); (3) fair selection of participants (equity and justice considerations); (4) favorable benefit/risk balance (early phase research, benefit-risk balance, risk perception, psychological risks, and pediatric research); (5) informed consent (attention to language, decision-making, informed consent processes and scientific uncertainty); and (6) respect for enrolled participants and community (perspectives of people living with HIV and affected communities and representation). CONCLUSION: HIV cure research ethics has an unfinished agenda. Scientific research and bioethics should work in tandem to advance ethical HIV cure research. Because the science of HIV cure research will continue to rapidly advance, ethical considerations of the major themes we identified will need to be revisited and refined over time.

Re-examining the HIV 'functional cure' oxymoron: Time for precise terminology?

For over a decade, the binary concepts of 'sterilizing' versus 'functional' cure have provided an organizing framework for the field of HIV cure-related research. In this article, we examine how the expression 'functional cure' is employed within the field, published literature, and community understanding of HIV cure research. In our synthesis of the different meanings attributed to 'functional cure' within contemporary biomedical discourse, we argue that employing the 'functional cure' terminology poses a series of problems. The expression itself is contradictory and inconsistently used across a wide array of HIV cure research initiatives. Further, the meaning and acceptability of 'functional cure' within communities of people living with and affected by HIV is highly variable. After drawing lessons from other fields, such as cancer and infectious hepatitis cure research, we summarize our considerations and propose alternative language that may more aptly describe the scientific objectives in question. We call for closer attention to language used to describe HIV cure-related research, and for continued, significant, and strategic engagement to ensure acceptable and more precise terminology.