A landscape analysis of HIV cure-related clinical research in 2019.

OBJECTIVES: In 2018, we surveyed investigators conducting HIV cure-related clinical research, drawing on information from the online listing established by Treatment Action Group (TAG). The purpose of the survey was to facilitate a landscape analysis of the field. In 2019, we fielded a second survey in order to provide updated information and assess any shifts in the landscape. METHODS: Trials and observational studies listed as of August 16, 2019 formed the sample set. Survey questions addressed funding, trial development, recruitment, enrollment, participant demographics, antiretroviral therapy status, HIV reservoir assays, invasive procedures, study completion, data sharing and dissemination plans. A survey was sent to the contact(s) for each study. Supplemental information was collected from clinicaltrials.gov and available presentations/publications of study results. RESULTS: A total of 97 interventional trials and 36 observational studies were identified, with 30 including analytical treatment interruptions. Total projected enrollment is 13,732 participants, with observational studies contributing the majority (8,325). Most interventional trials are in early phases. The majority of current research is located in the USA, involves predominately male participants and is limited in racial and ethnic diversity. Prespecified demographic enrollment targets are rare. Two thirds of respondents to our previous survey reported that enrollment is progressing more slowly than anticipated. CONCLUSIONS: A diverse range of interventions are being evaluated in HIV cure research, but participant diversity is far from optimal with a continuing underrepresentation of women. Broadening inclusion and geographic reach will be necessary to achieve the goal of developing widely effective, safe and accessible curative interventions.

A landscape analysis of HIV cure-related clinical trials and observational studies in 2018.

OBJECTIVES: The community-based organisation Treatment Action Group has established an online listing of HIV cure-related trials and observational studies derived from trial registries. Our objective was to use the listing as a basis for a landscape analysis of the current status of HIV cure-related clinical research. METHODS: Trials and observational studies listed as of August 2018 formed the sample set. Survey questions were developed on trial development, trial design, recruitment, enrolment, study completion and dissemination plans. A survey was sent to the contact(s) for each study. Supplemental information was collected from clinicaltrials.gov. The full dataset was then analysed. RESULTS: A total of 99 interventional trials and 29 observational studies were included. Diverse interventions are under evaluation, including combinations of experimental candidates. Current studies plan to enrol over 7000 participants. Projected completion dates for ~90% of the sample fell between the fourth quarter of 2018 and the end of 2020. Potential obstacles to enrolment that were reported included concerns over invasive procedures and lack of potential benefit to participants. Data on the sex and ethnicity of enrollees were limited but sufficient to note a significant under-representation of women. CONCLUSIONS: A considerable amount of HIV cure-related clinical research is under way. The results from these studies, which should help shape the future of the field, will become available over the next 2-4 years. Diversity both geographically and in terms of enrollees remains limited, particularly in terms of the participation of women, a concern that could significantly affect the generalisability of the findings.

Recommendations for analytical antiretroviral treatment interruptions in HIV research trials-report of a consensus meeting.

Analytical antiretroviral treatment interruption (ATI) is an important feature of HIV research, seeking to achieve sustained viral suppression in the absence of antiretroviral therapy (ART) when the goal is to measure effects of novel therapeutic interventions on time to viral load rebound or altered viral setpoint. Trials with ATIs also intend to determine host, virological, and immunological markers that are predictive of sustained viral control off ART. Although ATI is increasingly incorporated into proof-of-concept trials, no consensus has been reached on strategies to maximise its utility and minimise its risks. In addition, differences in ATI trial designs hinder the ability to compare efficacy and safety of interventions across trials. Therefore, we held a meeting of stakeholders from many interest groups, including scientists, clinicians, ethicists, social scientists, regulators, people living with HIV, and advocacy groups, to discuss the main challenges concerning ATI studies and to formulate recommendations with an emphasis on strategies for risk mitigation and monitoring, ART resumption criteria, and ethical considerations. In this Review, we present the major points of discussion and consensus views achieved with the goal of informing the conduct of ATIs to maximise the knowledge gained and minimise the risk to participants in clinical HIV research.

Rallying CROI.

The 24th Conference on Retroviruses and Opportunistic Infections, which took place from February 13-16, is the preeminent US-based scientific meeting on HIV research.

International AIDS Society global scientific strategy: towards an HIV cure 2016.

Antiretroviral therapy is not curative. Given the challenges in providing lifelong therapy to a global population of more than 35 million people living with HIV, there is intense interest in developing a cure for HIV infection. The International AIDS Society convened a group of international experts to develop a scientific strategy for research towards an HIV cure. This Perspective summarizes the group's strategy.