Ethical guidelines and recommendations for human subjects research typically focus on protecting the individuals who directly participate in that research. However, additional people, including sex partners of research participants, can also face harms and burdens from medical studies. In human immunodeficiency virus (HIV) cure-related research, a persistent ethical and practical challenge surrounds the use of analytical antiretroviral treatment interruptions. The challenge is usually discussed in relation to risks to study participants, but serious dangers accrue to nonparticipants, including sex partners of study participants. This multidisciplinary supplement relays the risks for nonparticipating sex partners in HIV cure-related studies and addresses the ethical dilemmas raised by these studies, with recommendations for researchers, advocates, sponsors, and oversight bodies.

Purpose of review

Several promising experimental pathways exist for long-term control of HIV in the absence of antiretroviral therapy (HIV 'remission') and are now being tested in early clinical studies. These studies can be invasive and pose a host of distinctive risks to participants, as well as to nonparticipants, especially to participants' fetuses, and sexual partners.

Recent findings

Ethical analyses of these studies have mainly focused on the risks to study participants. They recommend, and some investigators implement, procedures to mitigate risks for participants or to offset them with direct, indirect, and nonmedical benefits. They also suggest ways to keep participants' consent highly voluntary and informed. Rarely do ethicists propose keeping the social value of studies high. Of these recommended responses, only the latter, rarer proposals help address the risk to nonparticipants, as would some novel ways to address that risk.

Summary

HIV remission studies pose a number of ethical dilemmas. Many current investigative approaches put the participant at significant risk, but well established guidelines exist for mitigating this risk. Ethical issues that are not being fully addressed include risk to nonparticipants and the need to consider the societal value of studies, for example, their prospective impact on the global HIV burden. VIDEO ABSTRACT.

A vaccine for COVID-19 is urgently needed. Several vaccine trial designs may significantly accelerate vaccine testing and approval, but also increase risks to human subjects. Concerns about whether the public would see such designs as ethical represent an important roadblock to their implementation; accordingly, both the World Health Organization and numerous scholars have called for consulting the public regarding them. We answered these calls by conducting a cross-national survey (n = 5920) in Australia, Canada, Hong Kong, New Zealand, South Africa, Singapore, the United Kingdom, and the United States. The survey explained key differences between traditional vaccine trials and two accelerated designs: a challenge trial or a trial integrating a Phase II safety and immunogenicity trial into a larger Phase III efficacy trial. Respondents' answers to comprehension questions indicate that they largely understood the key differences and ethical trade-offs between the designs from our descriptions. We asked respondents whether they would prefer scientists to conduct traditional trials or one of these two accelerated designs. We found broad majorities prefer for scientists to conduct challenge trials (75%) and integrated trials (63%) over standard trials. Even as respondents acknowledged the risks, they perceived both accelerated trials as similarly ethical to standard trial designs. This high support is consistent across every geography and demographic subgroup we examined, including vulnerable populations. These findings may help assuage some of the concerns surrounding accelerated designs.

Many people living with HIV (PLWHIV) state that they would be willing to take significant risks to be "cured" of the virus. However, how they interpret the word "cure" in this context is not clear. We used a randomized survey to examine whether PLWHIV had a different willingness to take a hypothetical HIV medication if it causes flu-like symptoms, but provides: (a) cure, (b) remission that was labeled "cure", or (c) remission. PLWHIV (n = 454) were more willing to take a medication that provided a "cure" versus a "remission" if the side effects lasted less than 1 year. PLWHIV were more willing to take a medication that provided a remission that was labeled "cure" versus a "remission" (p = 0.01) if the side effects lasted 2 weeks. Clinicians and researchers should be aware of the impact of the word "cure" and ensure that PLWHIV fully understand the possible outcomes of their treatment options.

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.