Stuart Rennie

The process of HIV status disclosure to HIV-positive youth in Kinshasa, Democratic Republic of the Congo.

Abstract As access to HIV/AIDS treatment increases in sub-Saharan Africa, greater attention is being paid to HIV-infected youth. Little is known about how HIV-positive youth are informed of their HIV infection. As part of a larger formative study informing a treatment program in Kinshasa, Democratic Republic of the Congo, semi-structured interviews were conducted with 19 youth (10–21 years) who had previously been told their HIV status and 21 caregivers who had disclosed the youths HIV status to the youth. Questions explored youths and caregivers’ experiences of and immediate reactions to disclosure. Youths median age at disclosure was 15 years old, with a range of 10–18 years based on caregiver reports (n=21) and from 10–19 years based on youth reports (n=18). The most common reasons spontaneously given for disclosing were the childs adherence to their treatment regimen (5/16), the need of the child to protect her/himself or stay healthy (5/16), the childs increasing age (4/16) and so that the child would know why they are suffering (3/16). Most youth (16/19) were surprised to learn of their diagnosis; 50% (8/16) wondered about the infections origins. A large majority felt that it is better for them to know their HIV status (88%; 15/17). HIV care and treatment programs must be prepared to address the psychosocial needs of youth and their caregivers during the disclosure process.

Male circumcision and HIV prevention: ethical, medical and public health tradeoffs in low-income countries

Ethical challenges surrounding the implementation of male circumcision as an HIV prevention strategy Researchers have been exploring the possibility of a correlation between male circumcision and lowered risk of HIV infection almost since the beginning of the HIV/AIDS epidemic.1 Results from a randomised controlled trial in South Africa in 2005 indicate that male circumcision protects men against the acquisition of HIV through heterosexual intercourse,2 confirming the findings from 20 years of observational studies.3 Circumcised men in the South African trial were 60% (95% CI 32% to 76%) less likely to acquire HIV than their uncircumcised counterparts. A mathematical modelling study, based on the South African trial, estimates that the practice of male circumcision could avert two million new HIV infections and 300 000 HIV-related deaths over the next 10 years in sub-Saharan Africa.4 More recently, two randomised controlled trials in Kisumu, Kenya and Rakai, Uganda showed, respectively, 53% and 48% reductions in HIV acquisition among circumcised men than uncircumcised men in the trial.5 These results strongly suggest that male circumcision could play an important role in the struggle against the continued rise in new HIV infections. However, as observers noted at the 2006 XVI International AIDS Conference in Toronto, Canada, excitement about the potential epidemiological impact has overshadowed the debate over the difficult translation of research on male circumcision, into policy and practice.6 Similar calls for caution have been raised before and elsewhere.7,8 The topic of male circumcision carries an enormous amount of ethical baggage. Male infants, worldwide, are circumcised for various medical, social and/or religious reasons. Circumcision is a cultural act and a surgical procedure; medical reasons are not the only reasons to circumcise that people have found and continue to find as compelling. Benatar and Benatar9 have argued that—when …

Principlism, medical individualism, and health promotion in resource-poor countries: can autonomy-based bioethics promote social justice and population health?

Through its adoption of the biomedical model of disease which promotes medical individualism and its reliance on the individual-based anthropology, mainstream bioethics has predominantly focused on respect for autonomy in the clinical setting and respect for person in the research site, emphasizing self-determination and freedom of choice. However, the emphasis on the individual has often led to moral vacuum, exaggeration of human agency, and a thin (liberal?) conception of justice. Applied to resource-poor countries and communities within developed countries, autonomy-based bioethics fails to address the root causes of diseases and public health crises with which individuals or communities are confronted. A sociological explanation of disease causation is needed to broaden principles of biomedical ethics and provides a renewed understanding of disease, freedom, medical practice, patient-physician relationship, risk and benefit of research and treatment, research priorities, and health policy.

Social and Ethical Implications of HIV Cure Research

CITATION: Tucker, J. D. & Stuart, R. 2014. Social and ethical implications of HIV cure research. AIDS, 28(9): 1247–1250, doi: 10.1097/QAD.0000000000000210.

Viewing Research Participation as a Moral Obligation: In Whose Interests?

A moral paradigm shift has been proposed for participation in health-related research. Its not just a praiseworthy option, some say; its a social obligation. Recasting research participation in this way would have global ramifications, however. Who ultimately stands to gain the most from it, and who has the most to lose?

Demographic and health surveillance: longitudinal ethical considerations

Longitudinal data gathered from health surveillance, when combined with detailed demographic information, can provide invaluable insight into disease outcomes. Many such surveillance sites exist in the developing world, particularly in Asia and sub-Saharan Africa, and focus on diseases such as HIV/AIDS, cholera, malaria and tuberculosis. The indistinct positions of such surveillance systems, often inhabiting an area between research, treatment and population health monitoring, means that the necessity of and responsibility for ethical oversight is unclear. This regulatory vacuum is further compounded by a lack of attention to longitudinal surveillance systems in ethics literature. In this paper, we explore some key ethical questions that arise during demographic and health surveillance in relation to ethical principles of beneficence, respect for persons and justice: health-care provision, informed consent and study sustainability.

Conducting unlinked anonymous HIV surveillance in developing countries: ethical, epidemiological, and public health concerns.

Stuart Rennie and colleagues argue that while unlinked anonymous HIV testing is valuable and ethical, such surveillance can be conducted in ethically questionable ways in certain circumstances.

Words Matter: Discussing Research Towards an HIV Cure in Research and Clinical Contexts

While still aspirational, the concept of curing HIV infection is gathering momentum as basic science concepts move into clinical research studies. The International AIDS Society has led strong advocacy efforts, paving the way for “HIV cure” to transition from being a four-letter word to being a strategic research priority of all the main HIV funding agencies worldwide, including the United States National Institutes of Health. This research excitement will gradually return to the clinic when patients pose questions to their HIV clinicians about how to interpret the meaning of HIV cure research. But HIV clinical cure research today has only peripheral relevance to the clinical management of HIV-infected individuals and simply using the term “cure” with patients in the clinic may invite more questions than it answers. As language wields power and HIV cure research is still early, now is a key time to clarify the nomenclature in research and clinical contexts. We first examine the concept of “cure” and then review three conceptual frameworks (sterilizing/functional cure, sustained virological response (SVR), clinical remission) for explaining the meaning of possible HIV cure to HIV-infected patients. The SVR concept may be useful in clinical research settings, but the concept of clinical remission has greater explanatory power, especially outside of research settings. With essentially all diseases, the term “cure” implies that all evidence of the disease has been eliminated and the individual has no chance of a recurrence. Given this high burden of diagnostic evidence and the high expectations it reproduces, the term “cure” is rarely used in the clinic. Most common infections are treated (e.g., bacterial infections) or resolved (e.g., viral infections). Meanwhile, in cancer clinics, physicians hesitate to use the word “cure” at least until sufficient time has passed after treatment to ensure that recurrence is highly unlikely. The difficult judgment about recurrence is contingent on the passage of time and testing. Decades of clinical experience provide physicians with a framework for prognosticating about the likelihood of recurrence. This is especially important in the cancer field in which some cancers recur many years after all evidence of cancer has resolved. Testing provides further data in which to inform patients about the probability of recurrence. Yet our experience with possible HIV cures is new and tools to detect and measure latently infected cells must be improved. We need to carefully examine the uncertainties and nomenclature of possible HIV cures. First, the concepts of sterilizing and functional cures provide a scientific foundation and likely catalyze hope, but ultimately have marginal relevance or explanatory power in the context of HIV-infected individuals. The International AIDS Society’s (IAS) Scientific Working Group, “Towards an HIV Cure” proposed a technical differentiation between a sterilizing and functional cure.1 A sterilizing cure is the elimination of all cells that could ever produce infectious HIV, while a functional cure is a less clearly defined term. Some have explained the latter as “the generation of effective host immunity to HIV that would result in lifelong control of the virus in the absence of therapy, despite not achieving the complete eradication of HIV.”1 The concept of functional cure has also been said to promise a stable health prognosis, the assurance of not being able to infect others, and have children without fear of HIV transmission. While sterilizing and functional cure concepts have helped galvanize advocacy and generated new hope for a cure, accurately defining either of these categories has proved challenging. The detection of HIV DNA alongside the absence of replication-competent, infectious HIV in both the Berlin patient2 and the Mississippi baby3 illustrate that while these patients appear to represent a sterilizing cure, definitively proving the absence of infectious virus is challenging. Using the functional cure concept may undermine the vigilance necessary to follow these patients long-term in clinical settings. Few other diseases have functional cures4 and this further complicates explaining a functional cure to patients. Second, the SVR concept balances the science with appropriate clinical uncertainty, but would also be unfamiliar to many HIV-infected individuals. SVR refers to lack of detectable RNA in the serum of individuals with hepatitis C virus (HCV) at six months after stopping therapy.5 This definition directly corresponds to a measurable unit in the blood at a specific time point, appealing to scientists and many physicians. Although the SVR concept comes close to complete cure, there is still a subset of HCV-infected patients who achieve SVR but then display persistent hepatic inflammation and develop cirrhosis.6 The Forum for Collaborative HIV Research has proposed using the term “sustained virological suppression off therapy” (SVOT), analogous to the SVR concept. This term would likely be useful in early clinical research settings, but would have less utility as more individuals enter clinical research studies. Finally, the concept of clinical remission denotes improvement with some uncertainty and is already well-entrenched in medical settings. The term’s medical use stretches back to the 15th century and means, “lessening the severity of a disease or symptom for a period”.7 The concept is frequently used in the cancer clinic and describes the absence of disease activity in the setting of chronic cancer. Remission is used to describe scenarios in which cancer is curable (e.g., acute lymphoblastic leukemia), incurable (e.g., metastic melanoma), or unknown (e.g., carcinoma of unknown primary). Although widely used in cancer clinical discussions, clinical remission is also used to describe a wide range of other non-cancer chronic diseases. The remission concept clearly denotes improvement, but also underscores vigilance and uncertainty that require the need for careful follow-up. In addition, the remission concept can be further subdivided into partial and complete remissions, a helpful designation given the likely stepwise progression towards an HIV cure. Although the remission concept may be less familiar in low-income country settings, it would be largely recognizable to HIV-infected individuals in a wide range of other settings. The remission concept has been used by leadership at the National Institute for Health’s National Institute of Allergy and Infectious Diseases 8 and the International AIDS Society.9 The concept of “HIV remission” may be particularly useful as more HIV-infected individuals enter clinical trials and physicians are discussing this concept outside of research settings. Embracing the concept of clinical remission does not mean that we have abandoned hope of finding therapies that could create a sterilizing cure, nor are we advocating for scientific research and advocacy to halt the aspirational (towards an HIV cure) language that has ignited a new subfield of HIV research. Clinical discussions between physicians and patients require honesty about the uncertainty in this undertaking. Such careful communication may present waves of hope, misperception, and disappointment among HIV-infected individuals and the health professionals who serve them. Should effective HIV cures be developed, the downstream effects on health and well-being, risk of onward transmission, risk of re-acquisition, and social stigma are unclear. Furthermore, these larger biological and social questions will not be addressed by nomenclature. But nomenclature critically sets the bar for expectations as research advances and clinicians increasingly discuss cure research with their HIV patients. While only two individuals in all of history appear to be cured of HIV infection, the concept of remission is both easier to explain and more consistent with the state of the science. We owe it to our HIV patients to use caution and consider the conceptual framework of HIV remission.

Developing ethics guidance for HIV prevention research: the HIV Prevention Trials Network approach

More than 25 years into the HIV epidemic, in excess of 2 million new infections continue to occur each year. HIV prevention research is crucial for groups at heightened risk for HIV, but the design and conduct of HIV prevention research with vulnerable populations worldwide raises considerable ethical challenges. The HIV Prevention Trials Network (HPTN) is a global collaborative network that conducts clinical and behavioural studies on non-vaccine interventions to reduce the transmission of HIV. In 2003, the HPTN developed ethical guidance to enhance the responsible conduct of its research activities and as a distinctive contribution to global research ethics. In what follows, the developments that motivated the drafting of a revised ethics document in 2009 are described, including the process by which that revision took place and some of the key differences between the HPTN ethics guidance and other relevant guidelines in the field.

Evidence-based planning of a randomized controlled trial on diaphragm use for prevention of sexually transmitted infections

Objectives: We conducted formative research to evaluate the acceptability and feasibility of continuous diaphragm use among low-income women highly exposed to sexually transmitted infections (STIs) in Madagascar. Goal: To identify potential obstacles to researching the effectiveness of diaphragm use for STI prevention in a randomized controlled trial. Study Design: Mixed methods to collect complex information. In a quantitative pilot study, women were asked to use diaphragms continuously (removing once daily for cleaning) for 8 weeks and promote consistent male condom use; they were interviewed and examined clinically during follow-up. Focus group discussions (FGDs) were conducted pre-/postpilot study. Audiotaped FGDs were transcribed, translated, coded, and analyzed. Results: Ninety-three women participated in prepilot FGDs, 91 in the pilot study, and 82 in postpilot FGDs. Diaphragm use was acceptable and feasible, but participants reported lower condom use in FGDs than during interviews. Most participants reported in interviews that they used their diaphragms continuously, but FGDs revealed that extensive intravaginal hygiene practices may impede effective continuous diaphragm use. Despite counseling by study staff, FGDs revealed that participants believed the diaphragm provided effective protection against STIs and pregnancy. Conclusions: Mixed methods formative research generated information that the prospective pilot study alone could not provide and revealed contradictory findings. Results have methodological and ethical implications that affect trial design including provision of free hormonal contraceptives, and additional instructions for vaginal hygiene to avoid displacing the diaphragm. Mixed methods formative research should be encouraged to promote evidence-based study design and implementation.