Homo adhaerens : Risk and adherence in biomedical HIV prevention research

Introduction

On May 10^th, 2012, the Antiviral Drugs Advisory Committee of the Food and Drug Administration (FDA) assembled in Washington DC to discuss approving Truvada as the first drug that could be taken to prevent HIV infection. Truvada, a combination of tenofovir disoproxil fumarate (TDF) and emtricitabine (FTC), is an antiretroviral drug already in use to treat patients living with HIV. It had recently been demonstrated to work as pre-exposure prophylaxis (PrEP) in several clinical trials. When taken daily, the pill offered some degree of immunity to HIV. In response to an application filed by Truvada’s patent holder, Gilead Sciences, the FDA was to decide if the drug should be approved for use by high-risk, HIV-negative consumers. After a twelve-hour meeting, the committee voted nineteen to three in favor of approval (Birnkrant, 2012).

However, the nearly unanimous vote belied significant contention among activists and public health officials. Members of the committee were concerned about the demographic groups included in the clinical trials, the significance of strict adherence, and the ability for clinical research to scale to population interventions. Lauren Wood, the committee’s health disparities specialist, noted that Truvada hadn’t been tested adequately on Black patients, who are most at risk to contract HIV in the United States and also most susceptible to kidney damage linked to AIDS drugs. She justified her vote, no for all designations, with the comment:

… there is no data [on PrEP] in any American women. The next higher population where we propose to be targeting our therapeutic interventions for, where the epidemic is exploding in this country, in rural areas, in urban areas, in the Mid-Atlantic and in the South, is in heterosexual black women. And I want to make the committee aware that there is not a single African American female in any one of the studies that has been put forward for approval. (Birnkrant, 2012)

She added that the adherence threshold that researchers established as necessary to fully prevent HIV, 90%, was not met in any of the trials. This concern about low adherence was echoed by Doris Strader, an Associate Professor of Medicine at the University of Vermont College of Medicine, who said:

… it’s hard for me to uncouple adherence from efficacy. If we don’t have sufficient adherence to a drug, it’s hard for me to know what to make of the data if 40 percent of people may or may not adhere to the drug as it was prescribed. So it was difficult for me to decide on the high-risk MSM population, and certainly on the FEM-PrEP [female] population, which I believe they said was stopped early because the adherence was so poor, they could not make any judgments about whether it was effective or not (Birnkrant, 2012).

But the large majority of the committee voted in favor of approval. Matt Sharp, a patient representative from San Francisco, voted yes on hopeful and impatient grounds, suggesting that even if some identity groups are understudied, Truvada would be an important new tool in the toolbox of prevention:

I also really think this provides an amazing opportunity for turning the tide of the epidemic in terms of getting people tested, reducing STI infections, all of the things that we need to move on. Just like Daniel said, we need to turn this dial. So that’s the reason I really felt strongly, even though, as you go down the list, some of the populations, the data’s not as strong. But to me, as somebody who’s been living with HIV for 23 years, I’m tired of seeing the ongoing infection rate. (Birnkrant, 2012)

These remarks acknowledge a clear concern with Truvada that is offset by the sense of urgency perpetually present in HIV public health discourse. As the committee members were undoubtedly aware, almost one million people in the United States and 36.7 million worldwide were living with HIV in 2012 (CDC, 2016a; WHO, 2005). The regulatory committee was caught in a double bind; immediately approving the drug was appealing because of its demonstrated potential as a prevention tool, but such promise could be easily undermined if the drug was not made accessible to those who are most vulnerable.

Since 2012, the inequalities that committee members anticipated have in many ways become a reality. Namely, the demographic groups with the highest risk of contracting HIV are receiving the fewest prescriptions for Truvada. At the 2016 ASM Microbe Conference, Gilead announced results of an electronic survey of pharmacies that dispense Truvada. They counted the number of people who had filled Truvada prescriptions at every commercial pharmacy in the country, along with each consumer’s race, ethnicity, and gender. The results of the survey indicated a rise in overall users: Over 80,000 unique patients had filled Truvada prescriptions. However, only 10% of those prescriptions were filled by African Americans and 11.7% by Hispanic and Latino Americans (Bush et al., 2016). Conversely, of the total new HIV diagnoses that year, African Americans made up 44%, Hispanic Americans 17%, and whites only 5.2% (CDC, 2016b). Later analysis of the same data also raised concerns about a lack of Truvada use in women. According to Sullivan and colleagues (2018), the PrEP-to-need ratio (the ratio of the number of PrEP users to the number of new HIV diagnoses) of men was over three times greater than that of women in 2017. While critics suspect that Gilead’s survey methods undercount total PrEP prescriptions, the data reaffirm the fear that Truvada is in the position to reinforce inequalities.

Addressing another concern for regulators, cohort studies that followed Truvada users after approval reported that participants’ willingness to initiate and adhere to the prescribed regimen for taking PrEP is mixed. In January 2017, a team of social science researchers operating a demonstration project through the Brazilian Public Health System reported high adherence among its participants: 94.1% of patients, both men who have sex with men (MSM) and transgender women, had blood levels of tenofovir in the protective range (Hoagland et al., 2017). In contrast, in a demonstration project of young men who have sex with men in Chicago, adherence started at 63.2%, but decreased to 20% by the last week of the study. Researchers indicated a strong need for attention to adherence counseling (Hosek et al., 2013).

Public health researchers reacted to these inequalities by illuminating barriers to PrEP access and adherence. Smith et al.’s (2016) national survey of healthcare providers illuminates physicians’ lack of awareness of PrEP options, and Bauermeister et al. (2013) articulate the cost barriers (real and perceived) that prevent members of target groups from accessing the drug. The overall tone of these studies is optimistic: Expert advice can be leveraged to tweak public health interventions, and new legislation can be passed to make Truvada an equitable intervention. Working in parallel with public health scholars, activists address the structural racism that creates health inequalities. Kenyon Farrow, a member of Treatment Action Group (an HIV/AIDS activist organization) writes, ‘we must make the pricing of various treatments – particularly PrEP, antiretroviral treatment, and Hepatitis C virus drugs – an issue of racial justice’ (Farrow, 2016). This perspective draws attention to the longstanding institutional racism that underlies proximal healthcare access inequalities.

However, scholars have yet to analyze critically the decade-long regime of knowledge production from which Truvada emerges, initially heralded as a miraculous end to the HIV epidemic. The FDA committee’s deliberation relies on understandings of adherence, efficacy, and universality that are produced, negotiated and constrained by clinical experimentation. Focusing on these clinical trials, I ask: Does clinical research design and execution contribute to PrEP access inequalities? And, what participants, patients, and subjects do epidemiological understandings of adherence to PrEP and risk for HIV privilege? I trace the process of knowledge production through which these understandings crystallize. I draw on Latour’s (1987) translational model, which articulates that claims must be recognized by a critical mass of actors before they can become facts. Applying this model to the drug development process, Sismondo (2015) demonstrates that networks of pharmaceutical representatives, physicians, academic researchers, ghostwriters and contract research organizations curate and transform pharmaceutical knowledge. To open the black box of pharmaceutical research, Sismondo recommends not to assess the truth value of information that circulates as fact, but rather to understand what he calls the ‘political economies of scientific knowledge’ through which this information is produced, distributed, and made useful (Sismondo, 2015: 305). Heeding Sismondo’s advice, I dissect PrEP clinical trials, revealing the unique social circumstances under which knowledge about PrEP is produced, how this knowledge circulates, and the larger social projects to which it is yoked.

To fully appreciate the complexity of PrEP discourse, my research was methodologically plural. The bulk of my analysis is based on a close reading of articles published in epidemiological and biomedical journals like The Journal of Acquired Immune Deficiency Syndromes, The New England Journal of Medicine, Current HIV Research, and The Lancet HIV. I relied on guides like Treatment Action Group’s ‘HIV Research in the Era of PrEP’ to familiarize myself with the landscape of secondary literature that has already been incredibly well mapped by other social scientists (Jefferys et al., 2017). My attention to these studies is mainly trained on their methodologies – specifically those of recruitment and protocol design. I also conducted a handful of interviews with key activists, advocates and organizers who were either on community advisory boards or otherwise involved in PrEP research.

Reflecting on these sources, I argue that in grappling with adherence and risk in order to demonstrate efficacy, the clinical research of biomedical HIV prevention reveals a subject of biopolitics, whom I name Homo adhaerens. This figure is the ideal candidate for pharmaceutical research: poised to adhere perfectly to an intervention but facing a high risk – in this case, a high risk of contracting HIV. Unlike the average body, understood to be medicine’s default research subject, Homo adhaerens is an ideal that no individual subject meets. In the context of PrEP trials, Homo adhaerens is disciplined to maintain bodily immunity in order to maximize the health of the population. The construct also has implications beyond research: I find that when PrEP research is applied to public health interventions, and marketed as Truvada, Homo adhaerens’ idyllic position as a subject of biomedicine becomes the standard to which PrEP users are held. To be prescribed Truvada, patients must have access to a well-informed physician, the financial capital to purchase the drug, and the social positioning to adhere to a daily pharmaceutical regimen. Appealing to Homo adhaerens allows stakeholders to compartmentalize social concerns by applying a biomedical rationale to an inherently social epidemic.

While I examine Homo adhaerens strictly in the context of PrEP research, adherence has been a primary concern of social scientists and medical researchers for half a century. The biopolitical figure of Homo adhaerens began to take shape before PrEP research, and even before the emergence of HIV: As early as 1950, physicians were acutely aware that the growth of chronic illness and the coincident invention of less-toxic pharmaceuticals (that could be used indefinitely for both therapy and prophylaxis) would demand that patients commit to indefinite treatment plans. These protracted therapeutic regimens posed a problem for clinical researchers, who were forced to rely on patients’ unreliable self-reports of protocol compliance. In response, understanding and circumventing this human error became a prominent area of academic inquiry. In 1969, one team of public health researchers devised an observational study to determine the prevalence of subject noncompliance in research. They compared the urine of children prescribed daily penicillin to prevent hay fever with their mothers’ reports of the same day. The researchers note that while 88% of mothers reported that their child had taken the day’s dose of penicillin in an interview, only 68% of the children’s urine tests revealed levels of penicillin adequate to confirm their response (Gordis et al., 1969). Not only were the families noncompliant, they served as unreliable co-investigators.

Acknowledging the problem of adherence, epidemiologists categorized methodological approaches into two broad groups: explanatory research, which isolates the proximal efficacy of a drug by excluding participants who become ineligible or are noncompliant, and pragmatic research, which considers the intervention as it is applied in practice. The pragmatic approach takes the form of intention-to-treat (ITT) analysis, which compares the treatment group (including all randomly assigned participants regardless of deviation from the protocol), with the control group (Tsiatis, 1990). This method of analysis became a widespread RCT template. In fact, most of the clinical studies I analyze began with intention-to-treat protocols, but because adherence proved to be so low and HIV seroconversion so rare, were modified to produce more useful results.

While my research focuses on phase-III and IV clinical trials, Homo adhaerens also emerges at other sites of knowledge production. For example, smaller studies of drug safety, as Fisher (2020) recounts, often attract healthy participants with cash incentives. Subjects – for whom participation in the trial is often a primary source of income – are often housed on-site for the duration of the trial to ensure adherence, and are selected for their good health and lack of ‘risk factors’. Both in Fisher’s case and my own, researchers are concerned with adherence, validity, and risk, albeit for different reasons. Because of this, Homo adhaerens, as I will elaborate further, provides a generative way of thinking about the weight of adherence and its relationship to risk across epistemic spaces.

Of course, concerns about adherence also exist beyond clinical trials, and as such Homo adhaerens is cast in similar roles across different theaters. Sismondo notes that pharmaceutical companies frame non-adherence as a failure in customer retention and, as a result, invest heavily in programs designed to encourage patients to refill their prescriptions. Sismondo’s industry informants disagree on what behavioral model and corresponding intervention best describe and remedy non-adherence. Some ‘adherence specialists’ believe that patients are rational and reasoning consumers who can be taught the benefits of adherence through communication-oriented interventions. Others opt to coax behavioral changes by modifying packaging to nudge patients to stick to their schedule (Sismondo, 2018). Like the RCT, these technological interventions to improve compliance have existed since the mid-20^th century, and are cemented in patents like Walter Aven’s 1963 ‘Calendar Reminder and [Pill] Dispensing Device’, for a paper calendar with date boxes that could be torn away to reveal pills, serving both to remind a patient of his or her daily pharmaceutical ritual, and to leave a record of adherence (Aven, 1963).

Indeed, adherence to HIV treatment has its own fraught history. Researchers and policymakers at the turn of the millennium were concerned that patients in the Global South would not reap the benefits of life-sustaining antivirals (which in their earliest iterations required the timed consumption of multiple doses per day) – or even worse, contribute to the growth of resistant strains – due to their alleged inadequate compliance (Harries et al., 2001). This perception continues today; Crane’s (2013) ethnography of HIV therapy in Uganda reveals that concerns about adherence (which are often overblown) shift the burden of disease onto the individual, rather than to social determinants of health like economic wellbeing, housing and safety. In her words, poor-faith concern for adherence dismisses sick patients as ‘“noncompliant” or “poorly adherent” rather than socially and economically marginalized’ (Crane, 2013: 32).

This historical context will prove helpful as I begin to sift through PrEP discourse to understand how Homo adhaerens emerges in this narrow context. Moments when adherence comes into focus, like those described above, when pieced together, could create a genealogy of Homo adhaerens. In this case study, I focus on the way that epidemiological language, methods and organizing ideas in biomedical HIV prevention frame adherence. What shape does Homo adhaerens take in PrEP research?

I also discuss how understandings of adherence are co-produced, contested and reframed by activist and advocacy campaigns. Revisiting Epstein’s (1996) argument that activists leverage a unique moral and scientific expertise to negotiate with pharmaceutical companies and scientific authorities, I turn my attention to activist involvement with the ongoing DISCOVER PrEP trial. Listening carefully to activist concerns, I demonstrate that activists either aspire for Homo adhaerens as a standard, making the liberal argument that expanding access could make PrEP successful. Or, they leverage a radical critique of the epistemology through which Homo adhaerens emerges, suggesting that research subjects and patients are situated in a corporate epistemology whereby Gilead expands their franchise of intellectual property to generate value for shareholders. In articulating their claims, activists continue to call on the strategies that Epstein (1996) delineates; they challenge the impure science of PrEP epidemiology, the greed of pharmaceutical companies, and the lack of broader attention to HIV prevention efforts.

Homo adhaerens in biomedical HIV prevention research

Just after the turn of the millennium, biomedical HIV prevention research exploded. Clinical researchers from universities throughout the United States and other wealthy countries organized large randomized controlled trials (RCTs) of PrEP to take place throughout the Global South. They sought funding from the National Institutes of Health and global health giants like the Bill and Melinda Gates Foundation and Family Health International. In this section, I analyze three PrEP clinical trials, paying close attention to the novel strategies that researchers used to study biomedical prevention.

The contention surrounding these strategies was brought to the foreground in 2004, when Principal Investigator Kimberly Page-Shafer from the University of California, San Francisco (UCSF) planned to test tenofovir for HIV prevention. She worked with the Cambodian Ministry of Health, the U.S. National Institute of Allergy and Infectious Diseases (NIAID) and the Bill and Melinda Gates Foundation to recruit around 1,000 sex workers in Cambodia to participate in a two-armed clinical trial. One arm would receive a placebo and the other tenofovir. Both would be blinded to their assignment, and would also receive condoms and rigorous risk-reduction education (Cohen, 2004).

Despite the vulnerable target population, according to international mandates the trial was ethical. Article 29 of the Declaration of Helsinki requires a new intervention ‘be tested against those of the best current prophylactic … methods. This does not exclude the use of placebo, or no treatment, in studies where no proven prophylactic … method exists’ (World Medical Association, 2013: 2193). In this case, an educational intervention and the distribution of condoms was considered to be the standard of care in biomedical HIV prevention, meeting equipoise requirements.

However, controversy surrounding PrEP trials had been stirring since earlier that year, focusing on issues that exceeded the scope of the Declaration of Helsinki. ACT UP Paris, an AIDS activist organization that can be traced to the 1980s in New York, had been monitoring PrEP clinical trials. At the XV International AIDS Conference in Bangkok, Thailand, ACT UP demonstrated at Gilead’s booth holding signs that said, ‘Gilead Prefers us HIV+’ and ‘Gilead has blood on its hands’. In a press release that accompanied the demonstration, the activists alleged that Gilead had provided inadequate prevention counseling in the placebo arm, was not offering to provide ARVs and medical care for participants who seroconverted or experienced serious side effects during the trial, and that the community of sex workers Gilead targeted had not been involved in designing the study (ACT UP Paris, 2005). In what some have speculated was a response to this unrest, the Cambodian Ministry of Health notified collaborators, with little notice or explanation, that, on the orders of Prime Minister Hun Se and just a few days after it began, the trial must be halted. Investigators were shocked, protesting that they had worked closely with regulatory bodies in Cambodia and the United States.

The biopolitics of PrEP

How does Homo adhaerens emerge through these two epidemiological strategies? While discourses that produce Homo adhaerens are usually limited to addressing adherence – as is the case in the brief history I outlined in the introduction – in this case, adherence is uniquely tied to, and understood in terms of, risk for HIV. In these three clinical trials – Page-Schaffer’s cancelled study of Cambodian sex workers, Grant’s study of men and transgender women who have sex with men, and Baeten’s study of serodiscordant partners – subjects are made legible only if they are both members of a social group deemed high-risk and perfectly adherent to PrEP. By instating this funnel through which participants must pass, researchers isolate an ideal research subject who is disciplined enough to maintain the hygiene of his individual body, but also exposed enough to HIV to demonstrate PrEP’s efficacy. Of course, adherence and risk aren’t mutually exclusive, but biomedical HIV prevention research constructs understandings of both that are overdetermined and difficult to reconcile.

In The History of Sexuality, and his later lectures at the College De France, Foucault traces a genealogy of power in Europe. Since feudalism, the sovereign power of the king functioned to ‘let live or make die’, and was symbolized by the wielding of a sword. In the 16^th century, states established a handful of disciplinary institutions – prisons, asylums, hospitals, and schools – to cultivate individual bodies in adherence with strict norms. Later, in 17^th-century Europe, Foucault identifies a diffuse and amorphous biopower that seeks to ‘make live and let die’. Biopower comprises a collection of ‘numerous and diverse techniques for achieving the subjugation of bodies and the control of populations’ (Foucault, 1990: 140). These techniques, which Foucault calls dispositifs, operate on two poles: the anatomo-politics of the human body, and the biopolitics of the population. Anatomo-politics encourages the self-maintenance of an individual’s body, while biopolitics manages the population – monitoring it with measures that include fertility rates, mortality rates and metrics of productive capacity. Both introduce incitement, the ability to exercise power by promoting life, to the deductive power of the sovereign state (Foucault, 1990, 2007). Homo adhaerens straddles these poles, emerging from public health discourse that addresses the body in terms of the population.

First, Homo adhaerens is used as an ideal research subject who can be transposed across trial sites to represent the population of PrEP users at large. As I detailed above, Grant and Baeten use sub-group analysis to sequester a sample of perfectly adherent participants that can provide clean knowledge about efficacy. Following their methodology, epidemiologists across the world are able to compare PrEP’s efficacy across similar subjects. This project, a niche example of the RCT’s basic epistemology, elides the social context of noncompliance to facilitate researchers’ dismissal of site-specific social concerns. Homo adhaerens becomes the privileged biological citizen and research subject because of their self-disciplining ability.

Second, Homo adhaerens manifests itself as an expectation of adherence that incites patients to play an active role in managing their own risk. Rose and Rabinow argue that biopolitics in the 21^st century has mutated towards a focus on the molecular, giving rise to biopolitical strategies that promote self-enhancement and personal autonomy. This atomizing approach gives rise to ‘the birth of new modes of individualization and conceptions of autonomy’ (Rabinow and Rose, 2006: 204) like Homo adhaerens. Accordingly, as clinical research takes the form of demonstration projects, Homo adhaerens is tied to the logics of the United States’ market-based healthcare system. Subjects are expected to have financial security, transportation and access to medical services, and those who do not meet these criteria are further excluded from knowledge production. This standard, along with the public health campaigns, surveillance recommendations and technological adherence-monitoring platforms that enforce it, suffers from myopia. Adherence is a crucial pitfall of many prophylactic interventions: One landmark study of oral birth control users, for example, found that only 42% of them took the pill every day (Oakley et al., 1991). Confronting the same concern as PrEP researchers, Oakley et al. suggested that ‘we need to redesign clinical interventions to … help more women be prepared to solve problems [with adherence] when they arise’ (1991: 154).

The analytic figure of Homo adhaerens addresses this rift between the ideal research subject and actual patient. The name reflects the imperfection of transforming the ideal research subject into the ideal recipient of a public health intervention. Just as Homo economicus maximizes utility by fashioning the body as a productive machine, Homo adhaerens minimizes the risk of contracting HIV by committing to a daily ritual of immunity. And like Homo economicus, who is untouched by inherent human irrationality, Homo adhaerens is not a behavioral reality (Arendt, 2013). As I flesh out below, Homo adhaerens emerges as an expectation to which patients are held, a lens through which individual subjectivities are refracted, and a fantasy that activists herald as a possibility for all patients. While I use biomedical HIV prevention research as a case study, Homo adhaerens has the capacity to serve as an analytic intervention wherever adherence, risk, and structural inequality serve as a barrier to the RCT’s ideals of validity and efficacy.

Remaking Homo adhaerens in the United States

Truvada for PrEP was approved by the FDA in 2012. In its conditional approval notice for Truvada, the FDA instated several post-marketing requirements. These projects aimed to elicit a better understanding of side effects in pregnant women and the general population, assess the risk of the development of resistant HIV strains, determine the dose-response relationship between adherence and immunity, and validate a behavioral questionnaire that could be used in later trials (Food and Drug Administration, 2012). In addition to these FDA mandated trials, several third parties – insurance companies, hospitals and NGOs – sponsored cohort studies to understand the costs and benefits of biomedical prevention. Several of these trials demonstrated fantastic successes and attracted positive press attention.

For example, a prospective cohort study that began in 2012 followed patients insured and treated by California hospital conglomerate Kaiser Permanente. The principal investigator, Jonathan E Volk, recruited and retained 972 participants for three years, and reported no new HIV infections across the board (Volk et al., 2015). These remarkably positive results contrasted those of trials conducted in the Global South, where even during shorter trial times, a significant portion of participants contracted HIV. An article published in September 2015 by the New York Times exalts the cohort study as great news for HIV prevention. The headline reads, ‘Insurer says clients on daily pill have stayed HIV-free’. In an interview for the article, Volk noted that participants were not required to give blood samples to test for serum concentrations of tenofovir that would prove adherence to the regimen. It didn’t seem necessary, as everyone enrolled in the trial had explicitly expressed interest to their primary care physician about receiving PrEP (McNeil Jr, 2015). Such claims suggest that when moved to the United States, Homo adhaerens is an attainable standard, a subject whom researchers can trust to be medically literate and compliant, unlike earlier experimental subjects in the Global South.

However, the Volk study also leveraged exclusion to produce meaningful results. Continuing the study for another year, Marcus et al. (2016) reported additional results regarding adherence, discontinuation and renal safety in the Journal of Acquired Immune Deficiency Syndrome. Overall, the results were similarly positive: 92% of participants had excellent adherence, and less than one percent were forced to discontinue PrEP because of low eGFR, an indicator of kidney health. However, closely reading the study reveals its narrow parameters. Over 97% of the study participants were men, and the majority of them were white and held bachelor’s-level degrees. In addition, 22.5% of participants discontinued their use of PrEP by the end of the study, women being two-and-a-half times more likely to stop than men. Most importantly, two participants who dropped out of the study and discontinued PrEP contracted HIV. There were important factors that contributed to their inability to participate; both of their insurance policies had lapsed, rendering them unable to participate in the study at Kaiser, or access Truvada.

As a demonstration project, the Volk study transformed Homo adhaerens from research subject to patient. To do this, the study relied on subjects to demonstrate responsibility through not only adherence, but active enrollment in an insurance plan and regular visits to the hospital.

Restructuring knowledge production: Learning from activists

Even after Truvada gained commercial success in the United States, randomized controlled trials of new HIV prevention drugs continue. Gilead has recently organized its own, independently funded, PrEP trial called DISCOVER. The RCT compares Truvada to the newer drug Descovy, which is half emtricitabine like Truvada, except contains a newer version of Truvada’s tenofovir DF (TDF) called tenofovir AF (TAF). Small safety studies have demonstrated that TAF is more potent at a lower dose, and as a result less toxic to kidneys and bones. Compared with early PrEP trials in Cambodia, Cameroon, South Africa, Botswana and other countries in the Global South, the DISCOVER trial is enrolling individuals from sites throughout the United States. As of April 2018, researchers have enrolled 5,000 men and transgender women who have sex with men; investigators are expecting results by 2021. The trial is taking place more than a decade after the first trials of PrEP took place, and just before the patents on Truvada’s two components, tenofovir and emtricitabine, will expire by 2021.

I use DISCOVER as a case study to understand how activists mediate and contribute to understandings of risk and adherence produced at the clinical trial. Historically, patient activist groups have become intimately involved in randomized controlled trials, often their only avenue to access unapproved and expensive new therapies. In a rich analysis of early scientific research in HIV therapy, Epstein (1996) argues that people with AIDS combined moral and scientific claims to create a unique expertise that gave them agency to negotiate study protocols. They advocated for clinical trials to have third arms – ‘parallel tracks’ that distributed expensive and unapproved drugs – and for the FDA to recognize surrogate endpoints (like CD4 cell counts) to conditionally approve lifesaving treatments that were stuck at the end of the development pipeline. People with AIDS famously exercised autonomy as research subjects, splitting doses and taking unapproved medicines concurrently, disrupting researchers’ statistical apparatuses. These grassroots techniques challenged the RCT’s double-blind comparison model.

Activists allege that the DISCOVER trial has been designed to deny activists and advocates a seat at the negotiating table. In fact, they suggest that DISCOVER constrains community involvement in order to expedite the approval of a new drug while patents on tenofovir and emtricitabine expire. Speaking with activists about their involvement with DISCOVER, I situate their campaigns, tactics and goals in terms of Homo adhaerens. Similar to Krellenstein’s earlier criticism of subgroup analysis, which debases the scientific grounds on which the figure was first constructed, many activists involved in the DISCOVER trial rebuke the assumptions and prescriptions of Homo adhaerens. My analysis centers around two face-to-face meetings, during which advocates pressured Gilead to eliminate two inclusion criteria: one that prevents subjects from using PrEP before the trial begins, and another that demands high-risk behavior.

Many activists’ attention to DISCOVER began in the summer of 2016, when they encountered the clinical trial for the first time on the US government-run database ClinicalTrials.gov. One activist with whom I spoke, for example, first heard that the trial had begun to enroll participants in July, while travelling to the World AIDS Conference. Reeling from surprise, a small group of activists secured a meeting with Gilead to discuss several concerns. They were particularly bothered that Gilead had, in their view, not meaningfully involved the community, and they saw problems with the trial that were reminiscent of the first cancelled PrEP trials of Cameroon and Cambodia. Of the prompt meeting, Anna Forbes and Marc-André LeBlanc for TheBody.com, an activist media outlet, write, ‘we raised serious ethical and logistical concerns about the trial design, duration, enrollment criteria, informed consent and other issues on which community input would be valuable’ (Forbes and LeBlanc, 2016).

The gathering was followed by a larger meeting in September, held at AVAC’s headquarters in New York City. For about two hours before the meeting, activists prepared and discussed their demands independently. After Gilead arrived, a discussion of issues began. One of only two European activists present was Will Nutland, the founder of PrEPster – an organization that disseminates information about PrEP in the United Kingdom. Nutland described the meeting as at times very cordial, but at others erupting into dispute. Most of the engagement between Gilead representatives and activists happened in small corridor-style breakout meetings.

To kick off the meeting, activists insisted that Gilead meaningfully engage the community in all aspects of the clinical trial by establishing two Community Advisory Boards (CABs), one for the North American trial sites and one for those in Europe. The HIV Prevention Justice Alliance issued an open letter demanding that Gilead ‘[i]mpose a temporary halt to enrollment of and withdrawal of current marketing materials for the DISCOVER trial’ (HIV Prevention Justice Alliance, 2016). After the letter was signed by over 40 organizations, Gilead convened two Community Advisory Boards that continue to meet as the trial progresses. However, the CABs don’t allow participants to question the general direction of PrEP research or change any of Gilead’s overall goals.

The second demand that activists levied during the meeting was that Gilead eliminate the 30-day ‘washout period’, a requirement that participants stop taking Truvada before enrolling in DISCOVER. If not repealed, prospective subjects who had become accustomed to using Truvada would have to relinquish their primary prevention tool for a month. This would create a gap between prophylactic regimens, leaving participants without a familiar risk-reduction method and potentially vulnerable to HIV. Responding to community pressure, Gilead repealed this requirement. Activists also complained that Gilead required recruits to have had condomless sex with at least two unique male partners in the previous three months (not including partners known to be HIV negative) or to have been diagnosed with a sexually-transmitted infection in the previous two years. This complex criterion serves as a reminder that while PrEP trials include risk-reduction counseling as a component of their intervention, they also explicitly target individuals they know to be at risk. In these two conflicting requirements, the DISCOVER trial highlights the danger of Homo adhaerens – before it was repealed, the 30-day washout period in combination with the behavioral risk criterion would have exposed prospective participants to HIV. By successfully demanding Gilead remove the 30-day washout period, activists mirrored strategies of previous generations who questioned rigid scientific practices that made it difficult for patients to access drugs. In this case, calling into question the tenets of Homo adhaerens, activists also criticized the conflicting standards of conventional responsibility to which an ideal subject of biomedical HIV prevention research is held.

Despite their successes in negotiating the trial protocol and community involvement, activists were excluded from participation in recruitment. In the United States, Gilead outsourced the trial’s clinical labor to a mix of large hospitals, like Weill Cornell Medical College in New York, and much smaller clinics, many of which had never orchestrated a clinical trial. Activists were surprised that Gilead, inexperienced in running trials itself, expected trial sites to operate independently with very little oversight.

Each clinic developed their own set of recruitment advertisements using the limited information outlined in the study protocol. Despite Gilead’s policy to approve recruitment materials, Jeremiah Johnson, the HIV Project Director of Treatment Action Group, expressed to me his concern that smaller sites were ill-equipped. He noticed that many of the pamphlets and posters distributed in the fall of 2016 framed the studies as real-world demonstration projects that distributed implicitly safe PrEP, obscuring the fact that participants wouldn’t know if they were given Truvada or Descovy:

They chose several different enrollment sites throughout the US and North America, including some sites that had never done this research before, some sites that are very, very small actually. And so, there was a sense of, ‘So, do you really have a handle on all of this?’ Do you really have people trained to do ethical recruitment? And of course, our concern was seeing some of these sites coming up with their own recruitment materials and my understanding is that it’s sort of site by site, they’re supposed to go through Gilead. A lot of this is sounding like they’re PrEP access, real world demonstration projects when of course you don’t know if you’re getting [Truvada] TDF/FTC.

Figure 1, a recruitment poster from a DISCOVER site in Orlando, Florida, advertises the ease with which an interested passerby can text ‘Sam’ to express interest in ‘taking a pill daily to prevent HIV infection’. Jim Pickett, an advocate from the AIDS Foundation of Chicago who shared the poster with me, said it was hardly the most egregious example. The colorful graphic suggests that the experiment is only open to ‘gay males[s]’, when in reality, the protocol states that the trial includes both men and transgender women.

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Figure 1.

Recruitment poster for PrEP study.

Because DISCOVER compares experimental PrEP to Truvada, participants are only incentivized to enroll in the trial by the possibility of accessing free PrEP, or in faith that the experimental drug confers additional benefits. Not only does DISCOVER contribute to naturalizing Homo adhaerens by attempting to implement a 30-day washout period and demanding condomless sex – two requirements that discipline and expose prospective trial participants – it recruits a sample of patients who are enticed by claims that ‘study medication … [is] provided at no cost’. In doing this, DISCOVER folds the early conception of Homo adhaerens – the contradiction of risk and adherence initially forged in the Global South – into the Volk study’s findings that PrEP is only successful in patients with adequate social and financial capital. The ideal research subject in DISCOVER, a vulnerable patient to whom Truvada is otherwise inaccessible, is not the ideal patient. For biomedical HIV prevention research to prioritize participant safety, produce knowledge valuable for those who are most vulnerable, and actively engage the community, it must first be detached from Gilead’s incentive to expand their pharmaceutical franchise.

Conclusion: PrEP in the contemporary moment

The project of creating and refining Homo adhaerens through randomized controlled trials, demonstration projects, and cohort studies continues to the present moment. At the World AIDS Conference in 2018, Sarah H Browne (2018) from the University of California, San Diego (UCSD) unveiled preliminary results from tests of a technology called ‘digital PrEP’. Brown embedded a sensor in oral PrEP tablets that sends a signal to a patch on the patient’s skin when PrEP has been ingested. The patch, in turn, notifies the patient’s physician through a mobile phone application. Physicians, who are tasked with disciplining patients to adhere, were excited that 92% of users were satisfied with the device. Along the same lines, Moore et al. (2016), also from UCSD, tested the effectiveness of sending a tailored text message to improve patients’ adherence. In a poster presented at the 2016 AIDS Research and Human Retroviruses conference, the team demonstrated that those who were randomized to receive ‘individualized texting for adherence building’ had ‘significantly higher, near perfect adherence’ (Moore et al., 2016). Since 1969, when Walter Aven was granted a patent for the Calendar Reminder and Dispensing Device, biomedicine has continued to imagine technologies that intervene on the anatomo-politics of the body, finding new ways of locating the burden of adherence on the individual.

Contrary to the atomizing lens of clinical research, activists opt to understand adherence in terms of health care insecurity. As the Volk et al. (2015) study highlights, loss of insurance or access to PrEP can prevent patients from continuing use, exposing them to HIV. Activists, who also draw our attention to the fact that research on tenofovir and emtricitabine was publicly funded by the NIH, demand more of Gilead. They claim that the company’s co-pay assistance program, which offers to pay a maximum of $3,600 per year per patient, leaves those holding the average bronze health insurance plan $2,000 short of their deductible. Emphasizing Gilead’s obligation to make Truvada accessible, Jeremiah Johnson told me that:

Gilead should be doing a lot more with their co-pay assistance program, [such as] working with communities to ensure that their co-pay assistance program and medication assistance programs are meeting the needs of the ridiculous price of Truvada to make sure that these community are gaining access.

As an attempt to eliminate the monopoly that allows Gilead to charge such high prices, activists also rally around the idea of approving a generic drug. Ideally, generic drugs are cheaper and biologically equivalent to their proprietary counterparts, giving payers another option. However, activists also suspect that Gilead has offered settlements to generic drug manufacturers to temporarily extend their period of patent exclusivity. To circumvent this delay, activists have drawn my attention to Cimduo, a PrEP drug composed of two off-patent molecules that has been approved for HIV treatment. Both Truvada and Cimduo are made up of half tenofovir, but where Truvada has emtricitabine for its other half, Cimduo has lamivudine. Cimduo’s combination however, would be about 40% cheaper than Truvada, and possibly similarly effective. While it is unlikely that Mylan will fund a large RCT to test Cimduo’s efficacy for PrEP, the prospect of a community-based clinical trial is exciting and should serve as an opening for future social scientific inquiry.

Truvada discourse has also been rife with discussion of ‘breakthrough infections’, instances in which patients, despite adhering perfectly to PrEP, contract HIV. In the winter of 2017, media outlets reported that an anonymous man on PrEP in the Netherlands had been diagnosed with HIV. Because he was enrolled in the Amsterdam PrEP (AMPrEP) study at the time of his seroconversion, researchers were able to determine that he wasn’t HIV positive before beginning the trial, and that he had adhered excellently to the prophylactic regimen as the trial progressed. The only thing researchers found exceptional about the man was his number of reported unique sex partners. According to a case study poster that the AMPrEP team presented at the Conference on Retroviruses and Opportunistic Infections in Boston, the man had reported over 50 (mostly unprotected) sex partners per month on average (Hoornenborg and de Bree, 2017). The researchers hypothesized that his risky behavior was the reason that Truvada had failed him; high viral load from multiple partners manifested as a local infection in his rectal tissue, lingering until it became systemic hours later when his serum drug levels had decreased. By embodying a high risk for HIV, and being committed to taking Truvada every day, the Amsterdam patient was the mirror image of the individual extracted in early clinical trials. In other words, he was a material manifestation of the figure of Homo adhaerens.

A year later, in March 2018, headlines declared that a resistant strain of HIV had gained footing in another man’s body, rendering the Truvada to which he was adherent useless. Most media reports of the incident expressed surprise, destabilizing the idea that Truvada is a magic bullet. One source called the event, ‘[a] rare case of HIV transmission in King County [that] appears to be resistant to a so-called miracle drug’ (Horne, 2018). Ultimately, however, the coverage struck a positive note, reminding readers that Truvada is over 90% effective when taken daily, and that resistant strains have not proven to be a concern.

These moments of technological failure demonstrate biomedicine’s fascination with magic bullet, miraculous, fixes. In both narratives, the tragic figures are cast as unlikely victims of a virus that can be avoided through adherence to PrEP or prudent risk mitigation. Unlike the patients who disappeared from accounts of Volk’s et al. (2015) cohort study but later contracted HIV, these figures draw attention because they are Homines adhaerens. The unfortunate consequence is that focusing on technological failure primes Truvada for high expectations and obscures the structural inadequacies that plague HIV prevention.

The crux of these snapshots of the contemporary moment, and PrEP discourse at large, is individual responsibility. By visiting multiple sites of clinical research – from iPrEX in Latin America, to the unveiling of digital PrEP at the University of California, San Diego – I have delineated how a coalition of stakeholders constructs, contests, and naturalizes understandings of risk and adherence. The analytic figure of Homo adhaerens, which I have used to develop this understanding, emphasizes that way that PrEP research creates and provincializes a universal body. Homo adhaerens is at once an ideal subject created and transformed by clinical researchers to standardize knowledge production, a very real expectation levied on patients, and a place at which activists intervene to engage with clinical trials. The implications of this figure have already been realized. PrEP cannot offer a miraculous end to the HIV epidemic without being situated in a larger context that attends to effectiveness, stretching conceptions of adherence, discipline, and risk beyond the individual body. In order to achieve this broader focus, we can learn from activists, who seek to make large-scale structural changes to PrEP access and expand recruitment in clinical trials. Likewise, effective activist campaigns must approach Homo adhaerens from both ends – challenging the idea that individual patients should be the unit of biomedical analysis and insisting on the widespread availability of PrEP.