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Para-States and Medical Science

Making African Global Health

Duke University Press

Treating to Prevent HIV: Population Trials and Experimental Societies

Vinh-Kim Nguyen

This chapter explores how Africa has emerged at the heart of global biopolitics in ways that drive biomedical research and the development of new health interventions. Novel approaches to intervening on human populations are currently being fashioned through population-based experiments, with potentially remarkable biological and social results. The focus of this chapter is the emergence of a breakthrough in addressing HIV: the ability of mass treatment to potentially eradicate the epidemic. Treatment as prevention (TasP) is this new strategy. TasP was cobbled together from already existing science and is now the subject of over fifty large studies around the world and is the subject of this chapter (Granich et al. 2011). My suggestion is that these large trials of treating-to-prevent herald the birth of experimental societies: large-scale forms of social organization assembled on biopolitical terrains left fallow by retreating states. This happens when experiments deploy a form of governmentality that leaks, through space and time, outside the trial. Under the right circumstances, residues of protocols, procedures, discursive practices, experimental biologies, and embodied experiences may congeal to constitute experimental societies. The para-state is visible as a kind of shadow of the experimental society: both cause (as a zone of abandonment [Biehl 2005]) and effect (as an assemblage of evidence-driven interventions, mobile governmentalities). Let me begin by setting the stage, before turning to examine the genesis and origins of TasP.

In July 2010, the Eighteenth International AIDS Conference was held in Vienna. Host cities are chosen by a complex calculus that includes geographic representation, receptivity to the messages of the AIDS world, and a reading of which strategies must be given a boost. Hence the slogans sported by each conference: in this case, "Rights Here Rights Now." Vienna was a geographical proxy for Eastern Europe, and the issue of human rights was a particularly timely one in this part of the world, where the AIDS epidemic was growing faster than anywhere else, largely driven by an epidemic of intravenous drug use fuelled by a toxic combination of postsocialist social breakdown and abundant, cheap heroin flowing out of post-Taliban Afghanistan (Beyrer 2010). The link between the epidemic and the historical geography of state failure in the postsocialist world contrasted with that in Africa, where arguably the state never had the same material presence. In Eastern Europe the tendency to criminalize drug use was viewed with concern by the organizers of the conference. They justifiably argued that fighting drug use with repression violates the rights of drug users, most notably their right to mitigate the deleterious effects of drug use through "harm reduction" such as methadone substitution therapy. Of considerable public health concern was the fact that, in this part of the world, prisons were in fact epidemiological pumps, concentrating those most vulnerable to HIV in one place and thereby facilitating the spread of HIV and its companion infections, such as tuberculosis. In this view drug use was a medical problem, not a legal issue, and human rights is the right treatment. While in Eastern Europe there was too much state, in Africa there was not enough.

The focus on "rights here" (that is, Eastern Europe) and "right now" (that is, as the epidemic explodes in this part of the world) blurred during the conference, which went noticeably off message from the get-go. The culprit: TasP, an idea that had been making the rounds over the past year in obscure epidemiological articles and had now burst into the limelight. The concept of TasP is simple. When people infected with HIV are administered powerful antiretroviral (ARV) drug cocktails, their "viral load" (the quantity of virus in the blood) drops to undetectable levels. As a result, they become much less infectious. In this view, if everyone who is HIV positive is treated, no more HIVtransmission—and no more epidemic. (I will return to this supposition a bit later.) While many factors account for this shift, my discussions with scientists and policy makers at the time suggested that the global geopolitics of HIV was driving the push for TasP.

Because it bears the brunt of global HIV infections, it is in Africa that the success of the response to the epidemic is measured; it is where international donors have invested the most and correspondingly have the most at stake. This was not always the case: the epidemic was first recognized in the United States and rapidly described in Europe, where robust health systems were able to detect the epidemic early. Recognition of the epidemic's severity in Africa lagged, partially because a patchy, poorly funded and equipped health system (a symptom of state weakness) was ill-equipped to differentiate AIDS from the common diseases that ravaged the continent. Until ten years ago, the technoscientific response was mainly driven by the needs for addressing the epidemic in the north, and it was possible to see—and denounce—a "two-track" approach to the epidemic: individualized prevention and treatment for the north, and collective prevention and palliative care for Africa. After the Durban conference, the two-track approach was officially abandoned, such that treatment was deemed a priority for the developing world too. In Africa massive treatment programs were scaled up and millions put on the antiretroviral drugs.

By 2008 concerns began to be raised that treatment was occurring at the expense of prevention programs (for an overview see Merson, O'Malley, Serwadda, and Apisuk 2008). These concerns were motivated by alarming reports that the incidence of HIV was increasing in some gay men in the north, where prevention had until then been a resounding success, and that it was not decreasing appreciably in the south. It would not be possible, we were ominously warned, to "treat our way out of the epidemic." Backstage, the concerns were more strongly worded. The lion's share of the funding was going to treatment: expensive but with easily measured results that could be marketed using the powerful metrics of "lives saved." Prevention was no longer appealing, and donors were no longer interested. Nowhere was this clearer than at the epicenter of the epidemic, where the human, financial, and geopolitical stakes were high. As some had feared, the biomedical lobby had "hijacked" the HIV train. The arrival of TasP, two years later, was an opportunity: prevention and treatment could be reconciled, and perhaps a breakthrough appeared where prevention alone had had only limited success.

Biomedical Prevention: New Technologies, Old Issues

TasP was but the latest salvo in the deployment of biomedical prevention, so-called because it involves the use of biomedical technologies to prevent HIV, rather than behavior change or condoms (Rosengarten et al. 2008 alerts to the challenges involved; for a recent review, see Padian et al. 2011). Such biomedical technologies include the use of drugs to prevent infection, either applied locally as microbicidal gels or taken prior to or after sexual exposure: respectively, pre-exposure prophylaxis (PrEP) and post-exposure prophylaxis(PEP). Circumcision of males has been shown to protect men against HIV and has joined the armamentarium of biomedical prevention as medical circumcision programs are ramped up. Within the AIDS industry, these approaches are referred to as the "new prevention technologies" (NPTs). It must be underlined that most of these NPTs have been developed mindful of the particular epidemiological realities of HIV in Africa, where it is widely accepted that HIV is largely heterosexually transmitted, gender norms make women particularly vulnerable and men resistant to older behavioral prevention approaches, and a generalized epidemic dictates measures targeting the entire population rather than focused "high-risk" groups. (It is also worth underlining that these assumptions themselves reveal a certain tendency to homogenize and stereotype a highly diverse continent and its social realities as a kind of mirror image of the West. The recent "discovery" that men who have sex with men are of epidemiological importance in Africa and that gender norms are in fact far more mutable than previously assumed are two examples that argue against this simplistic view.) Biomedical research in HIV had up until then largely focused on the north, but biomedical technologies are now being engineered specifically as a function of Africa's (perceived) epidemiological specificities—and tested there for eventual re-export back to the rest of the world.

Post-Vienna, the stress on TasP and other NPTs seemed to be redefining HIVas a purely medical problem best left in the hands of doctors and scientists. Backstage, it was possible to detect exasperation with the messy world of unruly subjects, refractory gender norms, unreasonable activists, and noncompliant states (see Lachenal's chapter on medical nihilism in this volume). That impatience reflected the difficulty in finding a simple, technical fix to the otherwise challenging problem of prevention, mired in issues of gender, power, and poverty.

Searching for a Magic Bullet: From Vaccination to Mass Treatment

A vaccine in contrast promised a simple, technical fix to the seemingly intractable issues that dogged HIV prevention—a magic bullet. There would be no need to change behavior, no need to target specific groups, no risk of incurring the wrath of activists. Vaccine trials, however, have not borne out these hopes. For instance, in the wake of the highly visible failure of the STEP trials in 2007, leading scientists and the NIH proclaimed that it was "back to the drawing board." An important point however is often glossed over, perhaps because of the pervasiveness of the idea of the vaccine as a magic bullet. Because of the way HIV, and the immune system, interact, it is highly unlikely that any vaccine would confer the kind of total immunity that we associate with usual vaccines—for mumps, measles, rubella, hepatitis, and the like. So if an HIV vaccine is not fully protective, that is, only reduces the risk by say 50 percent or so, this has several implications. The first is that a very large number of people will have to be vaccinated for the vaccine to have a notable effect at the population level. This is referred to as "herd immunity": once a certain threshold of the population is immunized, the infectious disease effectively dies out because not enough susceptible individuals are left in the population to ensure a chain of transmission. When vaccines are 100 percent effective, they will protect a population once 75 or 80 percent are immunized. This will not be the case for HIV unless an unforeseen breakthrough occurs.

The presumed weakness of HIV candidate vaccines has several implications. First, that the clinical trials needed to demonstrate their effectiveness will need to recruit comparatively larger numbers of subjects to prove—or disprove—efficacy. A second, related point is that should a marginally better vaccine come along, even larger numbers will be required to tease out the relatively small differences in efficacy between the vaccine candidates, driving up the cost of subsequent trials for ever-diminishing preventive returns. In other words, it is unlikely that an eventual HIV vaccine would actually be a magic bullet.

Given the paucity of promising results on the vaccine front, it is not surprising that other approaches have been tried. Early awareness that gender dynamics made condom use problematic, particularly in Africa's burgeoning heterosexual epidemic, spurred the search for female-controlled methods such as the female condom and microbicides (Hardon 2012). Microbicides were touted as the next best thing to a vaccine, but hope quickly gave way to pessimism as trial after trial showed disappointing results, with some even suggesting that microbicides could increase HIV transmission (e.g., Van Damme et al. 2002; Gawrylewski 2007; for a recent editorial overview, see Quiñones-Mateu and Vanham 2012). It was amid this global gloom that good news sprang seemingly out of nowhere in 2007. Male circumcision, it was convincingly showed, resulted in a striking decrease in HIV incidence—on the order of 50 percent—in men circumcised in three different randomized clinical trials, relative to those left "intact." The only problem was that male circumcision does not protect women, at least in the short term. Its protective effect is therefore much like a vaccine given only to men: it will only protect the women once enough of the "herd" is vaccinated (WHO 2007). Male circumcision too is a population approach that dispenses with the need to engage with the messy world of human behavior, gender identity, and social constraint. But no magic bullet here either.

Another approach, which has generated considerable interest since 2008 has been PrEP. Initial optimism that PrEP might furnish a new tool in HIV prevention began in the late 1990s with animal studies that showed that treated monkeys with the antiretroviral tenofovir seemed to protect them when they were "challenged" with HIV (Tsai et al. 1995). Further support came from clinical trials of the antiretroviral drugs AZT and nevirapine, which showed that both could protect infants from acquiring HIV from their mothers during labor and birth. Eventually, trials of tenofovir as PrEP were begun in 2004 in Cambodia, Cameroon, and Malawi, with female sex workers as experimental subjects, only to be aborted by concerns that appropriate ethical standards were not in place. Eventually the ethical concerns were apparently addressed, and twelve trials are currently under way testing various antiretroviral combinations as PrEP, with a combined enrollment of thousands of patients. The trials generated intense interest after the Vienna conference, where a South African trial of PrEP with a tenofovir gel was shown to reduce incidence of infection by up to 50 percent in the women who used it (Abdool-Karim et al. 2010). Yet PrEP remains particularly prone to scientific and ethical challenges in testing as earlier controversies show. It is difficult not to view those who are infected in the context of a prevention trial as "victims" of that trial. As a result, the specter of those "failed" by prevention haunts these trials.

TasP dodges these issues, shifting the focus to those who might transmit rather than those who might be contaminated. Because potential transmitters are offered the benefit of treatment, there appear to be no "losers" when testing this approach. TasP comprises two similar approaches that differ in one important respect. The first, called test-and-treat, represents a public health, or population-based, strategy for controlling the epidemic (Cambiano, Rodger, and Phillips 2010). The most effective strategy would require automatic treatment of all individuals with HIV in a population. Such an approach would entail compulsory systematic testing and treatment, posing ethical challenges in pitting individual and collective interests. A more palatable alternative is to maximize testing and treatment through vigorous campaigns to incite testing ("increase uptake"). Importantly, those who test positive would then be treated with antiretroviral drugs, even if their condition does not warrant it.

The more conventional approach seeks to maximize testing and treatment but only treat if clinically warranted; that is, according to standardized guidelines that recommend treatment once the CD4 count (a measure of the immune system) is below a specific amount (in mid-2013 this threshold was increased from 350 to 500 cells/mL). This approach encourages testing and treatment, but treatment only if clinically indicated, and has been called various things from "expanded access" to "treatment 2.0" (WHO 2011). In this chapter I refer to both these approaches as TasP, which highlights the emphasis given to the preventive benefits of expanding treatment that is common to efforts to expand and intensify treatment efforts.

TasP thus comprises two strategies: the more aggressive test-and-treat strategy and more conservative treatment 2.0, which relies on increasing treatment coverage to achieve preventive effects. The former represents a classic public health approach to population health whereby ARV drugs are used even if not clinically indicated and therefore of no benefit to the person treated (the benefit of decreased transmission registers at the population level), while the latter is a clinical approach: treat only if warranted for the patient's health. TasP is not a scientific discovery that came out of the blue; rather it results from the cobbling together of existing pieces of science. These scientific building blocks were in place long before TasP was actually formulated as a strategy, suggesting that TasP's arrival on the international stage was at least partially in response to political and social circumstances rather than compelling scientific evidence that was already evident from the early 2000s.

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Excerpted from Para-States and Medical Science by P. Wenzel Geissler. Copyright © 2015 Duke University Press. Excerpted by permission of Duke University Press.
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