by Sophie Rosenmoss
When acquired immune deficiency syndrome (AIDS) first emerged as a public health crisis, daring to hope for a treatment may have seemed futile to those living through the epidemic. But the introduction of highly active antiretroviral therapy (HAART) transformed human immunodeficiency virus (HIV) from a death sentence into a chronic, manageable condition for those with adequate access to care. In the past decade, the drugs that revolutionized treatment have begun to shape prevention as well; clinical trials have demonstrated the efficacy of using antiretroviral therapy (ART) to prevent the transmission and contraction of HIV. This form of prevention therapy, known as pre-exposure prophylaxis (PrEP), offers a promising new option for individuals at risk for HIV infection. Despite the demonstrated safety and efficacy of PrEP as a preventative agent, effective implementation of the therapy presents a wide range of challenges and discourse surrounding the drug has varied between and within communities. In general, issues surrounding PrEP fit into two categories: the controversies about the risks PrEP may pose to individuals and to communities and the structural, social, and cultural factors that serve as barriers to effective and ethical dissemination and uptake. Decisions regarding where and how to scale up the use of PrEP must consider the dynamic social, cultural, and structural factors that will affect the intervention’s acceptability, feasibility, and ultimate impact.
The approved form of PrEP, the oral medication Truvada, is a combination tablet containing tenofovir disoproxil fumarate and emtricitabine, two nucleoside reverse transcriptase inhibitors (NRTIs).1 Reverse transcriptase is an enzyme required for the transcription of viral RNA into DNA, which is then incorporated into the host genome. NRTIs impede the activity of reverse transcriptase by binding to the enzyme’s substrate—in this case the DNA chain being transcribed. By adding themselves to the growing DNA chain in place of a nucleoside, NRTIs cause chain termination, halting transcription and preventing the replication of HIV infected cells.1, 2 Several studies have demonstrated Truvada’s effectiveness in reducing HIV infection in high-risk populations. The Pre-exposure Prophylaxis Initiative (iPrEx) trial showed that consistent use of an emtricitabine and tenofovir disoproxil fumarate combination pill reduced rates of infection by 92% in gay and bisexual men and transgender women who have sex with men.3 Additionally, a study on heterosexual HIV transmission in Botswana found PrEP had an efficacy of 62% in male and female populations.4 Evidence from these and other randomized controlled trials and observational studies led the Food and Drug Administration to approve emtricitabine/tenofovir disoproxil fumarate combination therapy for prophylactic use in 2012.5 In 2014, both the World Health Organization and the Centers for Disease Control released recommendations for the use of PrEP in populations that are likely to benefit from the medication.6, 7 Although efficacy results have varied between studies, the cumulative research on PrEP demonstrates the method’s potential to reduce the incidence of HIV.
The sound biology behind PrEP, the publicized clinical trials, and the national and international regulatory body endorsements, however, show only one side of the complex reality that is implementation across populations. Firstly, public and professional perceptions of risk have stigmatized PrEP, affecting attitudes towards the intervention. In the United States, concerns surrounding PrEP have focused on risk compensation, a practice by which an individual substitutes one preventative health behavior for another. 8, 9 In the context of PrEP, some argue that patients will use PrEP as a replacement for condoms and will engage more regularly in high risk behavior. This fear has been particularly salient in discourse surrounding PrEP, as numerous studies have found the degree of protection that PrEP provides to be dependent upon the patient’s adherence to the drug regimen. 3, 4, 6, 9 Thus, the risk compensation argument asserts that foregoing condoms could mitigate the effects of PrEP unless the patient maintained maximum adherence to the drug. Additionally, PrEP offers no protection against other sexually transmitted infections, meaning that decreased use of barrier protection methods might increase incidence of other infections.8,9 The debate around increased risk-taking behavior has been markedly pervasive amongst men who have sex with men (MSM), who make up a primary market for Truvada in the United States.8,10
While risk compensation and decreased inhibition arguments make intuitive sense, their focus upon recklessness and even promiscuity makes the assumption that all individuals share the same initial notion of “safe sex.” While widespread condom use, accurate disclosure of HIV status, and informed and cautious sexual practices are goals towards which public health efforts should work, the presumption that these are ideals towards which everyone strives may not be realistic. Regarding PrEP, fears of increased sexual risk behaviors fail to recognize that the individuals who choose to use PrEP may have had inconsistent condom use before initiation of the drug.8,10 By offering an alternative protective option to those who are already at a high risk of infection, clinicians and public health officials mobilize the principles of harm reduction. This approach to public health aims to minimize the consequences of risky behavior, thus focusing on reducing HIV incidence overall without imposing value judgments regarding behavior. PrEP as a tool for harm reduction may provide a sustainable addition to public health programs that aim to decrease the burden of disease at a population level.
Despite the value of a harm reduction approach, pragmatic dissemination efforts should nonetheless continue to emphasize the importance of utilizing a comprehensive, holistic set of HIV prevention strategies. Numerous PrEP trials have attributed instances of low efficacy to insufficient adherence, meaning that participants skipped doses, took their medication sporadically, or stopped the medication for periods of time.3, 4, 6, 9, 11 This means that decreased medication adherence decreases patients’ protection against HIV, increasing their chances of infection upon exposure to the virus. Public health marketing of PrEP should emphasize the imperfect nature of the product and the importance of complying with a medication schedule. This could unfold in creative ways; one study suggested the use of “adherence buddies” in communities where PrEP implementation is underway.11 The paradigm of combination prevention 18 should remain at the forefront of efforts to scale-up PrEP as a standard intervention. PrEP should not replace condoms—which not only help close the gap between PrEP’s adherence-dependent success rate and a total prevention of HIV but also protect against other STIs and unplanned pregnancy. Additionally, serodiscordant couples may choose to add PrEP to a regimen that includes treatment-as-prevention (TasP). TasP capitalizes upon the fact that initiating ART starting soon after infection decreases one’s viral load, making the HIV positive patient less infectious.18 In fact, some serodiscordant couples conceptualize PrEP as a “bridge,” using the regimen to protect the seronegative partner until the seropositive partner has used ART to achieve a minimal viral load.12
From an anthropological perspective, however, the assumption that holistic prevention practices are universally accessible may reflect a moralistic view of sexuality that ignores the social and structural factors constraining agency. Inequality, poverty, and social norms influence sexual practices within various contexts. In The Politics of Prevention: A Global Crisis in AIDS and Education the authors discuss the ways in which power dynamics and poverty can limit an individual’s options and increase one’s vulnerability to HIV.13 Gender inequalities and normative roles in society influence how sexual encounters are navigated and how condom use is negotiated, meaning that the playing field is not always even.8, 13, 14 Poverty can also influence sexual risk-taking in areas with high incidence of HIV. 13, 14 For example, female sex workers in Kenya and South Africa cited earning a greatly increased amount of money from unprotected sex than from encounters in which the client used a condom.15 Female, male, and transgender sex workers in the United States experience similar pressures to engage in unprotected sex, from financial desperation as well as the unequal power dynamics they experience.16 Both of these populations have high rates of HIV infection.15, 16
Thus the rationalist framework of prevention upon which morally based arguments are based is flawed in that it assumes that all parties have control over their risk-taking behavior. It fails to acknowledge the heterogeneous, nuanced, and potentially transactional nature of interpersonal interactions. For populations and individuals who are limited in their options for protection against HIV, PrEP may present a new source of agency.8 Perhaps mirroring the ways in which choices in contraceptive methods allow greater adoption of pregnancy prevention practices, a new delivery method for HIV prevention may provide vulnerable populations a form of protection that fits into their reality.8,15 Perhaps it would allow for privacy and individual planning, shifting control from the partner (who may determine whether or not a condom is used) to the individual who desires protection against HIV.
Another form of stigma conflates patients who take PrEP with those who are HIV positive, thus serving as a potential deterrent to uptake and adherence. Patients with HIV use Truvada as part of their HAART regimen, and the pill has gained a reputation as a symbol of seropositivity.8 MSM in New York City expressed fear that they might be stigmatized despite their negative serostatus.17 Furthermore, a deeper theme of the conflation of MSM sexuality with HIV may pervade, 8, 17 adding to fears around the consequences of taking ART for prevention rather than treatment. This demonstrates the importance of understanding how ingrained, historically charged symbols and concepts can influence health behaviors, which in turn will determine the success of prevention campaigns. The VOICE-C qualitative study in South Africa noted a similar phenomenon by which family and friends would assume a study participant was in fact HIV positive, as the “little blue pill”8 has become closely associated with the virus.11 Within the community participating in the study, Truvada was not viewed as a medication for healthy bodies, but rather as indexical of disease. Its use as a preventative agent disrupted accepted understandings of health, disease, and treatment.11 Within this cultural framework, it is not surprising that many women cited lack of familial support and even ostracism as contributors to low medication adherence. Since adherence to PrEP is intimately linked to the medication’s efficacy, the study was not successful in demonstrating PrEP’s effectiveness.11 Thus, the success of this pharmacological intervention in certain cultural contexts will depend heavily upon social acceptance and endorsement of the drug. Despite the biomedical nature of the prevention tool, social structure and cultural values will greatly influence its implementation.
Finally, PrEP’s overall impact will depend upon whether the most vulnerable populations gain access to the intervention. Although HAART has dramatically reduced HIV-related mortality in many industrialized areas, the majority of HIV-infected patients live in developing countries.18 High prevalence of HIV in these regions increases likelihood of exposure to the virus, particularly in environments where TasP practices may be inconsistent. Once infected, patients in low-income countries often lack access to ART, leading to increased AIDS mortality. 18, 19, 20 This link between poverty HIV infection is not restricted to countries with limited health infrastructure; low socioeconomic status has been associated with positive HIV status in the United States, where HIV prevalence in low-income urban areas is inversely related to socioeconomic status. 21 PrEP could provide a powerful tool for impoverished populations in the United States and abroad and efforts to incorporate these drugs into global HIV prevention efforts should tailor campaigns to meet the needs of these groups. The high cost of the emtricitabine/tenofovir disoproxil fumarate combination pills has been a barrier to widespread uptake, but provision of PrEP amongst high-risk populations may present a more cost-effective option than lifelong treatment of HIV infection. 22 The adherence and medical monitoring that a PrEP course requires could create another challenge for individuals without regular access to primary care. Successful programs to implement PrEP within these communities must develop strategies to make adherence and follow-up feasible. Additionally, the development of long-lasting implants, injections, and even drugs with longer half-lives may increase PrEP’s acceptability and effectiveness in resource-poor environments.15, 23 In settings where inconsistent adherence is a concern, emphasis on the use of condoms and other prevention methods in combination with PrEP will be essential.
Despite its complexities, PrEP offers a novel method for protecting individuals against HIV infection and reducing the burden of disease on national and global scales. But in the transition from clinical trials to implementation, public health officials must consider the social, cultural, and economic contexts within which the drug is disseminated. The way PrEP is received, understood, and utilized will not be universal, and will depend instead upon varied social and cultural norms of sexuality, health, and disease—as well as circumstances and values that vary between individuals. Additionally, local health infrastructure and availability of resources will influence which methods prove effective, meaning that structural factors must be considered. Adherence facilitators and constraints will differ between and within communities, and efforts to ensure effectiveness will require tailored, locally influenced planning. There are many forms of vulnerability and varied conceptions of prevention. Thus, efforts to protect those at risk must accommodate this heterogeneity, promoting PrEP as one component within a comprehensive, customizable package of prevention methods. PrEP offers a valuable lesson in the difference between clinical efficacy and population-level feasibility. It demonstrates the importance of incorporating implementation analyses into public health research and policy and foregrounds the substantial impact of sociocultural factors upon health outcomes.
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