Clinical Uncertainties, Health Service Challenges, and Ethical Complexities of HIV “Test-and-Treat”: A Systematic Review

Abstract

Despite the HIV “test-and-treat” strategy’s promise, questions about its clinical rationale, operational feasibility, and ethical appropriateness have led to vigorous debate in the global HIV community.

We performed a systematic review of the literature published between January 2009 and May 2012 using PubMed, SCOPUS, Global Health, Web of Science, BIOSIS, Cochrane CENTRAL, EBSCO Africa-Wide Information, and EBSCO CINAHL Plus databases to summarize clinical uncertainties, health service challenges, and ethical complexities that may affect the test-and-treat strategy’s success.

A thoughtful approach to research and implementation to address clinical and health service questions and meaningful community engagement regarding ethical complexities may bring us closer to safe, feasible, and effective test-and-treat implementation.

ALTHOUGH WE HAVE SEEN significant progress in expanding HIV prevention and care services worldwide, an estimated 2.5 million individuals were newly infected in 2011.¹ Universal testing and treatment to prevent transmission of HIV has gained considerable interest from funders and international agencies as a potential public health approach to controlling the spread of the epidemic.^2,3 In a “test-and-treat” strategy, individuals would be routinely tested for HIV, and those who are identified as being HIV infected would be started on antiretroviral therapy (ART) immediately, irrespective of their stage of disease, to reduce their plasma viral load and thereby reduce their likelihood of transmitting the infection. Data from the HIV Prevention Trials Network (HPTN) 052 trial, which demonstrated a 96% reduction in transmission in HIV infection among serodiscordant couples treated immediately compared with those receiving deferred treatment, provided the needed scientific “proof of concept” for test-and-treat programs as an effective method of reducing HIV transmission.⁴ At the population level, in San Francisco, California, and Vancouver, Canada, new diagnoses of HIV and community viral loads declined in the years following expanded ART.^5–7 The mathematical modeling of Granich et al. at the World Health Organization in 2009 suggested that a universal voluntary test-and-treat strategy could virtually eliminate new HIV infections in South Africa within 10 years of its inception.⁸

Despite the test-and-treat strategy’s promise, unanswered questions about its clinical rationale, operational feasibility, and ethical appropriateness have led to vigorous debate in the global HIV community. We performed a systematic review of the scientific literature to identify the clinical uncertainties, health service challenges, and ethical complexities that may impede the success of a test-and-treat strategy. On the basis of our review, we have summarized uncertainties, challenges, and complexities we identified in the literature, and we have made research and implementation recommendations that should be considered to improve the likelihood of the test-and-treat strategy’s success.

METHODS

In May 2012, we searched the PubMed, SCOPUS, Global Health, Web of Science, BIOSIS, Cochrane CENTRAL, EBSCO Africa-Wide Information, and EBSCO CINAHL Plus databases for all articles pertaining to the HIV test-and-treat strategy. We used the following search term structure: (“test and treat” OR “universal testing” OR “universal treatment” OR “treatment as prevention”) AND (“HIV” [MeSH term] OR “HIV” OR “AIDS” OR “acquired immunodeficiency syndrome” [MeSH terms]). We included the MeSH terms in the search only in the PubMed database. We identified all such articles published beginning January 2009 through May 2012. We chose January 2009 as the starting point for article identification because that was the month and year in which Granich et al. at the World Health Organization published their seminal and widely acclaimed mathematical model that brought the HIV test-and-treat concept to international attention. A PRISMA⁹ statement for the full protocol was created and registered in the PROSPERO database, with registration number CRD42012002883.¹⁰

Article Selection

Two reviewers independently reviewed article abstracts and recommended them for full-length article review if the abstract subject pertained to HIV infection and met 1 of the following conditions: (1) mentioned “test-and-treat,” “seek, test, and treat,” “treatment as prevention,” “universal testing and treatment,” or “universal access to treatment”; (2) mentioned how the particular study’s findings have implications for the widespread implementation of HIV testing and immediate initiation of ART or the widespread use of ART as prevention; or (3) mentioned concerns or gaps in the evidence on the widespread implementation of HIV testing and immediate initiation of ART or the widespread use of ART as prevention.

We excluded articles if they were book chapters, were conference abstracts, had no listed author, or were not available in English. We excluded articles focusing solely on the use of antiretroviral (ARV) medications for preexposure prophylaxis, postexposure prophylaxis, or mother to child transmission to reduce HIV transmission or incidence as well as articles whose main outcome was something other than HIV transmission and incidence, such as tuberculosis incidence. When abstracts were not available or reviewers disagreed about whether the article met inclusion criteria, we referred the article for full article review. We again reviewed articles accepted for full-length review to determine whether they met the described criteria. We resolved differences between reviewers regarding whether an article met criteria by consensus after reference to the original article.

Data Collection Process

Two reviewers read full articles that met inclusion criteria and categorized them by study design into the following categories: empirical results from an experimental design, observational study, or mathematical modeling analysis; narrative or systematic review article; or commentary, including correspondences. Review articles included both systematic reviews and narrative reviews. We distinguished narrative reviews from commentaries by their aim to substantially review literature and evidence that identified critical points of the current knowledge on particular topics related to test and treat. Commentaries, which included short pieces and correspondences, included substantial argumentative points but did not attempt to summarize the literature on the topic of interest.

Reviewers also identified any comment in an article of clinical uncertainty, health service challenge, or ethical complexity that may impede the success of the test-and-treat strategy. The authorship team developed an a priori list of clinical, health service, and ethical themes to further describe each clinical, health service, or ethical comment in question. Reviewers labeled each identified comment with 1 of the themes. Reviewers also added themes to the list if the original a priori theme list did not adequately describe the uncertainty, challenge, or complexity in question. One reviewer combined both reviewers’ lists of thematically categorized comments into a single final list. The final list included the a priori list of themes along with all reviewer-generated themes. To identify and describe as many comments as possible, if only 1 of the reviewers noted a particular comment in a given article, we still included the comment and tallied it in the final list.

RESULTS

On the basis of our search strategy, we identified 207 articles (Figure 1). Of the 207 abstracts we reviewed, we excluded 84 because they were not relevant to the subject of review by our preset abstract review criteria. Of the remaining 123 citations we reviewed for inclusion, 1 was a book chapter, 1 was a conference abstract, 3 were not in English, and 4 had no author listed. Of the 114 full-length articles we reviewed, we excluded 16 on the basis of full-length article review criteria. Of the final 98 articles we selected for full-length review, 53 (54%) were commentaries, 28 (29%) were review articles, 11 (11%) were observational studies, and 6 (6%) were modeling studies (Table 1).^11–108 No studies contained empirical results derived from an experimental design.

FIGURE 1—

Summary of systematic review article selection process.

TABLE 1—

Systematic Review Article Type by Frequency: January 2009–May 2012

Study Type	Articles (n = 98), No. (%)
Empirical study
Experimental design	0
Observational design	11 (11)
Modeling	6 (6)
Review article	28 (29)
Commentary	53 (54)

The most frequently noted clinical theme was that published test-and-treat models showing the potential for HIV elimination, the Granich model in particular, are derived from uncertain or unrealistic assumptions (n = 27; Table 2). Many articles noted the concern that the test-and-treat strategy may lead to increased risk-taking behaviors among HIV-positive individuals who are on ART, thereby reducing the effect that early treatment would have on preventing secondary HIV transmission (n = 25). Another commonly noted uncertainty was related to the potentially significant role that acute HIV infection may play in the dynamics of HIV transmission at a population level (n = 20). The success of test and treat in appreciably reducing HIV incidence may depend on being able to identify acute HIV infection in a timely manner, a capability that is not feasible in most high-prevalence and resource-limited settings. Several mentioned the current lack of definitive evidence of early ART initiation’s benefit in individuals at the earliest stages of the disease as well as uncertainties related to potential long-term toxicities of ARVs (n = 20). ARV resistance was commonly noted as both a potential unintended consequence of expanded treatment and a factor that could eventually impede the ability of individuals to achieve viral suppression and therefore prevent transmission (n = 19). Nine articles noted that there is no evidence to date that early ART initiation results in reduced HIV transmission in couples or populations over long periods.

TABLE 2—

Themes of Uncertainties, Challenges, and Complexities by Frequency: January 2009–May 2012.

Theme	No.	References
Clinical uncertainties
Unrealistic mathematical modeling assumptions	27	12, 13, 14, 18, 19, 20, 36, 39, 41, 45, 53, 56, 60, 61, 67, 68, 69, 70, 79, 87, 95, 96, 97, 100, 102, 104, 105
Increased risk behaviors when receiving ART	25	3, 11, 20, 24, 31, 33, 53, 55, 57, 62, 63, 65, 66, 67, 68, 69, 75, 87, 91, 92, 97, 102, 104, 106
Acute HIV and role in transmission	20	3, 11, 23, 31, 33, 50, 57, 60, 64, 70, 71, 74, 90, 93, 94, 95, 97, 104
Benefits and risks of early initiation of ART	20	3, 16, 20, 24, 28, 29, 38, 39, 48, 50, 51, 53, 56, 57, 60, 61, 67, 72, 98, 102
ARV resistance	19	3, 20, 28, 29, 31, 33, 51, 53, 55, 57, 61, 71, 73, 87, 95, 97, 99, 100, 106
Durability of decreased transmission long term	9	20, 29, 32, 43, 51, 63, 71, 73, 100
Residual genital tract viral secretion	9	20, 28, 31, 53, 56, 64, 65, 66, 95
Role of concurrent sexually transmitted infections	8	31, 53, 63, 64, 65, 66, 87, 102
Penile–anal transmission	6	37, 43, 46, 56, 104, 105
Detecting treatment failure in resource-limited settings	6	35, 55, 71, 79, 103, 104
Health service challenges
Optimizing linkage and retention rates	30	3, 11, 14, 16, 19, 20, 24, 34, 37, 39, 43, 46, 51, 53, 56, 58, 60, 61, 67, 68, 87, 88, 96, 97, 98, 99, 100, 101, 102, 104
Optimizing HIV testing strategies	30	11, 13, 14, 16, 19, 20, 22, 24, 25, 34, 37, 43, 45, 46, 51, 52, 53, 60, 70, 71, 72, 74, 82, 83, 87, 96, 97, 98, 101, 104
Optimizing adherence to ART	23	6, 14, 20, 43, 45, 53, 56, 60, 61, 62, 63, 64, 65, 68, 71, 74, 75, 96, 98, 99, 100, 101, 104
Overcoming social and structural barriers	22	15, 21, 34, 37, 43, 48, 52, 53, 56, 57, 60, 61, 67, 68, 74, 77, 79, 80, 89, 99, 102, 106
Drug and program implementation costs	22	11, 20, 39, 46, 51, 53, 56, 57, 60, 61, 64, 67, 68, 74, 77, 79, 80, 87, 95, 97, 99, 102
Drug supply and second-line drug availability	9	23, 53, 61, 64, 74, 77, 79, 99, 103
Health care workforces issues	9	53, 57, 61, 70, 73, 79, 83, 102, 103
Ethical complexities
Resource allocation with scarce resources	22	3, 11, 15, 17, 23, 32, 41, 42, 44, 46, 48, 53, 60, 67, 68, 71, 74, 79, 94, 97, 99, 102
Balancing individual vs societal benefit	13	3, 15, 20, 23, 33, 42, 46, 49, 52, 71, 79, 99, 104
Coercion and informed consent	12	6, 15, 20, 32, 33, 40, 46, 53, 61, 84, 101, 102

Note. ART = antiretroviral therapy; ARV = antiretroviral.

Other, less commonly noted themes included evidence gaps concerning whether individuals who have undetectable plasma viral loads may in some scenarios continue to shed HIV in their genital tract and therefore potentially be infectious (n = 9); concerns about how unrecognized concurrent sexually transmitted infections can increase likelihood of HIV transmission and therefore potentially reduce the effectiveness of test and treat (n = 9); lack of evidence demonstrating effectiveness of early ART treatment in reducing transmission in populations of men who have sex with men or other populations with high levels of penile–anal sexual intercourse (n = 6); and concerns about how limited access to technologies to detect treatment failure in resource-limited settings may affect the ability of individuals in test-and-treat programs to achieve viral suppression (n = 6).

The vast majority of health service challenges noted in our review centered on the argument that without optimal linkage and retention (n = 30), optimal HIV testing strategies (n = 30), and adherence programs (n = 23) to ensure that HIV-infected individuals are identified, initiated, and retained in care and that they achieve viral load suppression, the test-and-treat strategy will not result in significant reductions in HIV incidence. Social and structural barriers, such as poverty, incarceration, substance abuse, and stigma, were also noted to be challenges to the implementation of the test-and-treat strategy in marginalized populations (n = 22). Drug and program implementation costs associated with widespread testing and treatment were commonly noted as a likely barrier to implementation (n = 22). Other challenges included capacity issues such as the current inadequacy of the health care workforce (n = 9) and drug supply systems (n = 9) in many of the most affected countries, which could impede timely availability of medical care and first- and second-line therapies.

The majority of the ethical complexities we identified centered on resource allocation issues (n = 22): the potential for the test-and-treat strategy to divert resources from other forms of HIV prevention, such as syringe exchange programs; from treatment of those who may need it most; and from other diseases or conditions. Another ethical complexity pertained to the tension that might arise as part of a test-and-treat strategy between an individual’s health benefit or treatment desires concerning ART and the public health benefit of reduced transmission from ART (n = 13). Finally, several articles included a concern that test-and-treat programs may be perceived or inadvertently carried out in such a way that individuals experience coercion or cannot exert proper informed consent (n = 12).

DISCUSSION

Our review of the HIV test-and-treat literature revealed numerous uncertainties, challenges, and complexities across the dimensions of clinical science, health services delivery, and ethics. Not surprisingly, considering the recent nascence of the test-and-treat strategy as a concept, fewer than 1 in 5 articles contained empirical data. Commentaries, which accounted for half of the articles, reflected the perspectives of experts and leaders in the fields of HIV treatment and prevention. On the basis of the findings of the literature review, we have proposed a strategic and thoughtful approach to research, implementation, and community engagement that will address the outstanding questions about and challenges to the test-and-treat strategy.

Clinical Uncertainties

One of the most critical questions concerning test and treat is whether the long-term benefit of early ART initiation to decrease HIV transmission outweighs the potential risks to the individual of long-term, lifelong treatment, such as drug toxicities and earlier treatment failure. Several ongoing studies will help answer some of the clinical uncertainties identified in this review (Table 3). The Strategic Timing of Antiretroviral Treatment trial and HPTN052 study will provide solid data in the next few years on the health outcomes for individuals receiving early versus delayed treatment.^107,108 The British Columbia population-based study Seek and Treat to Optimally Prevent HIV and AIDS will provide much needed data about the impact that expanded ART availability has on population HIV incidence.^109,110

TABLE 3—

Ongoing Test and Treat Research Studies: January 2009–May 2012

Study Name	Study Type	Pertinent Research Objectives and Findings	Timeframe
Population Effect of ART to Reduce HIV Transmission	Phase I: mixed methods study of feasibility and acceptability of comprehensive testing program in rural (Masaka, Uganda) and urban (Kabwe, Zambia) locations; pilot of immediate ART initiation to 100 newly diagnosed HIV patients	Examine uptake of test and treat, community engagement to enhance acceptability and human rights concerns, cost-effectiveness to inform design of cluster RCT; for pilot patients, examine adherence, viral load, CD4, OI, and drug resistance for 1 year after initiation; community HIV incidence	Phase I: 2010–2013 Phase II: 2013–
	Phase II: cluster-randomized trial of impact of treatment of all HIV-infected individuals
Treatment as Prevention	Phase 0: feasibility of providing universal testing and universal ART in South Africa	Examine best approaches to universal testing and universal ART to inform the design of cluster RCT; examine impact of ART on population HIV incidence, ARV resistance, HIV morbidity, adherence, adverse events, and high-risk behaviors and determine origin of new infections; examine population effectiveness and sustainability	Phase I: 2009–2011 Phase II: 2011–2015 Phase II: 2015–
	Phase I: cluster-randomized trial of impact of treatment of all HIV-infected individuals
	Phase II: expansion phase
National Institute of Mental Health Project Accept (NCT00203749)	Phase III: randomized control trial of community mobilization, mobile testing, same-day results, and posttest support for HIV in sub-Saharan Africa and Thailand	Examine efficacy of Community-Based HIV Voluntary Counseling and Testing (CBVCT) intervention plus standard clinic-based VCT (SVCT) or SVCT alone; CBVCT more effective than is SVCT in increased detection of HIV infection, especially in regions with restricted access to clinic-based VCT and support services after testing	Study completed in August 2011
Effectiveness of ART plus HIV Primary Care versus Primary Care Alone to Prevent Sexual Transmission of HIV-1 in Serodiscordant Couples (HPTN052)	Phase III: 2-arm, randomized control, multicenter trial of early ART in 1750 discordant couples in 8 countries	Measure impact of 2 treatment initiation thresholds; first arm initiated on enrollment, second arm initiated at CD4 ≤ 250 cells/mm3, on disease transmission, HIV progression, and ART toxicity; dramatic 96% reduction in HIV transmission in couples with early treatment announced in May 2011	Deferred treatment arm discontinued May 2011; data collection on secondary endpoints will continue through 2013
TLC-Plus: Feasibility of an Enhanced Test, Link to Care, Plus Treat Approach for HIV Prevention in US	Feasibility and effectiveness study of test and treat and strengthened linkage programs in United States (New York City and Washington, DC)	Examine impact of 4 components of community-focused enhanced test-and-treat strategy on prompt ART initiation, viral suppression, and high-risk behaviors	Enrollment began in 2010 and is ongoing; data collection to end 2013 or 2014
Strategic Timing of Antiretroviral Treatment	Randomized control trial of 4000 HIV-positive persons in 23 countries, minimum follow up 3 y	Compare immediate ART to deferred ART (CD4 ≤ 350 cells/mm3) for each component of the primary composite endpoint: AIDS, non-AIDS, or death from any cause	2009–2015; data collection will be complete 2015
Seek and Treat to Optimally Prevent HIV and AIDS	Phase III: population-based study of expanded ART availability in British Columbia, Canada	Measure impact of ART expansion on population HIV incidence at 3–5 y; secondary outcomes include AIDS morbidity and mortality, CD4 counts, viral load, drug resistance, safety, and health care utilization	2010–2013; data collection will be complete end of 2013

Note. ART = antiretroviral therapy; CD4 = cluster of differentiation 4; HPTN = HIV Prevention Trials Network; OI = opportunistic infection; RCT = randomized control trial; TLC = testing and linkage to care; VCT = voluntary counseling and testing.

Because rigorously derived data answering these questions are not anticipated for another few years, implementation efforts should first be focused on achieving universal testing and treatment according to current World Health Organization guidelines for the initiation of ART. Achieving this would be a giant step forward for the HIV epidemic in every country but particularly so in resource-limited contexts in sub-Saharan Africa. In addition, successfully implementing universal treatment according to guidelines will necessarily require addressing and finding solutions for many health service–related challenges that are also major barriers to effective test-and-treat implementation.

ARV resistance from expanded treatment remains a looming uncertainty that may affect individual and population outcomes. Although recent experiences in San Francisco and Vancouver suggest that transmitted drug-resistant strains in those communities have remained stable or decreased during the period when ART use expanded significantly, some researchers have shown through modeling the high likelihood for multiple ARV-resistant strains to evolve and replace wild-type strains with test-and-treat.^15,111–113 Populations starting treatment at earlier stages of infection as part of a test-and-treat strategy may have poorer adherence rates, resulting in a theoretically greater risk of resistance promulgation. At the same time, in most resource-limited settings, viral load quantification and genotype testing do not exist. To more accurately assess ARV resistance and detect treatment failures with universal treatment, many countries will require substantial investments in their health systems to build or strengthen components such as laboratory services and monitoring and evaluation systems.

Several clinical questions related to the real-world effectiveness of test-and-treat in reducing HIV transmission remain unanswered and underscore the need for ongoing research. There is emerging evidence of persistent HIV in genital secretions even when plasma levels are undetectable^17,114–115; whether this is clinically relevant to HIV transmission risk is still not well understood. Similarly, more research is needed to explore the role of concurrent sexually transmitted infections on HIV transmission and ascertain whether the potential threat of increased risk disinhibition among persons receiving ART exists and affects transmission. The efficacy of test and treat for sexual encounters that are predominantly penile–anal in nature is also not explicitly known from HPTN052, because the study population included few men who have sex with men.^7,43,104 Also, the contribution of the acute HIV infection stage, during which most patients are unidentified, untreated, and possibly participating in high-risk behaviors, to the maintenance and growth of the HIV epidemic is unknown and possibly very important.^33,90,104 Until these questions are better understood, it will be difficult to predict how effective test-and-treat will be in practice.

Health Service Challenges

We found that many of the most pressing issues facing the test-and-treat strategy are health services or implementation challenges, such as optimizing retention and workforce capacity. It is not uncommon once biomedical prevention strategies, such as treatment as prevention, are shown to be efficacious for questions related to long-term effectiveness in real-world settings to be sidelined as implementation challenges.⁶⁷ As a result, the important roles that systems, social contexts, and risk behavior play in enabling sustainable adoption of biomedical prevention interventions are inadequately acknowledged and inadequately researched, to the detriment of progress in the field.⁶⁷

A prime example of this is the lack of scientific knowledge on best practices to motivate HIV-positive individuals, especially those who are asymptomatic from the disease, to become and stay engaged in regular HIV care and remain adherent to ART over long periods. The International Association of Physicians in AIDS Care recently published guidelines for improving entry into and retention in care and ART adherence for persons with HIV in which it recommends systematic monitoring of entry and retention in HIV care; however, existing evidence-based interventions to guide action on these data to actually engage patients in care are sparse.¹¹⁶ Available interventions, such as case management and patient navigators, to help individuals who are suboptimally engaged in care or who have fallen out of care in the United States require intensive resources and may be difficult to reproduce in many parts of the world.

Community-based participatory research methods may be useful for addressing this specific health service challenge of test and treat. The National Institutes of Health defines community-based participatory research as

Scientific inquiry conducted in communities in which community members, persons affected by the condition or issue under study and other key stakeholders in the community’s health have the opportunity to be full participants in each phase of the work: conception, design, conduct, analysis, interpretation, conclusions, and communication of results.¹¹⁷

Community involvement in developing and studying behavioral and health system interventions to address social and structural barriers to retention and ART adherence may yield better solutions to these persistent challenges by accounting for the local cultural and social contexts in resource-limited countries.

Concerns about health care systems or health care workforce capacity to successfully absorb increased patient volumes and provide high-quality, guideline-based care were surprisingly infrequently noted, despite their importance to the success of test-and-treat programs. Implementation issues related to systems and workforce capacity may be best addressed through the use of health services and implementation science research methodologies.^118,119 Two Africa-based studies, Population Effect of ART Therapy to Reduce HIV Transmission and Treatment as Prevention, and 1 US-based study, Feasibility of an Enhanced Test, Link to Care, Plus Treat Approach for HIV Prevention in US, are currently in the field and will assess feasibility, costs, and best approaches for universal testing and treatment in communities.^{24,110,120–122} Aside from these studies, more location-specific implementation questions will likely remain as programs are rolled out. Rapid cycle quality improvement approaches may be particularly effective, as they provide timely and locally applicable data to track performance, highlight areas for improvement, and measure the impact of changes in program design.¹²³ Investment in and integration of performance measurement systems in the care delivery system from the beginning will be the best way to ensure that test-and-treat programs have reliable and inexpensive access to data to ensure patient safety and maximal program effectiveness.

More attention should also be paid to developing integrated and comprehensive care delivery models in resource-limited settings to replace fragmented health systems designed for specific diseases. Innovative methods, such as community mobilization, locating HIV care outside standard health care settings, and task shifting to lay workers, may also be more effective and successful models of health care delivery. Project Accept, a cluster-randomized, controlled trial of community-based voluntary counseling and testing in which community mobilization and community-based service approaches were compared with standard voluntary counseling and testing at clinical locations, demonstrated substantially greater patient testing rates and HIV case detection with community involvement.¹²⁴

Lastly, sustainable funding to scale up HIV care systems and ensure lifelong treatment remains an enormous challenge at this time of global economic uncertainty. The Joint United Nations Programme on HIV/AIDS estimated that to achieve universal access to appropriate HIV services worldwide in accordance with current treatment guidelines, $42.2 billion—a 4-fold increase in investment from 2007 levels—would be required.¹ Unfortunately, with funding in 2009 plateauing at $15.9 billion, only 36% of the 15 million people in need in low- and middle-income countries had received treatment by the beginning of 2010.^28,125,126 Cost estimates for a test-and-treat strategy would certainly exceed the estimated resources needed for guideline-based therapy, at least until HIV incidence dramatically declines. In addition, costs associated with programs to improve retention and maintain the health care delivery infrastructure may not be appropriately factored into cost estimates.^46,127 It seems unlikely that test-and-treat can be financed because current funding levels cannot support adequate treatment of HIV-positive individuals meeting current treatment guidelines. However, showing that the test-and-treat strategy dramatically reduces HIV incidence in real-world settings may provide the strongest case yet for funding agencies and governments to invest the necessary substantial resources to eliminate the HIV epidemic.

Ethical Concerns

Test-and-treat raises prohibitive ethical concerns in terms of balancing public health ethics and principlism (autonomy, beneficence, nonmaleficence, and justice), distributive justice in resource-limited settings, and concern for patient coercion. Because of existing clinical uncertainties and health service challenges, the ethical justification for the test-and-treat strategy is grounded in public health ethics and utilitarianism. This is a shift from the patient-centered principlism on which HIV care and treatment has traditionally been based.^15,57,128 Public health ethics allows the use of restrictions, mandates, and quarantines when the risk to the many outweighs the personal liberties of the few. It remains unclear, however, whether the public health benefits of test-and-treat sufficiently outweigh the potential risks to the individual, particularly risks related to early initiation of ART. If there is increased risk of drug toxicity and eventual drug resistance for individuals starting ART early, the argument in favor of utilitarianism over principlism becomes more difficult to justify.⁵² If, as is anticipated, more evidence emerges demonstrating a safety and survival benefit to the individual from treatment at earlier stages of disease, HIV test-and-treat will no longer require a careful assessment of this ethical balancing act and may be ethically practiced with respect to both the individual and society.

In the absence of definitive data on the individual-level clinical benefits and risks and the public health benefit of reduced HIV incidence, it is difficult to ethically justify widespread implementation of test-and-treat. Even if the clinical and public health benefits are shown to outweigh the risks in research settings, effective approaches to the health service challenges related to widespread implementation demand attention. From an ethical perspective, without health systems capable of delivering test-and-treat effectively, the favorable benefit–risk ratio realized in research studies may not be achieved. Considering the enormous potential benefits of test-and-treat, it could be argued that carefully controlled implementation trials that test the effectiveness of the strategy are an ethical imperative.

Another significant ethical complexity relates to distributive justice, or the equitable allocation of resources.¹⁷ As scarce resources are employed for test-and-treat, it is conceivable that programs may provide ART to asymptomatic individuals in 1 setting, whereas elsewhere vast numbers of individuals who meet current World Health Organization guidelines for therapy would not receive treatment.⁷¹ Redistributing these scare resources also has the potential for the test-and-treat strategy to divert resources away from other forms of HIV prevention and other diseases and conditions.⁶⁷

The potential for patient coercion in implementing test-and-treat also requires attention. Providers and health system staff may implicitly or explicitly feel pressured to ensure that they test or start as many patients as they can on ART at the time of diagnosis. Although proper informed consent (discussion regarding diagnosis, prognosis, risks, and benefits of early vs delayed treatment) as well as safeguards against the social stigma of HIV are still possible in such encounters, these discussions and safeguards may be inadvertently compromised by test-and-treat. This is especially true when the individual benefit of treatment may be perceived as relatively small. As pressure to perform mounts from external parties and funders, the potential for coercion will exist and is troublesome.^46,53,61 The ethical implementation of test-and-treat thus requires the systematic education of providers and improvement of systems to ensure that undue pressure on providers is minimized to decrease the potential for patient coercion.

The Population Effect of ART to Reduce HIV Transmission study, which uses mixed methods to assess community engagement and acceptability and human rights concerns to inform the design of a test-and-treat trial in 2 communities in Zambia and Uganda, will help address these 3 ethical issues.^23,120 The study will include qualitative research on trust, barriers, and experiences in service delivery; an assessment of 5 components related to human rights and ethics; and engagement with African partners to identify study sites, all while highlighting local issues that are key to implementing the test-and-treat strategy.^23,120

Outside the context of the Population Effect of ART to Reduce HIV Transmission study, the engagement of community members and persons living with HIV/AIDS will remain critical to the acceptance and success of test-and-treat implementation. Equitable partnerships that community-based participatory research of community stakeholders, persons living with HIV/AIDS, implementers, and, when applicable, researchers enable should be pursued to ease concerns about experimentation and coercion. By engaging in community-based consensus building, many of the health service challenges and ethical complexities of test-and-treat can be more optimally addressed in local epidemic contexts.⁶

Community mobilization is also considered a promising strategy to address stigma related to HIV/AIDS and other social vulnerabilities affecting access to and use of HIV care.^32,129,130 This is especially true in resource-poor areas to ensure that the benefits of current research endeavors being conducted there are not simply transplanted to resource-rich areas but that researchers strive to implement the results of their work in the communities supporting the research.¹³¹ Empowering local organizations through community partnership can ensure that the public health agenda and need for knowledge generation is balanced by the community’s perception of mutual benefit.¹³²

Conclusions

Innovative modeling and recent empirical evidence suggest that the test-and-treat strategy is an important and unparalleled opportunity to address the HIV epidemic. A great deal of work related to numerous clinical uncertainties, health service challenges, and ethical complexities remains to be done. Until this work is done, implementation efforts should be focused on achieving universal testing and treatment according to current World Health Organization guidelines for the initiation of ART. A strategic and thoughtful approach to research, implementation, and community engagement to achieve guideline-based treatment will necessarily require addressing and finding solutions for many outstanding clinical, health service, and ethical concerns, bringing us closer to making the promise of test-and-treat a reality.