Exciting new research has the potential to finally bring together two often-antagonistic branches of HIV/AIDS activities, treatment and prevention. The recently published results from the HIV Prevention Trials Network 052 study (HPTN 052) demonstrate the power of early antiretroviral treatment (ART) for almost completely preventing onward sexual HIV transmission in the clinical trial setting. This study offered proof of the concept that reduction of viral load through treatment could prevent HIV transmission, a concept that has served as the foundation for multiple modeling studies on treatment-as-prevention and one which was already held to be true by many. The data are incontrovertible, and although they resolve the question of whether this approach can prevent HIV transmission, they also lead to a more fully informed discussion of how ART might actually be used to prevent transmission in communities. The articles included in this special section consider many of the points in such a discussion.
For example, many programmatic considerations must be addressed in order to scale up the impressive results from HPTN 052. How can this effect be replicated in a general population using routine public health or clinical care services? For such community-wide efforts, we will need efficacious, well tolerated ART regimens that are as simple as possible to take, have a high barrier to resistance, and preserve future options for therapy. What research agenda will be needed to deliver such a regimen quickly and at a price that can be sustained by the public health systems of those countries in most need of treatment-based prevention? Many modeling exercises have assumed that treatment would ideally be delivered to all or almost all HIV-infected individuals, especially those who have recently been infected. However, it is widely acknowledged that programs this extensive do not exist even in the developed world and would most likely exceed program capabilities in resource-poor settings, at least in the near term. Could the cost-benefit of community-based interventions be improved, for example, by concentrating on the subpopulations most likely to transmit the virus?
The first section of this issue offers an historical perspective on the conduct of HPTN 052 and its research and policy implications. Cohen et al. provide insight into ethical and logistic considerations during trial planning and how the study adapted to the changing treatment landscape over the course of its conduct. The results of this study clearly establish treatment-as-prevention as an integral part of combination prevention interventions and underscore the need for robust HIV testing with seamless linkages to treatment. The resultant research agenda will need to include both basic and applied research to improve and increase HIV testing, strengthen linkages to care, and increase adherence for those receiving ART. The policy implications are unclear owing to our incomplete knowledge of a number of factors, such as the magnitude of effects expected in different communities and the durability of these effects. What appears to be clear is that even under the current testing and treatment paradigms, ‘serious concerns have arisen regarding the (United States) healthcare system's ability to meet the growing demand for HIV testing, access to medications, and linkages to sustained care’ (Institute of Medicine. HIV screening and access to care: healthcare system capacity for increased HIV testing and provision of care. Washington, DC: 2011). Policy makers will need to find ways to address these gaps in the HIV prevention, treatment and care continua for the potential benefit of treatment-as-prevention interventions to be realized at the community level.
The second section deals with practical considerations. The need to treat all HIV-infected individuals can appear daunting and is currently beyond the reach of many programs. Novitsky and Essex explore the possibility of focusing on individuals with recent infection who have high viral load for extended periods after seroconversion [most points they raise also hold true for individuals with the most recent (acute) infections]. Individuals with high viremia have the greatest potential to transmit. Those with extended high viremia may represent the main source of new transmission cases in communities; they may also be at the highest risk for disease progression. Advances in HIV diagnostics may facilitate detection of individuals with acute or recent infection as new technologies can detect HIV RNA and viral antigens in HIV-infected individuals prior to seroconversion; albeit, such technologies rely on successful routine detection programs. Early detection, in turn, raises issues of acceptability, adherence, clinical outcome, risk compensation, and resistance, as well as the risk-benefit balance of early treatment for the patient. Although concerns about cumulative toxicity have been raised, this potential drawback should diminish over time as newer ART regimens become safer, better tolerated, and simpler; accumulating data support the personal benefit of early ART initiation.
The final three articles examine the feasibility of scaling up treatment-as-prevention interventions in large populations, examining such questions as whom to prioritize for maximum equity, fairness, and impact. Two articles describe markedly different situations: the generalized epidemic among heterosexuals in sub-Saharan Africa and the concentrated epidemics among injection drug users (IDUs) in North America. Studies of HIV testing, linkage to care, and adherence in Africa have been conducted in settings wherein individuals with early HIV infection were not eligible for treatment; thus, the implications from these studies on treatment-as-prevention interventions remain unclear. Perhaps, more optimistic results are seen in North American population-level studies of community viral load, which should be directly affected by treatment-as-prevention interventions; nonetheless, these programs will need to mitigate risk and promote safe behavior. For IDU, as for other populations, it will be important to remove barriers to access to care and adequate adherence, such as criminalization and stigma.
The articles in this section help clarify issues but don’t necessarily resolve all of them. First, how will treatment-for-prevention programs affect ‘treatment-for-treatment’ programs? For example, although treatment-as-prevention could be key in achieving the goals of the US National HIV/AIDS Strategy (reducing HIV incidence, improving access to care, and reduction in HIV-associated health disparities), it is not clear what changes will be needed in the US healthcare system to implement such a program. Furthermore, it is unclear how treatment-as-prevention programs can be brought to scale in resource-poor countries that cannot even treat all those who meet current treatment guidelines. What resources can be brought to bear in these settings to allow expansion of testing and treatment to include all HIV-infected individuals or to target for inclusion those with acute or recent infection or high viral loads? Moreover, how will treatment-as-prevention be integrated into other prevention programs and combined with other strategies (including circumcision, microbicides, and PrEP)? How will the individual components be prioritized? The answers to many of these questions elude us at present. The results from ongoing and newly initiated studies and policy analyses will be needed for opening a dialogue on how best to optimally incorporate this promising new prevention strategy.
There are no conflicts of interest.
Conflicts of interest