HIV-AIDS: much accomplished, much to do.

As a result of decades of research-driven breakthroughs in basic and clinical science and recent advances in the broad-scale implementation of interventions for the prevention and treatment of infection with HIV, a turning point has been reached in the global HIV-AIDS pandemic. To end the pandemic and achieve the goal of an AIDS-free generation, researchers and clinicians must follow the dual pathway of optimizing the implementation of existing prevention and treatment interventions and discovering with basic and clinical research new and effective tools in both of these arenas.

Ending AIDS as a public health threat by 2030: Time to reset targets for 2025.

Paul De Lay and co-authors introduce a Collection on the design of targets for ending the AIDS epidemic.

Thirty years of HIV and AIDS: future challenges and opportunities.

As the third decade since AIDS was first recognized comes to an end, extraordinary advances have occurred in the understanding, treatment, and prevention of HIV infection and AIDS. As a result of these successes, it is now time to focus on future challenges. Paramount among these is reaching the goal of truly controlling and ultimately ending the HIV and AIDS pandemic. To that end, AIDS researchers and public health personnel worldwide are aggressively pursuing 3 key areas of scientific research. Given the availability of highly effective therapeutic regimens for HIV infection, the first challenge is efficiently identifying a maximum number of HIV-infected persons through voluntary HIV testing and initiating antiretroviral therapy (ART). Second, scientists are trying to develop a cure for HIV infection, which would alleviate the need for lifelong ART. Finally, preventing new cases of HIV infection, which currently number approximately 2.6 million per year globally, is critical to any attempt to end this pandemic. This article addresses each of these challenges and provides directions for the future.

The case for an HIV cure and how to get there.

In light of the increasing global burden of new HIV infections, growing financial requirements, and shifting funding landscape, the global health community must accelerate the development and delivery of an HIV cure to complement existing prevention modalities. An effective curative intervention could prevent new infections, overcome the limitations of antiretroviral treatment, combat stigma and discrimination, and provide a sustainable financial solution for pandemic control. We propose steps to plan for an HIV cure now, including defining a target product profile and establishing the HIV Cure Africa Acceleration Partnership (HCAAP), a multidisciplinary public-private partnership that will catalyse and promote HIV cure research through diverse stakeholder engagement. HCAAP will convene stakeholders, including people living with HIV, at an early stage to accelerate the design, social acceptability, and rapid adoption of HIV-cure products.

Rethinking prevention of HIV type 1 infection.

Research on the prevention of human immunodeficiency virus (HIV)-1 infection is at a critical juncture. Major methodological challenges to performing prevention trials have emerged, and one after another promising biomedical interventions have failed to reduce the incidence of HIV-1 infection. Nevertheless, there is growing optimism that progress can be achieved in the near term. Mathematical modeling indicates that 2 new strategies, "test and treat" and preexposure prophylaxis, could have a major impact on the incidence of HIV-1 infection. Will our hopes be justified? We review the potential strengths and limitations of these antiretroviral "treatment as prevention" strategies and outline other new options for reducing the incidence of HIV-1 infection in the near term. By maximizing the potential of existing interventions, developing other effective strategies, and combining them in an optimal manner, we have the opportunity to bring the HIV-1 epidemic under control.

Role of Implementation Science: Linking Fundamental Discovery Science and Innovation Science to Ending the HIV Epidemic at the Community Level.

BACKGROUND: During the past 4 decades, substantial progress has been made in the development of strategies for HIV prevention, treatment, and care resulting from observational science, discovery and innovation science, and implementation science. Building on these fundamental discoveries, innovation science has led to novel, safe, and effective modalities for HIV treatment and prevention, including combination antiretroviral therapy and treatment as prevention and pre-exposure prophylaxis, respectively. SETTING: In the United States and globally, there remains a major challenge in the optimal implementation of the strategies that we already have in the areas of HIV prevention, diagnosis, treatment, and care. METHODS: Implementation science will be essential to the successful achievement of ending the global HIV epidemic by translating evidence-based interventions, resulting from discovery and innovation science, into real-world practice. Strategies are needed that integrate and implement the biomedical tools currently available within the social and structural contexts and across all stages of the HIV prevention and care continuum. Several of the latest methodologies and analytical approaches that are being actively pursued, as well as the research challenges and opportunities to conducting implementation science in the context of both the global and domestic responses to HIV, are the focus of this special supplement to the Journal of AIDS. CONCLUSIONS: Knowledge resulting from implementation science will be critical to define and refine the approaches to successfully bring HIV prevention and treatment interventions to scale and achieve the goal of ending the HIV epidemic in the United States and worldwide.

Preventing HIV transmission through antiretroviral treatment-mediated virologic suppression: aspects of an emerging scientific agenda.

PURPOSE OF REVIEW: This review describes important aspects of the research agenda that have emerged as a result of the recent findings of the HIV transmission study in sero-discordant couples conducted by the National Institute of Allergy and Infectious Disease (NIAID)-supported HIV Prevention Trials Network (HPTN) and referred to as HPTN 052. RECENT FINDINGS: The HPTN 052 study provided strong evidence that antiretroviral treatment (ART), given to HIV-infected partners with the purpose of achieving and maintaining full virologic suppression, could prevent linked HIV transmission in sero-discordant couples. These findings have implications in all future combination prevention strategies. SUMMARY: The HPTN 052 study demonstrated that sustained virus suppression, below detectable levels, can prevent HIV transmission in sero-discordant couples. As a result of this study, we have now identified ART as a key component for all combination prevention strategies. Additionally, this study demonstrates that HIV testing is the single door of entry for individualized HIV treatment and prevention. The challenge now is to create a robust, seamless linkage and retention system so that the vision of HIV treatment as prevention can be realized. Such a system will maximize both the treatment and the prevention benefits of ART. The research agenda outlined here describes the need to extend this finding to areas of implementation science, such as the development of simpler, easier to use point-of-care assays for virus load, and improved, better tolerated, more durable combinations and formulations of antiretroviral drugs.

HIV-1 vaccines and adaptive trial designs.

Developing a vaccine against the human immunodeficiency virus (HIV) poses an exceptional challenge. There are no documented cases of immune-mediated clearance of HIV from an infected individual, and no known correlates of immune protection. Although nonhuman primate models of lentivirus infection have provided valuable data about HIV pathogenesis, such models do not predict HIV vaccine efficacy in humans. The combined lack of a predictive animal model and undefined biomarkers of immune protection against HIV necessitate that vaccines to this pathogen be tested directly in clinical trials. Adaptive clinical trial designs can accelerate vaccine development by rapidly screening out poor vaccines while extending the evaluation of efficacious ones, improving the characterization of promising vaccine candidates and the identification of correlates of immune protection.

A way forward: the National HIV/AIDS Strategy and reducing HIV incidence in the United States.

In July 2010, the Obama Administration released a National HIV/AIDS Strategy for the United States to refocus national attention on responding to the domestic HIV epidemic. The goals of the strategy are to reduce HIV incidence; to increase access to care and optimize health outcomes among people living with HIV; and to reduce HIV-related disparities. The strategy identifies a small number of action steps that will align efforts across federal, state, local, and tribal levels of government, and maximally impact the domestic HIV epidemic. In this article, we outline key programmatic and research issues that must be addressed to accomplish the prevention goals of the National HIV/AIDS Strategy.

Planning for pre-exposure prophylaxis to prevent HIV transmission: challenges and opportunities.

There are currently several ongoing or planned trials evaluating the efficacy of pre-exposure prophylaxis (PrEP) as a preventative approach to reducing the transmission of HIV. PrEP may prove ineffective, demonstrate partial efficacy, or show high efficacy and have the potential to reduce HIV infection in a significant way. However, in addition to the trial results, it is important that issues related to delivery, implementation and further research are also discussed. As a part of the ongoing discussion, in June 2009, the Bill & Melinda Gates Foundation sponsored a Planning for PrEP conference with stakeholders to review expected trial results, outline responsible educational approaches, and develop potential delivery and implementation strategies. The conference reinforced the need for continued and sustained dialogue to identify where PrEP implementation may fit best within an integrated HIV prevention package. This paper identifies the key action points that emerged from the Planning for PrEP meeting.