Although in the current decade the HIV epidemic continues unabated, a notable success is that more than 20 different antiretroviral drugs are now available in many countries. When these antiretroviral drugs are used in combination, they improve health and prolong life in HIV-infected individuals and reduce the rates of transmission of the virus. Indeed, HIV-infected individuals who harbour a drug-susceptible viral strain, have access to antiretroviral drugs and are fully compliant with therapy can achieve and maintain complete, or near complete, viral suppression for years to decades. However, despite these successes, standard therapies do not fully restore health or a normal immune status in HIV-infected individuals, and patients still experience co-morbidities, such as increased cardiovascular disease, bone disorders and cognitive impairment1
. In addition, interruption of antiretroviral therapy almost invariably leads to the re-emergence of detectable viral replication and the progression of AIDS. Perhaps more importantly, only a minority of HIV-infected individuals globally have access to antiretroviral therapy.
The cost of antiretroviral therapy has decreased substantially in recent years, and the availability of these drugs in resource-poor settings has steadily increased. However, the cost associated with delivering antiretroviral drugs to the 33 million people who are now living with HIV is overwhelming many organizations and public health systems. It is estimated that for every HIV-infected person who starts antiretroviral therapy, two individuals are newly infected with HIV; this is clearly unsustainable2
. The continued presence on a global level of a large number of untreated HIV-infected individuals — who are the main source of ongoing HIV transmission3
— means that the infected population is likely to grow. Given these well-recognized issues, there is a growing interest in developing curative strategies to tackle HIV4-6
. Theoretically, a safe, affordable and scalable cure could address both the individual and public health limitations that are associated with lifelong antiretroviral therapy.
The International AIDS Society (IAS) convened a team of more than 40 scientists who are active in the field of HIV research. We have met frequently over the past 2 years. Throughout this process, the IAS has engaged with a broad range of stakeholders from around the world and has exhaustively solicited advice on the steps that should be taken to develop a cure for HIV infection. These efforts include the creation of a stakeholders’ advisory board, and online and in-person discussions with hundreds of community activists, representatives from pharmaceutical and biotechnology industries, funding and regulatory agencies, and key HIV and non-HIV researchers from across the world.
In this Opinion article, we provide a concise, multidisciplinary plan that identifies a set of key scientific priorities that should bring us measurably closer to our vision of developing a cure for HIV infection (BOX 2
). These priorities span the areas of basic, translational and clinical investigation. Two broadly defined approaches for curing HIV infection were considered by the group: first, the elimination of all HIV-infected cells (a sterilizing cure); and, second, the generation of effective host immunity to HIV that would result in lifelong control of the virus in the absence of therapy, despite not achieving the complete eradication of HIV (a functional cure). Here, we describe how the priorities identified by the IAS can allow us to achieve a sterilizing or functional cure for HIV.
Box 2. Seven key scientific priorities for HIV cure research
- Determine the cellular and viral mechanisms that maintain HIV persistence during prolonged antiretroviral therapy and in rare natural controllers. This includes defining the role of mechanisms that contribute to the establishment and maintenance of latent infection, as well as defining the role of ongoing viral replication and/or homeostatic proliferation.
- Determine the tissue and cellular sources of persistent simian immunodeficiency virus (SIV) or HIV in animal models and in individuals on long-term antiretroviral therapy.
- Determine the origins of immune activation and inflammation in the presence of antiretroviral therapy and their consequences for HIV or SIV persistence.
- Determine host mechanisms that control HIV replication in the absence of therapy.
- Study, compare and validate assays to measure persistent HIV infection and to detect latently infected cells.
- Develop and test therapeutic agents or immunological strategies to safely eliminate latent infection in animal models and in individuals on antiretroviral therapy. This includes strategies aimed at reversing latency, as well as strategies aimed at clearing latently infected cells.
- Develop and test strategies to enhance the capacity of the host immune response to control active viral replication.