Since the 1980s when the HIV/AIDS epidemic was first recognized, NIAID-supported clinical research has helped to save millions of lives and played a key role in defining the standard of care for treating HIV infection. This blog post describes what we are seeking for the next wave of HIV/AIDS therapeutic approaches. Specifically, we have identified the following three research priorities: 1) finding a cure for HIV-infected individuals; 2) developing therapeutic strategies for preventing and treating tuberculosis (TB) and hepatitis C in HIV-infected individuals and individuals at high risk for co- infection; and 3) addressing the long-term consequences of treatment of HIV infection.
A cure for HIV/AIDS would have a significant impact on the global burden of HIV/AIDS by reducing HIV prevalence and providing increased hope for controlling and ultimately ending the pandemic. Current antiretroviral therapy (ART) used to treat HIV infection suppresses the virus’ ability to replicate but does not eliminate the hiding spots in the body where the virus lays dormant (called “reservoirs”). We define a “cure” for HIV-infected people as permanent remission of disease in the absence of therapy. Currently, we are investigating two distinct approaches toward this type of cure: identifying each of the HIV reservoirs and finding ways to eliminate them; and maintaining and/or boosting the immune system, so that it can control HIV replication on its own when ART is discontinued. Evaluating both approaches will require innovative and rigorous clinical research. Additionally, specialized laboratories will be needed to measure a variety of parameters, such as reservoir size, the low levels of virus that continue to persist, and anti-HIV immunity. These clinical activities will need to be closely linked with existing efforts to discover and develop strategies for a cure.
Until there is a cure for HIV infection it is critical that we continue to develop strategies for preventing, diagnosing and treating infectious diseases commonly associated with HIV, such as TB, which is the leading cause of death in persons with HIV/AIDS. Our TB research agenda will include the development of new regimens for prevention and treatment. The goal is to have treatment regimens that are effective, well-tolerated and shorter in duration, that do not interfere with the effectiveness of ART, and that target drug-sensitive and resistant TB, including extensively drug resistant TB. Discovery and careful assessment of improved diagnostics, drug-sensitivity testing, and biomarkers for predicting disease progression and therapeutic responses are priorities since TB manifests itself in different ways in HIV/AIDS patients and is much more difficult to diagnose than in people without HIV infection.
Co-infection with HIV and hepatitis C virus is another area of major concern. Current therapies for hepatitis C are often poorly tolerated and are not effective against all subtypes of the virus. At least seven new treatments are in development for hepatitis C infection, and we hope that some of these will lead to safer and more effective regimens for people infected with both HIV and hepatitis C virus. In addition to new treatments, there is a great need for new hepatitis C diagnostic tools, including detection of proteins in blood that predict treatment success or failure.
- Are the three priority areas that we have identified for HIV/AIDS therapeutics research the appropriate priorities?
- What is the best way to link the discovery and clinical evaluation of possible cures for HIV/AIDS?
- Are we defining an HIV/AIDS “cure” appropriately?
- On what areas of TB and hepatitis C clinical research should NIAID focus? Are there other infectious agents that deserve priority efforts?
- What are the most important non-infectious co-morbidities associated with HIV infection that NIAID should address in its research agenda?
- Can earlier initiation of antiretroviral therapy for HIV infection prevent some of the premature aging and other co-morbidities associated with treated HIV disease, or are other targeted therapeutic approaches required?
- What is the best approach for advancing HIV, TB, and hepatitis C biomarker research?
For both TB and hepatitis C, significant research efforts are supported by several public and private sector funders, including other divisions within NIAID. These areas of the therapeutics agenda need to be coordinated with existing research efforts to facilitate more efficient clinical research planning and highly productive collaborations.
Effective therapy for HIV infection has been available for about 15 years. During this time, antiretroviral drugs have become safer and easier to take. However, we still do not fully understand the consequences of long-term treatment of HIV infection, especially the mechanisms driving residual inflammation. A major concern is the increased rates of certain conditions experienced by HIV-infected individuals who have been infected for long periods of time, even those whose viral load has been adequately suppressed with ARV therapy. These include the onset of early aging characteristics, cardiovascular disease, insulin resistance, non-AIDS-associated cancers and kidney disease. Basic and clinical research are needed to define the underlying mechanisms of these conditions and develop therapeutic strategies to target these mechanisms. The key to developing novel therapeutic strategies will involve both the investigation of biomarkers and the evaluation of novel HIV therapies.
We welcome your thoughts and feedback on these issues. It has been interesting to see the responses to our two previous blog postings, and I hope you will continue to comment.
In the next blog posting, we will examine the direction of NIAID’s HIV vaccine clinical research priorities.