Transmissible disease of the immune system caused by HIV. AIDS is the last stage of HIV infection, during which time the individual develops frequently fatal infections and cancers, including Pneumocystis carinii pneumonia, cytomegalovirus (CMV), lymphoma, and Kaposi sarcoma. The first AIDS cases were identified in 1981, HIV was isolated in 1983, and blood tests were developed by 1985. According to the UN's 2004 report on AIDS, some 38 million people are living with HIV, approximately 5 million people become infected annually, and about 3 million people die each year from AIDS. Some 20 million people have died of the disease since 1981. Sub-Saharan Africa accounts for some 70 percent of all HIV infections. Rates of infection are lower in other parts of the world, but the epidemic is spreading rapidly in eastern Europe, India, South and Southeast Asia, Latin America, and the Caribbean.
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The Division supports a large portfolio of investigator-initiated grants that are pursuing research focused on, but not limited to, the following areas: mechanisms of viral entry and infection, including the role of co-receptors and other cellular accessory molecules; the structure, function, and mechanism of action of viral genes and proteins; development of in vitro and ex vivo assays to monitor virus growth and immune responses against HIV, and animal models for research on the regulation and function of viral proteins and genetic regulatory sequences; the immunological and virological events controlling primary infection; factors effecting latent reservoirs of HIV; and host factors that modulate viral infection and/or disease progression.
The Division's basic research efforts have yielded significant scientific information about HIV. For example, in recent years, DAIDS-funded investigators have identified new structures for viral components of HIV, additional chemokine co-receptors, and the existence of multiple, persistent HIV reservoirs even with the use of highly active antiretroviral therapy (HAART). Despite these advances, questions still remain about the molecular interactions involved in the regulation of HIV expression and replication. More information is also needed about how the virus evades the immune system in order to identify additional targets against which therapeutic interventions and vaccines can be directed.
In order to foster drug development of new HIV therapies, DAIDS supports research on potential new cellular and viral therapeutic targets and new approaches to validate targets; molecules that could effectively block HIV replication; improved formulation of existing agents; approaches to restore the immune system of HIV-infected individuals; molecular and genetic approaches to protect susceptible, uninfected cells; combination regimens that impede the emergence of viral resistance; and assays to measure restored immunity of HIV-infected individuals.
The evaluation of new drugs and therapeutic agents in people is another critical aspect of therapeutic research. These clinical studies define which new agents are effective against HIV and its associated OIs and also clarify how best to use these drugs.
DAIDS-sponsored therapeutics research has already had a dramatic impact on our understanding of the pathogenesis and clinical management of HIV infection over the last decade. Studies conducted by DAIDS-funded clinical trials research networks have:
More recent studies have shown that highly active antiretroviral therapy-regimens including reverse transcriptase and potent protease inhibitors-are capable of suppressing HIV viral load to undetectable levels in many infected individuals and partially restoring immune function. Such regimens have had a dramatic impact on HIV mortality in this country.
Nonetheless, treatment failures occur as a result of the development of resistance and/or noncompliance with complicated and often toxic regimens. Moreover, damage to the immune system is incompletely reversed. Thus, there is an ongoing, urgent need for new therapeutic agents and new ways to boost the immunity and rebuild and replace immunity lost to HIV infection. In addition, strategies to address critical questions regarding the long-term effects of antiretroviral therapy and the best approaches to medical management are being developed.
Through a balanced HIV program that integrates both basic research and empiric testing of candidate vaccines, NIAID supports a broad spectrum of research and development on HIV/AIDS vaccines. Preclinical vaccine research and development examines new vaccine concepts or approaches and new ways to deliver HIV antigens to people and to safely induce a potent anti-HIV immune response. Studies in animal models are aimed at defining how a vaccine could protect the host. For now, clinical evaluations in humans provide the only way of determining whether a vaccine candidate could trigger a safe and effective anti-HIV response in people.
NIAID also supports comprehensive research on other biomedical/behavioral prevention approaches, including drugs and/or vaccines that prevent mother to infant HIV transmission, including during breastfeeding, microbicides for preventing sexual transmission of HIV, interventions that reduce behaviors that expose people to HIV, programs to reduce intravenous drug abuse, measures to control other sexually transmitted diseases (STDs), and antiretroviral therapies that may reduce the spread of HIV from infected people to their partners. This comprehensive vaccine and prevention program has led to a number of significant scientific advances in vaccine and prevention research. In the past, NIAID supported researchers have improved antigenicity through modifications to the envelope protein, elucidated the envelope structure of HIV, advanced our understanding of the role of cellular responses in controlling HIV, developed improved assays for measuring cytotoxic T lymphocytes (CTLs), developed new and better animal models for testing candidate vaccines, and evaluated promising candidates in animal and clinical studies.
In order to accelerate identification of effective vaccine candidates, future studies will need to address the significance of latently infected resting T cells, immune responses induced by current vaccine candidates, and the impact of HIV and HLA diversity. In addition, the relevance of SIV/SHIV models and the utility of novel vaccine designs must be explored. With regard to prevention research, new microbicides need to be developed and tested and new regimens for preventing maternal-infant transmission during breastfeeding, which are effective and practical for developing countries, need to be explored. Lastly, because the majority of new infections are occurring in the developing world, NIAID's vaccine and prevention research activities are conducted on a global scale. These research programs are designed to define global research priorities, ensure the clinical relevance of future vaccine and prevention strategies to human populations most in need, strengthen collaborations with local investigators worldwide, and support training and infrastructure development in developing countries.
The coordination of this complex program of AIDS research is an important function of DAIDS. By surveying developments in key scientific areas, DAIDS assesses ongoing needs in biomedical research as well as requirements for outreach activities and for training scientific investigators. As part of this process, DAIDS works with advisory groups and community and health professional organizations, evaluating and redirecting program emphases to respond to changing research needs.