Develop and assess intervention strategies to reduce or prevent HIV transmission in both domestic and international settings.

1. Develop and maintain the infrastructures to define populations in the United States and throughout the world with incidence and prevalence suitable for vaccine and other intervention trials (e.g. microbicides, barriers, treatment, behavioral) for preventing HIV transmission.
2. Support development and evaluation of improved, acceptable, effective physical and chemical barrier methods and conduct research on existing barrier methods to prevent sexual transmission of HIV and STDs.
3. Develop strategies and conduct studies to evaluate vaccines, drugs, and other interventions such as caesarean sections, vaginal cleansing, breast-feeding practices, nutritional interventions, and other approaches that prevent perinatal transmission.
4. Develop and assess the efficacy of strategies that may decrease transmission of HIV among drug users.
5. Develop and evaluate biological and behavioral interventions to control STDs as co-factors in HIV transmission.
6. Develop strategies that enhance safe sex behaviors and provide information on safe and effective contraceptive choices for at-risk women.
7. Develop methods to prevent infection in hard-to-reach gay male populations such as young, substance-using, and minority gay and bisexual men.
8. Develop methods of accessing hard-to-reach populations to identify factors that contribute to recruitment (and retention) into prevention and intervention activities.
9. Evaluate access to, acceptability of, and compliance with interventions such as AZT for perinatal transmission, condoms, and virucides.
10. Evaluate improved procedures for screening, monitoring, and inactivating HIV and other retroviruses in the blood supply; and develop and evaluate alternatives to blood transfusion.
11. Assess the impact of drug and alcohol abuse and mental health impairment on efficacy of behavior modification interventions directed at sexual transmission.
12. Develop effective drug treatment strategies for addiction, particularly focused on heroin and cocaine use.

The development of biologically based interventions to interrupt transmission is an essential component of a comprehensive HIV prevention strategy that also includes behavioral intervention strategies as well as efforts to develop a vaccine(s). International studies should be supported with the goal of developing prevention strategies that can be used to reduce HIV transmission in the United States. Research is ongoing in these areas. Epidemiologic studies, including vaccine preparedness research, provide opportunities for intervention research in defined cohorts of well-characterized populations. Strategies that employ therapies, devices, and other approaches, such as needle/syringe exchange programs using HIV seroconversion end points, are useful approaches for providing epidemiologic causation and evaluating effectiveness in preventing or reducing HIV transmission.

In addition, despite the fact that the blood supply in the United States is safer than it has ever been, it is important to develop even better methods for maintaining and improving its safety.

Characterize the risk factors and mechanisms of HIV transmission in both domestic and international populations, with the goal of preventing transmission.

1. Evaluate HIV transmission in relationship to: viral factors such as virus load in the blood and at mucosal sites, characteristics of HIV (genotype and phenotype), and pre-existing infection with other agents; host factors such as contraceptives, pregnancy, menstrual cycle, substance abuse, and nutritional, immunologic and genetic determinants; local factors including intercurrent STDs, exogenous irritants, oral and anogenital inflammation, mucosal immunity, circumcision and cervical ecotopy.
2. Further define the timing and mechanisms and risk factors in perinatal transmission, including breast-feeding.
3. Study mechanisms of resistance to HIV infection in persons who remain uninfected despite perinatal, sexual or parenteral exposure.
4. Define the determinants of high-risk behavior for transmission through drug use and sexual practices.
5. Characterize the dynamics of HIV transmission in epidemiologic studies of at-risk groups, including evaluation of sexual and drug-using networks, social and geographic mixing patterns, and turnover rates of at-risk populations.
6. Characterize the transmission and host immune responses of related retroviruses.

Understanding the role of risk factors and mechanisms of HIV transmission is critical to the development of biologically and behaviorally based strategies to interrupt transmission of HIV. Epidemiologic studies provide important biological and behavioral information including the role of co-factors that may reduce or enhance transmissibility.

Elucidate the progression of HIV infection, from its earliest stages through long-term sequelae, with the goal of understanding, preventing, and treating those factors.

1. Use epidemiologic studies to identify pathogenic mechanisms and co-factors for disease progression and disease-specific outcomes in well-defined subsets of individuals, individuals, including those with different rates of progression.
2. Conduct epidemiologic studies to understand the initiation and progression of early HIV infection, according to route of exposure, viral dose, viral genotype and phenotype, and host response, and how these early events influence disease progression. Use epidemiologic studies to investigate the influence of viral genotype and phenotype on transmission efficacy and disease progression.
3. Use epidemiologic studies to evaluate the extent of dissemination of drug-resistant strains of HIV and its impact on pathogenesis.
4. Study the natural history of related retroviruses to elucidate retroviral pathogenesis.
5. Elucidate the mechanisms of HIV-associated carcinogenesis to improve strategies for early diagnosis and intervention.
6. Study HIV-infected children to determine:
   1. mechanisms that contribute to impaired growth and neurodevelopment;
   2. impact on childhood infectious diseases and the safety and efficacy of immunization;
   3. impact on childhood psychosocial development, and
   4. childhood-specific complications.
7. Evaluate the interaction of hormonal factors (including pregnancy, contraceptives, and hormonal replacement therapy) and HIV disease progression.
8. Study the progression of HIV-related disease in adolescents who have acquired their diseases as a result of drug use and/or sexual activity.
9. Study the natural history of HIV infection in the nervous system, including cognitive impairment, dementia, and neuropathy.
10. Describe the full spectrum of HIV-related diseases in HIV-infected populations.
11. Maintain and effectively utilize national specimen repositories for HIV-related studies.

Epidemiologic studies provide a critical knowledge and resource base for more basic investigations of HIV pathogenesis. A better understanding of the diversity of HIV-related disease outcomes, co-factors for progression, and predictors of disease progression will be important in furthering attempts to develop HIV vaccines and more effective therapeutic interventions against HIV and its sequelae.

Undertake epidemiologic research to reduce or prevent the occurrence of opportunistic illness in HIV-infected persons.

1. Study the impact of HIV infection on the emergence of new human pathogens and the impact of HIV infection on the reemergence of infectious diseases domestically and internationally.
2. Identify risk factors for the acquisition of opportunistic pathogens.
3. Study the determinants of the continuing occurrence of preventable opportunistic illnesses.
4. Study the role of transmissible and other preventable exposures in the etiology of AIDS-associated cancers and other outcomes.

Most morbidity and mortality in HIV-infected persons result from the occurrence of opportunistic illnesses, including both infections and malignancies. Strategies to prevent these illnesses include prevention of exposure to the etiologic agents, prevention of disease in those who are exposed, and prevention of disease recurrence. Additional epidemiologic data are needed to design more effective strategies to prevent the occurrence of these opportunistic illnesses.

Develop and evaluate new laboratory assays, behavioral methods, and statistical techniques for epidemiologic studies.

1. Promote development and evaluation of virologic and immunologic assays to elucidate mechanisms of HIV transmission and disease.
2. Develop new survey and interview techniques to better measure HIV risk behaviors.
3. Develop new biostatistical techniques, including mathematical models, to better characterize transmission dynamics and disease progression.
4. Develop innovative approaches for record linkages to study HIV-associated diseases and mortality.
5. Characterize the epidemiologic features of emerging HIV variants, including drug-resistant strains, diverse genotypes, and newly recognized geographic distribution.

Epidemiologically defined populations contain well-characterized cohorts that can provide insights into HIV transmission, including resistance and susceptibility to infection and infectiousness, and into progression of HIV-related disease, from early infection through long-term sequelae, including cancer and neurocognitive impairment. The application of innovative biomedical research and behavioral strategies to such populations will greatly increase understanding at the biological level and will help to identify strategies for prevention of transmission and for clinical management of patients.

All populations.

Researchers, clinicians, community and patient representatives, and NIH-affiliated advisory councils and committees.