AIDS and Immunosuppression Program
Center for Integrative Biology and Infectious Diseases
OBJECTIVE
The primary goal of this initiative is to drive interdisciplinary research to study the oral manifestations and complications associated with HIV/AIDS-related immunosuppression in vulnerable populations, including children and adolescents. We propose to solicit integrated projects that comprehensively address the existing gaps in our knowledge of the epidemiology, prevention and pathogenesis of the oral complications of HIV disease and to promote interventions that could reduce the burden of disease among disproportionately affected racial and ethnic minority communities. Regardless of the theme, projects in each multidisciplinary program will be expected to be synergistic and to utilize cutting-edge approaches such as genomics, proteomics, molecular imaging and other emerging technologies to achieve their goals. Applicants will be encouraged to include pediatric/adolescent populations in their research. In addition, it is expected that these projects will provide interdisciplinary career development opportunities for investigators new to the field of oral AIDS.
BACKGROUND
In the past two decades significant progress has been achieved in HIV/AIDS research that has led to better treatments, longer life spans and better quality of life. The pattern of HIV/AIDS has now evolved to become a chronic infectious disease. With the increase in the life expectancy of patients with HIV/AIDS attention to patient, family and provider awareness of the oral manifestations of HIV/AIDS and the complications that may be associated with the chronic infection and /or treatment is warranted, particularly among children and adolescents. Vulnerable populations at risk of acquiring the disease include intravenous drug abusers, and racial and ethnic minorities. While African Americans make up approximately 13% of the population in the US, they account for approximately half of the new HIV/AIDS new diagnoses. Other vulnerable populations that merit attention are children and adolescents. Half of the new HIV infections in the US annually are among young people 13 to 24 years of age. Oral manifestations of HIV infection occur in 30 to 80 percent of the affected patient population. Children and adolescents of ethnic minorities continue to bear a disproportionate burden of the epidemic.
Oral lesions are among the early signs of HIV infection and can predict the progression to AIDS. Oral lesions commonly associated with HIV infection include oral candidiasis, herpes simplex infection, oral Kaposi’s sarcoma (KS), parotid enlargement, periodontal and gingival diseases and recurrent mucosal ulceration among others. Children share similar oral manifestations to adults but with a lower frequency of oral KS and more parotid enlargement. In addition HIV infected children develop dental caries at a higher rate than the general population, and exhibit delayed dental eruption and retention of primary teeth. HIV salivary gland disease (SGD) is also frequently observed in children; it is characterized by enlargement of the major salivary glands and xerostomia in the absence of xerogenic medications/agents. The decreased salivary flow associated with SGD predisposes these patients to rampant dental caries.
Adolescent populations are one of the more challenging age groups to study and treat due to their particular vulnerability to HIV infection and sexually transmitted diseases. The management of this age group requires an understanding of the behavioral and psychological issues pertaining to their development. The majority of HIV seropositive adolescents acquire their infection during the adolescent period. However with the improvement in antiretroviral therapy strategies a growing number of perinatally infected youth are now living to see the teenage and adult years. The fact that adolescents and children are living longer necessitates special considerations to their quality of life to ensure healthy dentition, adequate nutrition and fulfillment of the psychosocial aspects of their development. All of this can impact the outcome of the disease and adherence to therapy.
Our understanding of the pathogenesis of HIV infection and subsequent associated oral complications is incomplete. This area of research includes oral disorders caused by pathogens such as EBV, HPV, CMV, HHV-8, HSV, bacteria and Candida. The relative ability of the oral cavity to resist HIV infection and replication while providing a safe haven for other pathogens provides a unique opportunity to dissect the differential patterns of host defenses. This can shed light on the mechanisms utilized by oral pathogens to evade the immune response and the mechanisms involved in reactivation of latent oral viral pathogens to cause disease. This knowledge has the potential for development of novel more effective strategies for prevention and treatment of such complications.
Examples of research that will be supported under this initiative include but are not limited to systematic research aimed at addressing the burden and determinants of oral disorders associated with HIV disease in children/adolescents in resource limited populations; strategies to resolve the barriers that prevent adolescents from getting tested for HIV and accessing oral/dental care and preventive services; studies on salivary gland disorders in HIV infection, including basic research on etiology, pathogenesis, epidemiology and prevention; and oral mucosal immunity to microbial pathogens associated with oral complications of AIDS.