Opportunistic Infections Research - National Institute of Allergy and Infectious Diseases
AIDS-RELATED HERPES SIMPLEX VIRUS INFECTION
Acquired immunodeficiency syndrome (AIDS), a life-threatening disease of the immune system, has become a worldwide epidemic since 1981,the year it was first recognized. In the United States alone, an estimated 1 million Americans are infected with the human immunodeficiency virus (HIV), the virus that causes AIDS; more than 150,000 individuals have been diagnosed with AIDS, and more than 100,000 deaths have been attributed to it.
People infected with HIV often have no symptoms for years. The eventual destruction of the immune system by HIV makes these persons particularly susceptible to the development of opportunistic infections (OIs), including a variety of viral, fungal, bacterial, and protozoal diseases. Herpes simplex virus (HSV) infections in persons infected with HIV usually occur as a result of the reactivation of virus that has been present in the body long before infection with HIV. HSV causes skin and mucous membrane infections in persons with HIV infection, just as it does in individuals with normal immune systems. In persons with HIV, however, these reactivated infections may be severe and protracted. Longstanding severe HSV lesions, in fact, can be one of the first symptoms of AIDS. Nonetheless, even in AIDS patients, HSV lesions typically remain localized and do not spread throughout the body.
The National Institute of Allergy and Infectious Diseases (NIAID) has principal responsibility in the federal government for research on AIDS. A major focus of the NIAID program is the development and evaluation of promising drugs to treat or prevent OIs, including HSV infections.
NATURE OF THE DISEASE
Two types of HSV can cause herpes or sores. HSV type 1 more commonly causes oral (on or near the mouth) herpes, also known as fever blisters or cold sores. Genital lesions are usually caused by HSV type 2 and may occur in the vaginal area, on the penis, around the anal opening, and on the buttocks or thighs. Occasionally, herpes lesions appear on other parts of the body that have come into direct contact with HSV type 1 or 2.
HSV infections in persons infected with HIV are common. The number of HSV infections that are resistant to the standard treatment appears to be increasing, and the resistant viruses can cause substantial local tissue destruction and discomfort.
Acyclovir, given by mouth or intravenously, provides both effective treatment and preventive therapy for HSV infections in persons with or without HIV infection. During recent years, however, there have been reports of HSV developing resistance to acyclovir. In persons with healthy immune systems, acyclovir resistance can be overcome by increasing the dose of the drug. Persons with damaged immune systems, such as those with HIV infection, are at increased risk of developing acyclovir-resistant HSV infections that will not heal despite maximal doses of drug. Because of the growing phenomenon of acyclovir resistance in persons with AIDS, alternative treatments are needed.
Other antiviral drugs are being tested for possible use in treating acyclovir-resistant HSV infections in persons with AIDS. Foscarnet, a drug that must be given intravenously, has been used with some success.
SCOPE OF THE NIH EFFORT
One of the primary goals of NIAID is the development of new therapeutic approaches for HIV-related OIs. The NIAID research effort ranges from preclinical study to clinical investigation in HIV-infected persons. NIAID has also given a high priority to basic research for finding better agents to treat infectious diseases associated with HIV. NIAID has established several National Cooperative Drug Discovery Groups (NCDDGs), specifically to identify and develop treatments for HIV-related OIs. Like the existing NCDDGs that focus on anti- HIV therapies, each NCDDG-OI consists of a multidisciplinary team with the skills needed to design, synthesize, and evaluate, at the preclinical level, potential therapeutic agents for the treatment of HIV-related OIs, including mucous membrane and skin HSV infections.
NIAID is conducting a number of clinical studies designed to evaluate agents for the prevention and treatment of several serious infections, including agents for the treatment of HSV infections. Studies are being conducted by the AIDS Clinical Trials Group (ACTG) and by the Collaborative Antiviral Study Group (CASG) at sites located at academic research centers throughout the country.
NIAID supports the following study of HSV infection: