Treatment of HIV Infection
When AIDS was first recognized in 1981, patients with the disease were unlikely to live longer than a year or two. Since then, scientists have developed an effective arsenal of drugs that can help many people infected with HIV (human immunodeficiency virus) live longer and healthier lives. The treatment and prevention of HIV is a high priority for the National Institute of Allergy and Infectious Diseases (NIAID). Research supported by NIAID has greatly advanced our understanding of HIV and how it causes AIDS. This knowledge provides the foundation for NIAID's AIDS research effort and continues to support studies designed to further extend and improve the quality of life of those infected with HIV.What drugs have been developed for HIV infection?
Twenty drugs have been approved for treating individuals with HIV infection. They are called antiretroviral drugs because they attack HIV, which is a retrovirus.
Once inside the cell, HIV uses specific enzymes to survive. The first approved classes of antiretroviral drugs that were approved work by interfering with the virus' ability to use these enzymes. They fall into two categories:
- Reverse transcriptase (RT) inhibitors. RT inhibitors
interfere with an enzyme called reverse transcriptase or RT that HIV
needs to make copies of itself. There are two main types of RT inhibitors,
and they each work differently.
- Nucleoside/nucleotide drugs provide faulty DNA building blocks, halting the DNA chain that the virus uses to make copies of itself.
- Non-nucleoside RT inhibitors bind RT so the virus cannot carry out its copying function.
- Protease inhibitors (PI). Protease Inhibitors interfere with the protease enzyme that HIV uses to produce infectious viral particles.
The newest class of antiretroviral drugs works by changing the shape of the gp41 envelope protein surrounding HIV. This class of drug is called fusion inhibitors.
- Fusion inhibitors interfere with the virus' ability to fuse with and enter the host cell.
| Nucleoside/Nucleotide RT Inhibitors | Non-nucleoside RT Inhibitors | Protease Inhibitors | Fusion Inhibitors |
|---|---|---|---|
| abacavir | delavirdine | ritonavir | pentafuside |
| ddC | nevirapine | saquinavir | |
| ddI | efavirenz | indinavir | |
| d4T | amprenavir | ||
| 3TC | nelfinavir | ||
| ZDV | lopinavir | ||
| tenofovir | atazanavir | ||
| entricitabine | |||
| fosamprenavir calcium |
Do antiretroviral drugs cure HIV infection?
No, the currently available drugs cannot cure HIV infection. This is because the current drugs can suppress HIV but are unable to eliminate it from the body. Since HIV can become resistant to any one drug, researchers use a combination of antiretroviral drugs to suppress the virus. By combining both RT inhibitors and protease inhibitors, NIAID-supported research groups and drug companies developed the potent and effective combination therapy called highly active antiretroviral therapy or HAART.
Although the use of HAART has greatly reduced the number of deaths due to AIDS, this powerful combination of drugs cannot suppress the virus indefinitely. In addition, while people with HIV are living longer, new medical problems are surfacing. Even those individuals who take antiretroviral drugs can pass on HIV to others through unprotected sex.
What problems are associated with antiretroviral drug use?
People with HIV must take medicines with complicated regimens, often taking several drugs per day, some of which may require the person to fast. Patients may have difficulty adhering to these complicated regimens, find the food restrictions difficult to deal with, and may experience unpleasant side effects such as nausea and vomiting.
Aside from the complicated dosing regimens, antiretroviral drugs themselves may cause significant medical problems. Metabolic changes occur in people with HIV infection. Some of these changes may be related to the antiretrovirals, and may include abnormal fat distribution, abnormal lipid and glucose metabolism, and bone loss.
Some anti-HIV drugs are toxic to mitochondria, the energy producers in cells. Tissues that require high levels of energy, like muscles and nerves, are most susceptible to the affects of damaged mitochondria. Muscle wasting, heart failure, nerve damage, degeneration of the liver, and inflammation of the pancreas may be associated with mitochondrial damage.
What is NIAID doing to address the complications of anti-HIV drugs?
- Structured treatment interruption (STI) protocols
- Use of immune-based therapies with HAART
- Studies to compare different dosing schedules
- Studies to compare early versus delayed treatment
NIAID also supports projects evaluating regimens containing agents associated with toxicities. For example, NIAID funded researchers are investigating treatments for some metabolic complications. There are ongoing studies evaluating various treatments of fat redistribution, lipid and glucose abnormalities and bone loss.
In addition, researchers are studying the metabolic effects of various antiretroviral regimens in pregnant women and their infants and in HIV-infected children and adolescents, and include long-term follow up of such patients.
How does research ensure safety?
NIAID supports the development and testing of new classes of antiretroviral compounds or combinations that will be able to continuously suppress the virus with few side effects. Such studies will provide accurate and extensive information about the safety of the new agents and combinations. They will identify potential uncommon, but important, toxicities of newly approved agents. Studies are also underway to assess rare toxicities of older approved agents, especially as a result of long-term use.
Through its Multi-center AIDS Cohort Study (MACS) and the Women's Interagency HIV Study (WIHS), NIAID supports long-term studies of HIV disease in both men and women. Since their inception, these cohort studies have enrolled and collected data on more than 8,000 people. In addition to the information gleaned from this epidemiological goldmine, other studies on the specific metabolic complications of HIV treatment are supported through both the adult and pediatric AIDS Clinical Trials Groups (AACTG and PACTG) as well as through the Terry Beirn Community Programs for Clinical Research on AIDS (CPCRA).
Are any new drugs in the pipeline?
- The Pharmaceutical Research and Manufacturers Association lists nearly two dozen new anti-HIV drugs now in development. They include new protease inhibitors and more potent, less toxic RT inhibitors, as well as drugs that interfere with entirely different steps in the virus' lifecycle. These new categories of drugs include:
- Entry inhibitors - drugs that interfere with HIV's ability to enter cells.
- Integrase inhibitors-drugs that interfere with HIV's ability to insert its genes into a cell's normal DNA.
- Assembly and budding inhibitors-drugs that interfere with the final stage of the HIV life cycle, when new virus particles are released into the bloodstream.
- Cellular metabolism modulators-drugs that interfere with the cellular processes needed for HIV replication.
In addition, scientists are learning how immune modulators help boost the immune system's response to the virus and may make the existing anti-HIV drugs more effective. Therapeutic vaccines are also being evaluated for this purpose and could help reduce the number of anti-HIV drugs needed or the duration of treatment.
AIDSinfo, located at www.AIDSinfo.nih.gov, is a comprehensive resource for up-to-date information on government and industry sponsored HIV/AIDS treatment and prevention clinical trials. AIDSinfo also maintains the most current, federally approved guidelines for the treatment and prevention of HIV/AIDS and AIDS-related illnesses in adults and children, for the management of occupational exposure to HIV, and for the prevention of HIV transmission from mother-to-child during pregnancy. AIDSinfo has a great deal of information available in Spanish, and provides links to other Spanish language resources, which can be accessed through the home page.
AIDSinfo is sponsored by the National Institutes of Health: Office of AIDS Research, National Institute of Allergy and Infectious Diseases, National Library of Medicine; Centers for Disease Control and Prevention; Health Resources and Service Administration; and Centers for Medicare and Medicaid Services.
AIDSinfo
P.O. Box 6303
Rockville, MD 20849-6303
1-800-HIV-0440 (1-800-448-0440)
301-519-0459 (International)
1-888-480-3739 (TTY/TDD)
Monday to Friday, 12:00 p.m. to 5:00 p.m. Eastern Time
Spanish-speaking health information specialists are available
http://aidsinfo.nih.gov
For information specifically about clinical trials conducted by the NIAID Intramural AIDS Research Program, call 1-800-243-7644 (http://clinicaltrials.gov).
NIAID is a component of the National Institutes of Health (NIH), which is an agency of the Department of Health and Human Services. NIAID supports basic and applied research to prevent, diagnose, and treat infectious and immune-mediated illnesses, including HIV/AIDS and other sexually transmitted diseases, illness from potential agents of bioterrorism, tuberculosis, malaria, autoimmune disorders, asthma and allergies.
News releases, fact sheets and other NIAID-related materials are available on the NIAID Web site at http://www.niaid.nih.gov.
Prepared by:
Office of Communications and Public Liaison
National Institute of Allergy and Infectious Diseases
National Institutes of Health
Bethesda, MD 20892
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