Provided by National Institute of Allergy & Infectious Diseases

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.

Drugs Approved for HIV Infection

Nucleoside/Nucleotide RT Inhibitors

• abacavir
• ddC
• ddI
• d4T
• 3TC
• ZDV
• enofovir

Non-nucleoside RT Inhibitors

• delavirdine
• nevirapine
• efavirenz

Protease Inhibitors

• ritonavir
• saquinavir
• indinavir
• amprenavir
• nelfinavir
• lopinavir
• atazanavir
• entricitabine
• fosamprenavir
• calcium

Fusion Inhibitors

• pentafuside

  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?

  NIAID supports studies understanding the side effects of drugs or combinations of drugs as well as strategies to reduce exposure to potentially toxic drug regimens, such as:

  • 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).