Treatment of HIV Infection: NIAID


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Article title: Treatment of HIV Infection: NIAID
Conditions: HIV
Source: NIAID
January 2002

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?

Sixteen drugs have been approved for treating 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. Antiretroviral drugs work by interfering with the virus' ability to use these enzymes. They fall into two categories.

  • Reverse transcriptase 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 interfere with the protease enzyme that HIV uses to produce infectious viral particles.
Drugs Approved for HIV Infection

    Nucleoside/Nucleotide
    RT Inhibitors
  • abacavir
  • ddC
  • ddI
  • d4T
  • 3TC
  • ZDV
  • tenofovir
    Non-nucleoside
    RT Inhibitors
  • delavirdine
  • nevirapine
  • efavirenz
    Protease
    Inhibitors
  • ritonavir
  • saquinavir
  • indinavir
  • amprenavir
  • nelfinavir
  • lopinavir

Do antiretroviral drugs cure HIV infection?

No, the currently available drugs cannot cure HIV infection. This is because HIV can become resistant to any one drug. Researchers initially attacked this problem by using 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. These new problems have not been seen before in people who have been infected with the virus for a long time.

What kind of problems do antiretroviral drugs cause?

People with HIV must take complicated treatment regimens, often taking several drugs on a daily basis. Patients may forget to take their medicine, find the food restrictions difficult to deal with, and may experience unpleasant side effects.

Aside from the complicated dosing regimens, antiretroviral drugs themselves may cause serious medical problems. Metabolic changes are occurring in people with chronic HIV infection. One of these changes causes HIV-associated lipodystrophy syndrome (HIV-LS). This condition results in abnormal fat distribution and cholesterol and glucose abnormalities. Gender and HIV infection itself can influence cell metabolism, making it difficult to distinguish adverse drug effects from the natural progression of the disease.

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. A disrupted mitochondrial energy supply can result in muscle wasting, heart failure, peripheral nerve damage causing numbness and pain, low blood cell counts, swelling and fatty degeneration of the liver, and inflammation of the pancreas. Other more general signs include fatigue, depression, and high lactic acid levels in the blood.

Osteonecrosis, or weakened bones, is another condition that is being seen more frequently in persons with HIV infection that may be a side effect of anti-HIV drugs.

What is NIAID doing to prevent complications from anti-HIV drugs?

To determine which drugs are responsible for HAART-associated toxicities, NIAID supports studies comparing the various drugs, alone and in combination. Strategies to reduce dependence on toxic drug regimens include

  • Using structured treatment interruption (STI) protocols
  • Combining immune-based therapies with HAART
  • Using studies to compare different dosing schedules, as well as early versus delayed treatment

Researchers also are evaluating combining, switching or avoiding regimens containing agents known to cause specific metabolic toxicities. Other strategies to minimize toxicity include specific interventions to treat HAART-associated complications. Such interventions include lipid-lowering agents for treatment of blood lipid abnormalities and testosterone supplementation for abdominal obesity in men.

In addition, researchers are following 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 the results of long-term use.

Through its Multi-center AIDS Cohort Study (MACS) program 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) program.

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

  • Fusion inhibitors -- drugs that interfere with HIV's ability to enter a cell
  • Integrase inhibitors -- drugs that interfere with HIV's ability to insert its genes into a cell's normal DNA.

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.


NIAID is a component of the National Institutes of Health (NIH). NIAID supports basic and applied research to prevent, diagnose, and treat infectious and immune-mediated illnesses, including HIV/AIDS and other sexually transmitted diseases, tuberculosis, malaria, autoimmune disorders, asthma and allergies.

Press releases, fact sheets and other NIAID-related materials are available on the NIAID Web site at http://www.niaid.nih.gov/default.htm.

Prepared by:
Office of Communications and Public Liaison
National Institute of Allergy and Infectious Diseases
National Institutes of Health
Bethesda, MD 20892

Public Health Service
U.S. Department of Health and Human Services


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