When AIDS first appeared in the US, no drugs were available to treat it and few treatments existed for the opportunistic diseases that accompanied it. Over the last 10 years, therapies have been developed to fight both HIV infection and its associated infections and cancers. Because HIV belongs to the group of viruses called "retroviruses," drugs used to treat HIV infections are called antiretrovirals.

Current treatments^1,2

The first group of drugs approved to treat HIV infection are called reverse transcriptase (RT) inhibitors. They work by interrupting an early stage in the duplication (replication) cycle of the virus. This class of drugs includes AZT (zidovudine), ddC (zalcitabine), ddI (dideoxyinosine), d4T (stavudine), and 3TC (lamivudine). These drugs slow down the spread of HIV in the body and delay the start of opportunistic infections. However, they do nothing to prevent HIV from spreading to other people. Drugs called non-nucleoside reverse transcriptase inhibitors (NNRTIs) such as delvaridine (Rescriptor) and nevirapine (Viramune) are also available and used in combination with other antiretroviral drugs.

A second class of drugs has been approved more recently. These drugs, which are called protease inhibitors, interrupt virus replication at a later stage its cycle. They include ritonavir (Norvir), saquinivir (Invirase), indinavir (Crixivan), and nelfinavir (Viracept), and amprenavir (Agenerase).

Because HIV can become resistant to both classes of drugs, treatment consists of combination ("cocktail") therapy, using two or more drugs together, to inhibit the virus effectively.

Currently available drugs do not cure people of HIV infection or AIDS, and they all have side effects that can be severe. For example, AZT may destroy the body's supply of red or white blood cells, especially when taken in the later stages of AIDS. DdI can cause inflammation of the pancreas (the large gland behind the stomach, which plays an important role in digestion and sugar balance in the body) and painful nerve damage. Protease inhibitors are commonly associated with nausea, diarrhea, and other gastrointestinal symptoms. They can also interact with other drugs, causing serious side effects.

Several drugs are available to help treat the opportunistic infections which people with HIV infection are likely to get. These drugs include foscarnet and ganciclovir for cytomegalovirus (CMV) eye infections, fluconazole for yeast and other fungal infections, and TMP/SMX or pentamidine for a lung infection called Pneumocystis carinii pneumonia (PCP).

PCP is one of the most common and deadly opportunistic infections associated with HIV. To prevent PCP, adults whose CD4+ T-cell counts drop below 200 are given preventive therapy, in addition to antiviral treatment. Children are given PCP preventive therapy when their CD4+ T-cell counts drop below normal for their age group. Regardless of their CD4+ T-cell counts, any children and adults who survive an episode of PCP are given drugs for the rest of their lives to prevent the pneumonia from returning.

Individuals who develop Kaposi's sarcoma or other cancers are treated with radiation, chemotherapy, or injections of alpha-interferon, a genetically engineered form of a natural protein.

Current Treatments

Panretin (alitretinoin) gel 0.1% was approved on February 2, 1999 for the topical treatment of cutaneous lesions in patients with AIDS-related Kaposi's sarcoma.

Loss of appetite (anorexia) can be treated with two FDA-approved prescription medications: Marinol (dronabinol), a synthetic extract of marijuana; and Megace (megestrol acetate).

What are the latest developments in AIDS?

The anti-HIV drugs now available are expensive and difficult to use, they do not work well in everyone, and some patients cannot tolerate their side effects. Also, there is little hope that any of these drugs will completely clear the virus from a person's body. Today's treatments are not enough; new options must be developed.

Three new antiretrovirals are now available on an expanded-access basis (because there is not yet enough data on their use for marketing approval by the FDA): Abacavir, Efavirenz (Sustiva^TM), and adefovir dipivoxil (PREVEON^TM, bis-POM PMEA). Many other drugs for treatment of HIV infection or opportunistic infections are currently in development or being tested in clinical studies.

New types of protease inhibitors and reverse transcriptase (RT) inhibitors are being developed. These drugs which work at lower doses than current drugs and/or are active against a wider range of viruses (especially treatment-resistant ones).

A new class of drugs, integrase inhibitors, break down a chemical called integrase, which HIV needs to merge its genetic material with the cells of the infected person. One drug in this class (Zintevir^TM) is now in clinical trials.

Zinc finger inhibitors target the "zinc finger" structure in HIV which is not easily changed by mutation. Experimental forms of these drugs are now in early human testing.

Some of the treatments being studied involve new approaches to treating HIV infection, rather than traditional drugs. Among these are the use of "chemokines" which are made from human infections-fighting blood cells, to reduce levels of the toxic substances (cytokines) that HIV produces. Another approach uses a genetically engineered substance, T-20, which targets a step in the process by which HIV attaches to body cells. This approach has been shown to reduce the number of viruses in the infected person (viral load) and it is not likely to cause resistance. The main disadvantage is that T-20 will probably have to be given by continuous intravenous infusion, through a small pump worn like a pager.

Recently, advances have been made in the area of immunotherapy, where the body's own antibodies may be used to slow down the replication of HIV. The natural ability to fight off HIV is lost early in the infection process (or retained longer by some individuals who have slow progression of disease). Researchers are trying to learn how this response is lost and how to restore it by therapy.

What are last developments in AIDS Treatements

Antisense drugs are a 'mirror image' of part of the HIV genetic code. The drug locks onto the virus' genetic material to prevent it from functioning. One antisense drug, called HGTV43, is manufactured by Enzo Therapeutics, and is currently in Phase I trials.

For more information

For information about studies of new HIV therapies, call the AIDS Clinical Trials Information Service:

1-800-TRIALS-A

1-800-243-7012 (TDD/deaf access)