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Treatments and drugs
By Mayo Clinic staffWhen HIV was first identified in the early 1980s, there were few drugs to treat the virus and the opportunistic infections associated with it. Since then, a number of medications have been developed to treat both HIV/AIDS and opportunistic infections. For many people, including children, these treatments have extended and improved their quality of life. Scientists at the National Institutes of Health estimate that since 1989, anti-retroviral medications have provided HIV-positive Americans with years of extended life. But none of these drugs can cure HIV/AIDS, many have side effects that can be severe, and most are expensive. What's more, after 20 years on AIDS drugs, some people develop resistance to the drugs and no longer respond to treatment. Newer drugs are being researched and created to help this group of people.
Treatment guidelines
A panel of leading AIDS specialists has developed recommendations for the use of anti-retroviral medications in people with HIV. These recommendations are based on the best information available at the time they were developed. AIDSinfo, a program of the U.S. Department of Health and Human Services, regularly refines and updates the recommendations as knowledge about HIV infection evolves.
According to current guidelines, treatment should focus on achieving the maximum suppression of symptoms for as long as possible. This aggressive approach is known as highly active anti-retroviral therapy (HAART). The aim of HAART is to reduce the amount of virus in your blood to very low or even nondetectable levels, although this doesn't mean the virus is gone. This is usually accomplished with a combination of three or more drugs.
But the treatment guidelines also emphasize the importance of quality of life. Thus the goal of AIDS treatment is to find the strongest possible regimen that is also simple and has the fewest side effects. If you have HIV/AIDS, it's important that you take an active role in treatment decisions. You and your doctor should discuss the risks and benefits of all therapies so that you can make an informed decision about what will likely be a complex and long-term treatment.
Anti-retroviral drugs
Anti-retroviral drugs inhibit the growth and replication of HIV at various stages of its life cycle. Seven classes of these drugs are available:
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Nucleoside analogue reverse transcriptase inhibitors (NRTIs). NRTIs were the first anti-retroviral drugs to be developed. They inhibit the replication of an HIV enzyme called reverse transcriptase. They include zidovudine (Retrovir), lamivudine (Epivir), didanosine (Videx), stavudine (Zerit) and abacavir (Ziagen). A newer drug, emtricitabine (Emtriva), which must be used in combination with at least two other AIDS medications, treats both HIV and hepatitis B.
The major side effect of zidovudine is bone marrow suppression, which causes a decrease in the number of red and white blood cells. Approximately 5 percent of people treated with abacavir experience hypersensitivity reactions such as a rash, fever, fatigue, nausea, vomiting, diarrhea and abdominal pain. Symptoms usually appear within the first six weeks of treatment and generally disappear when the drug is discontinued. If you've had a hypersensitivity reaction to abacavir, avoid taking the drug again. Side effects of emtricitabine include skin discoloration.
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Protease inhibitors (PIs). PIs interrupt HIV replication at a later stage in its life cycle by interfering with an enzyme known as HIV protease. This causes HIV particles in your body to become structurally disorganized and noninfectious. Among these drugs are saquinavir (Invirase), ritonavir (Norvir), indinavir (Crixivan), nelfinavir (Viracept), amprenavir (Agenerase), lopinavir/ritonavir (Kaletra), atazanavir (Reyataz) and tipranavir (Aptivus). Darunavir (Prezista) is intended for people who haven't responded to treatment with other drugs. Darunavir is used with ritonavir and other anti-HIV medications. Protease inhibitors are usually prescribed with other medications, to help avoid drug resistance.
The most common side effects of protease inhibitors include nausea, diarrhea and other digestive tract problems. PIs can also cause a significant number of side effects when they interact with certain other medications. That's because all PIs, to one degree or another, affect an enzyme system in your liver that is responsible for metabolizing a large number of drugs. Newer side effects have also appeared with the continuing and widespread use of protease inhibitors. These include elevated triglyceride levels and problems with sugar metabolism that may sometimes progress to diabetes.
There may also be abnormalities in the way fat is metabolized and deposited in your body. Some people lose much of their total body fat. Others gain excess fat on the back between their shoulders (buffalo hump) or in the stomach (protease paunch). No one knows exactly why these abnormalities occur. In fact, it's not even certain whether these problems are a direct result of treatment with protease inhibitors or due to some other cause that has yet to be identified. Similar metabolic abnormalities have occurred in people on anti-retroviral therapy that doesn't include PIs. Although these body changes can be distressing, the possibility they may occur should not stop you from getting treatment for HIV/AIDS.
- Non-nucleoside reverse transcriptase inhibitors (NNRTIs). These drugs bind directly to the enzyme reverse transcriptase. Four NNRTIs are approved for clinical use: nevirapine (Viramune), delavirdine (Rescriptor), efavirenz (Sustiva) and etravirine (Intelence). A major side effect of all NNRTIs is a rash. In addition, people taking efavirenz may have side effects such as abnormal and worsening of underlying mood disorders.
- Nucleotide reverse transcriptase inhibitors (NtRTIs). NtRTIs work much like nucleoside analogs: They interfere with the replication of reverse transcriptase and prevent the virus from inserting its genetic material into cells. But NtRTIs act more quickly than NRTIs do. The only approved drug in this class, tenofovir (Viread), inhibits both HIV and hepatitis B and appears to be effective in people who are resistant to NRTIs. The most common side effects of tenofovir, when used in combination with other anti-retrovirals, are nausea, vomiting, diarrhea and gas. As with all reverse transcriptase inhibitors, the possibility of severe, and even fatal, liver damage exists.
- Fusion inhibitors. One of the most alarming developments in the AIDS epidemic is the emergence of drug-resistant strains of HIV. Worldwide, a majority of people receiving treatment for HIV are resistant to at least one drug, and many don't respond to a typical three-drug combination. But a drug called enfuvirtide (Fuzeon), the first in a new class of drugs called fusion inhibitors, appears to suppress resistant strains of HIV. Fusion inhibitors stop the virus from replicating by preventing its membrane from fusing with the membrane surrounding healthy cells. Fuzeon is used in combination with other HIV drugs for people who have advanced infection and who have developed resistance to other drugs. Doctors administer Fuzeon by injection.
- Integrase inhibitors. These drugs are aimed at treating those who become resistant to other treatments. The only drug in this class, raltegravir (Isentress), is intended to be used in combination with other anti-retroviral drugs rather than alone. This is the first class of drugs that blocks replication of the HIV integrase enzyme, which keeps HIV DNA from inserting itself into human DNA. Common side effects include diarrhea, nausea, headache and fever.
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Chemokine co-receptor inhibitors. Chemokine co-receptor inhibitors (CCR5 antagonists) make up a new class of drugs used to treat a particulapr type of HIV infection called CCR5-tropic HIV-1. The only drug in this class — maraviroc (Selzentry) — is for treatment of CCR5-tropic HIV-1 in adults. Maraviroc is the first drug that targets a human protein rather than components of the HIV virus itself.
Maraviroc is used in combination with other anti-retroviral drugs for the treatment of adults with CCR5-tropic HIV-1 who have elevated levels of HIV (high viral load) in their blood despite treatment with other HIV medications. Maraviroc reduces viral load by preventing HIV from entering uninfected white blood cells. It does this by blocking CCR5, a major route of entry into the cells. CCR5 is a protein found on the surface of some immune cells, and maraviroc blocks the CCR5 co-receptor from accepting HIV.
During two large clinical trials, approximately twice as many people with CCR5-tropic HIV-1 infection who received maraviroc had undetectable viral loads after 24 weeks as did those who received more standard therapy in the control groups.
Side effects of maraviroc may include liver and cardiovascular problems, as well as cough, fever, upper respiratory tract infections, rash and abdominal pain.
Treatment response
Your response to any treatment is measured by viral load. Viral load should be tested at the start of treatment and then every three to four months while you're undergoing therapy. In some cases, you may be tested even more often.
New treatments
Many new drugs for HIV- or AIDS-related infections are in development or being tested in clinical trials.
For more information on new therapies, call AIDSinfo at 800-TRIALS-A (800-874-2572).
