This is the main type of treatment for HIV or AIDS. It is not a, but it can stop people from becoming ill for many years. The treatment consists of drugs that have to be taken every day for the rest of a person’s life.

The aim of antiretroviral treatment is to keep the amount of HIV in the body at a low level. This stops any weakening of the immune system and allows it to recover from any damage that HIV might have caused already.

The drugs are often referred to as:

• Antiretrovirals
• Anti-HIV or Anti-AIDS Drugs
• HIV Antiviral Drugs
• ARVs

HIV/AIDS

Treatment of HIV Infection

Photo of a variety of
different drug treatments.
Credit: NIAID.

NIAID’s HIV/AIDS Treatment Research

AIDS stands for Acquired Immune Deficiency Syndrome. AIDS is a serious condition that weakens the body's immune system, leaving it unable to fight off illness.

AIDS is the last stage in a progression of diseases resulting from a viral infection known as the Human Immunodeficiency Virus (HIV or AIDS virus). The diseases include a number of unusual and severe infections, cancers and debilitating illnesses, resulting in severe weight loss or wasting away, and diseases affecting the brain and central nervous system.

There is no for HIV infection or AIDS nor is there a vaccine to prevent HIV infection. However, new medications not only can slow the progression of the infection, but can also markedly suppress the virus, thereby restoring the body's immune function and permitting many HIV-infected individuals to lead a normal, disease-free life.

Description of AIDS and HIV Infection
The immune system is a network of cells, organs and proteins that work together to defend and protect the body from potentially harmful, infectious microorganisms (microscopic life-forms), such as bacteria, viruses, parasites and fungi. The immune system also plays a critical role in preventing the development and spread of many types of cancer.

When the immune system is missing one or more of its components, the result is an immunodeficiency disorder. AIDS is an immunodeficiency disorder.

Lymphocytes (white blood cells) are one of the main types of immune cells that make up the immune system. There are two types of lymphocytes: B cells and T cells. (T cells are also called CD4 cells, CD4 T cells, or CD4 cell lymphocytes). B cells secrete antibodies (proteins) into the body's fluids to ambush and attack antigens (foreign proteins such as bacteria, viruses or fungi). T cells directly attack and destroy infected or malignant cells in the body.

There are two types of T cells: helper T cells and killer T cells. Helper T cells recognize the antigen and activate the killer T cells. Killer T cells then destroy the antigen.

When HIV is introduced into the body, this virus is too strong for the helper T cells and killer T cells. The virus then invades these cells and starts to reproduce itself, thereby not only killing the CD4 T cells, but also spreading to infect otherwise healthy cells.

The HIV virus cannot be destroyed and lives in the body undetected for months or years before any sign of illness appears. Gradually, over many years or even decades, as the T cells become progressively destroyed or inactivated, other viruses, parasites or cancer cells (called "opportunistic diseases") which would not have been able to get past a healthy body's defense, can multiply within the body without fear of destruction. Commonly seen opportunistic diseases in persons with HIV infection include: pneumocystis carinii pneumonia, tuberculosis, candida (yeast) infection of the mouth, throat or vagina, shingles, cytomegalovirus retinitis and Kaposi's sarcoma.

Causes and Risk Factors of AIDS and HIV Infection

• extreme fatigue
• rapid weight loss from an unknown cause (more than 10 lbs. in two months for no reason)
• appearance of swollen or tender glands in the neck, armpits or groin, for no apparent reason, lasting for more than four weeks
• unexplained shortness of breath, frequently accompanied by a dry cough, not due to allergies or smoking
• persistent diarrhea
• intermittent high fever or soaking night sweats of unknown origin
• a marked change in an illness pattern, either in frequency, severity, or length of sickness
• appearance of one or more purple spots on the surface of the skin, inside the mouth, anus or nasal passages
• whitish coating on the tongue, throat or vagina
• forgetfulness, confusion and other signs of mental deterioration

• Candidiasis
• Cervical cancer (invasive)
• Coccidioidomycosis, Cryptococcosis, Cryptosporidiosis
• Cytomegalovirus disease
• Encephalopathy (HIV-related)
• Herpes simplex (severe infection)
• Histoplasmosis
• Isosporiasis
• Kaposi's sarcoma
• Lymphoma (certain types)
• Mycobacterium avium complex
• Pneumocystis carinii pneumonia
• Pneumonia (recurrent)
• Progressive multifocal leukoencephalopathy
• Salmonella septicemia (recurrent)
• Toxoplasmosis of the brain
• Tuberculosis
• Wasting syndrome

1. Nonnucleoside Reverse Transcriptase Inhibitors (NNRTIs), such as nevirappine (Viramune) and efavirenz (Sustiva), bind to and block the action of reverse transcriptase, a protein that HIV needs to reproduce.
2. Nucleoside Reverse Transcriptase Inhibitors (NRTIs), such as zidovudine (Retrovir), tenofovir DF (Viread), and stavudine (Zerit), are faulty versions of building blocks that HIV needs to make more copies of itself. When HIV uses an NRTI instead of a normal building block, reproduction of the virus is stalled.
3. Protease Inhibitors (PIs), such as lopinavir/ritonavir (Kaletra), disable protease, a protein that HIV needs reproduce itself.
4. Fusion Inhibitors, such as enfuvirtide (Fuzeon ), are newer treatments that work by blocking HIV entry into cells.

• Don't have sexual contact with anyone who has symptoms of AIDS or who is a member of a high risk group for AIDS.
• Avoid sexual contact with anyone who has had sex with people at risk of getting AIDS.
• Don't have sex with prostitutes.
• Avoid having sex with anyone who has multiple and/or anonymous sexual partners.
• Avoid oral, genital and anal contact with partner's blood, semen, vaginal secretions, feces or urine. Unless they know with absolute certainty that their partner is not infected, a latex condom should be used during each sexual act, from start to finish. The use of a spermicidal agent may provide additional protection.
• Avoid anal intercourse altogether.
• Don't share toothbrushes, razors or other implements that could become contaminated with the blood of anyone who is or might be infected with the AIDS virus.
• Exercise caution regarding procedures, such as acupuncture, tattooing, ear piercing, etc., in which needles or other nonsterile instruments may be used repeatedly to pierce the skin and/or mucous membranes.
• Such procedures are safe if proper sterilization methods are employed or disposable needles are used. Ask what precautions are taken before undergoing such procedures.
• If an individual is scheduling surgery in the near future, and is able, they could consider donating blood for their own use. This will eliminate completely the already very small risk of contracting AIDS through a blood transfusion. It will also eliminate the risk of contracting other bloodborne diseases (such as hepatitis) from a transfusion.

• Get professional help for terminating the drug habit.
• Do not share needles or syringes. Be aware that some street sellers are resealing previously used needles and selling them as new.
• Clean the needle before using.
• Some people apparently remain well after infection of the AIDS virus. They may have no physically apparent symptoms of illness. However, if proper precautions are not used with sexual contacts and/or intravenous drug use, these infected individuals can spread the virus to others.
• Anyone who thinks he or she is infected, or who is involved in high-risk behaviors, should not donate his/her blood, organs, tissues, or sperm as they may now contain the AIDS virus.

• What tests need to be done to diagnose this condition?
• How accurate is the test?
• Does a positive test mean AIDS?
• What type of treatment will you be recommending?
• How successful is it?
• Will you be prescribing any medications to prevent the development of some AIDS related infections?
• Are there any alternative treatments available?
• Are there experimental protocols in which I might participate?
• What are the chances of remaining well?
• For how long?
• Are there any support groups in the area?

Treatments and drugs

When 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 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:

• 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.

• 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.

• 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.