HIV Infection and AIDS

What Is HIV/AIDS?

Acquired immunodeficiency syndrome, better known as AIDS, is caused by infection with a virus known as human immunodeficiency virus (HIV). AIDS is the most advanced stage in the course of HIV infection. The virus attacks and destroys the body's immune system (the system that protects the body from disease). Without a fully working immune system, a person is at risk for getting other infections that usually do not affect healthy people. These are called opportunistic infections. There is also a greater risk of getting certain types of cancer, such as Kaposi sarcoma, lymphomas, and cervical cancer, as well as other cancer types. Many of these conditions can be life threatening.

The first cases of AIDS in the United States were reported in 1981. They were noted and described as a rare form of pneumonia in otherwise healthy homosexual men. A blood test for HIV infection was developed and approved in 1985. Around that same time, the virus was found worldwide.

What Causes AIDS?

The cause of AIDS is the human immunodeficiency virus (HIV). The virus was not known to cause AIDS until 1983.

The type of HIV responsible for most AIDS cases in the United States and Europe is called HIV-1. There is a second virus found mainly in Africa called HIV-2. Even though we commonly call the virus HIV in the United States, it is called HIV-1 in medical labs.

HIV transmission

HIV can be transmitted from one person to another when blood or certain body fluids (vaginal secretions, semen, or breast milk) from an infected person get into an uninfected person. Routes of transmission have included:

• unprotected vaginal, anal, or oral sex with an infected person
• needles and drug equipment shared with injection drug users who have HIV
• prenatal (before birth) and perinatal (during and right after birth) exposures of infants whose mothers are infected with HIV
• breast-feeding by mothers with HIV
• transfusion of blood products containing the virus
• organ transplants from HIV infected donors
• penetrating injuries or accidents of health care workers (usually needlesticks) while caring for HIV-infected patients or handling their blood

HIV is not spread by mosquitoes, ticks, or other insects. It can't be spread by casual contact such as talking, shaking hands, hugging, sneezing, sharing kitchen utensils or dishes, sharing bathrooms, sharing telephones or computers, or through water.

How Is HIV/AIDS Diagnosed?

People often believe that if they have had a physical exam, the doctor has checked for HIV. This is not usually true. Most of the time, HIV testing is not done unless you ask for it or have a medical situation that calls for testing. This may be changing, however. In late September 2006, the CDC issued guidelines for health care providers to begin routinely testing their patients aged 13 to 64 for HIV infection. The guideline noted that doctors were no longer required to counsel patients before the test.. Instead, the doctor should let the patient know that HIV testing will be included in routine blood testing. It is important to know that not all doctors follow guidelines such as this one. You may want to ask your primary care doctor whether his or her office performs routine HIV testing.

HIV testing is still more likely to be done if you have symptoms that look like AIDS, or if you are pregnant. The doctor or nurse will usually let you know that the test will be included along with other blood work. It is still fairly unusual for a person to be tested and not know it. There are a few cases where people are not told they are getting an HIV test. For instance, prisoners entering the penal system, people entering military service, and some people who apply for individual health or life insurance policies may be tested without knowing about it.

If you have any doubt about your HIV status, you might want to talk with your doctor or visit a health department clinic where testing is offered. To have the HIV test done without giving your name and address (anonymous testing), you can buy a home collection kit at the drugstore or go to a health department clinic that offers such testing. Most state health departments and a few other health sites offer anonymous HIV tests.

Because HIV infection often has no symptoms for years, a person can have HIV for a long time and not know about it until he or she is tested. People who do not seek HIV testing may not learn that they have HIV until they develop early symptoms or even AIDS. With proper testing, however, HIV infection can be detected easily and treated sooner.

Tests to detect HIV infection

HIV testing is available in many settings (hospitals, neighborhood clinics, health department clinics, doctors' and offices). HIV test kits that can be used at home are even available..

Understanding lab tests and results

Depending on where the test is done, it can take a few days to 2 weeks to get the results. Nearly all testing locations require that you return in person for your test results. Telephone results are usually given only for home kit testing, after the blood sample you mailed in is tested.

HIV is most often found using a pair of screening tests that look for antibodies to HIV in the blood. When the body is infected with HIV, it starts to make antibodies (immune system proteins) against the virus. Although these antibodies are not effective in getting rid of HIV, they can be found in the blood and some other body fluids within several weeks of infection. HIV tests look for these antibodies, not the virus itself (which would be much harder to detect).

In the United States, the first test used in most cases is called the HIV enzyme-linked immunosorbent assay (ELISA or EIA). This is a very sensitive test that can find antibodies to HIV in the blood. Because it is so sensitive, it sometimes finds "look-alike" substances that are not due to HIV, yielding a positive result in some people who may not have HIV. This is why a second test is used to confirm a positive ELISA test. This second test, known as a Western blot test, is done on the same sample of blood or body fluid.

If the ELISA test finds nothing, the HIV test result is reported as negative. This means that no trace of antibodies to HIV could be found. No further tests on the sample are needed.

If the ELISA result is positive, it is checked by using a more specific test, usually the Western blot test. If this test result is negative, it is very likely that the ELISA test gave a "false positive" result. The HIV test result is reported as negative, since antibodies to HIV were not found on this more specific test.

If both test results are positive, it means that the person is infected with HIV.

In rare cases, the Western blot test results come back not as positive or negative, but "indeterminate" (the test cannot tell if it is positive or negative). Sometimes, an indeterminate test means that the person has recently been infected with HIV but does not yet have enough antibodies to be sure. Most of the time, an indeterminate test result is caused by an unrelated condition. Because of this, people who have indeterminate results usually repeat the HIV test a few weeks later to find out whether they are actually infected.

The possible test results are outlined in the table below.

Table 1. How ELISA and Western Blot tests determine final HIV antibody test results

Treatment	ELISA result	Western Blot Result
Negative	Not done	Negative HIV test
Positive	Negative	Negative HIV test
Positive	Positive	Positive HIV test
Positive	Indeterminate	Indeterminate HIV test

It's important to note that a negative test result does not mean for sure that a person does not have HIV. It takes several weeks after becoming infected with the virus before enough antibodies are produced to be detected. To be sure that the person doesn't have the virus, he or she should be tested 3 to 6 months after the most recent suspected exposure.

Other lab tests: Other types of lab tests may be used to test for HIV. In general, these tests are used only in certain situations, such as when testing newborns (see section below).

• indirect immunofluorescence assay (IFA): For this test, a fluorescent dye is used to detect HIV antibodies in the blood.

• viral culture methods: Viral culture tests involve growing live HIV from infected cells. Viral culture was the first method ever used to detect the HIV virus itself instead of the antibody response, but it is slow and expensive.

• polymerase chain reaction (PCR): PCR is a very sensitive test by which the genes of a cell are increased many times to detect HIV viral DNA or RNA. This allows the PCR to look for the virus rather than the antibodies.

Types of tests for HIV

Blood test: This is the most common way to test for HIV. A blood sample is taken in a doctor's office, clinic, hospital, etc., and is tested with an ELISA test. If this is positive, a Western blot test is done on the same sample. Results usually take a few days to 2 weeks.

Oral fluid test: This test looks for HIV antibodies in fluid taken from the mouth. For this test, a special test pad is placed between the cheek and the gum for about 2 minutes. The pad absorbs fluid from the bloodstream through the membranes of the cheek. The sample is then analyzed by the ELISA test and confirmed, if needed, by the Western blot test. It may take a few days to 2 weeks to get these results.

Urine test: HIV antibodies are also present in small amounts in the urine. Thus, an ELISA-type test and Western blot test have been developed to detect HIV in the urine. Getting this test result also takes a few days to 2 weeks, depending on the lab.

Quick test: In 2004, the Food and Drug Administration (FDA) approved a faster test, the OraQuick Rapid HIV-1 Antibody Test. It is only used by trained staff, but it can detect antibodies to HIV in blood from a finger stick and provide results in less than 20 minutes. Positive results must be confirmed with a separate Western blot test, which can take several days after the second blood sample is taken. Negative results require no further testing (unless possible HIV exposure was recent and antibodies haven't had time to develop). The quick test is only offered in certain settings where specialized counseling and follow up tests can be done for people with positive results. This test can also be done on fluid taken from the mouth.

Home tests: There is also a home test approved by the FDA. There are a few HIV home test kits being advertised on the market today, but as of 2007 only the Home Access test system is FDA approved and legally marketed in the United States. The Home Access test has many pieces, including materials for specimen collection, a mailing envelope to send the specimen to a lab, and pre- and post-test counseling information.

This approved system uses a simple finger-stick process to collect blood at home. Blood is placed on a special paper in the kit and allowed to dry. The paper with the dried blood is mailed to a lab along with a personal identification number (PIN). It is tested by trained technicians in a certified medical lab the same way as samples taken in a doctor's office. The person who mailed in the test can call the toll-free number and give the PIN number to get their results and post-test counseling.

There are also home tests that are not FDA approved. These are advertised and sold in newspapers, magazines, and on the Internet, and often falsely claim that the tests are FDA approved or "manufactured in an FDA-approved facility." The advertisers of the unapproved HIV home test kits often claim that the presence of a visible sign, such as a red dot, within 5 to 15 minutes of taking the test shows a positive result for HIV infection. These unapproved test kits may use a finger-stick process to collect blood or a sponge for collecting saliva.

The blood or saliva sample is then placed in a plastic testing device containing some type of paper. A developing solution is added to find out if the sample is positive. The samples are not sent to a lab for professional testing. In 1999, the US Federal Trade Commission tested some samples of infected blood using unapproved test kits. All of the known HIV-positive blood samples tested negative. Although unapproved home tests may seem simpler and faster, they can give unreliable results. If you would like to know if a particular HIV test has been approved by the FDA, you can check their information sheet on the Internet at www.fda.gov/CbER/infosheets/hiv-home2.htm, or you can call them at 1-800-835-4709. You can also email them at octma@cber.fda.gov.

Testing newborns: Antibody tests are not helpful in newborns whose mothers are known to have HIV. Babies are born with their mothers' antibodies, which stay with them for several months. This means that any baby born to an HIV-infected mother will test positive for antibodies to HIV. This can be very confusing, because it means an infant's blood can test HIV-positive when the baby is not actually infected. Rather than wait a year or more for all of the mother's antibodies to go away, tests that detect the virus are used to find out whether an infant got HIV from its mother. It is important to find out quickly, because newborns with HIV can be treated early to help keep them from getting sick. Even with these tests, it may still take a few weeks to be certain of the infant's true HIV status.

Tests to diagnose AIDS and measure immune function

A diagnosis of AIDS is made when a person is shown to have HIV and impaired immune function. Impaired immunity is shown by certain opportunistic infections or cancers (see "The definition of AIDS" section), or when lab tests for CD4 cells show poor immune function. These kinds of tests are usually only done for those who are known to have HIV. People with HIV are tested every few months to help decide when to start treatment. They are also tested regularly after anti-HIV drugs are started, to be sure that the drugs are working as expected.

If a person has been diagnosed with AIDS based on a positive HIV test and a low CD4 count, he or she is still considered to have AIDS even if treatment later raises the CD4 count. If a person is diagnosed with AIDS based on a positive HIV test and having an AIDS-defining condition, he or she still has AIDS even if the AIDS-defining condition is later cured.

Immune profile, including CD4 counts: An immune profile, or immune panel, is a blood test that can be used to measure the loss of immunity and help decide on the best treatment. This profile usually includes counts of different types of cells in the blood (a complete blood cell count, or CBC). More important, it counts the number and percentage of CD4+ T lymphocytes. These are more commonly called CD4 cells, helper T cells, or T cells (see the section "The normal immune system").

The number of CD4 cells reflects the patient's stage of infection and is used to find out how much damage HIV has done to the immune system. It counts the number of CD4 cells in each cubic millimeter (mm³) of blood. A normal count in a healthy, HIV-negative adult can vary but is usually between 500 and 1,500 cells/mm³. (In babies and very young children the normal CD4 counts are much higher.) HIV infection lowers the CD4 count. People begin to get opportunistic infections or cancers more often as the count drops.

Viral load test (HIV-1 RNA): This test measures the amount of HIV that is found in a small amount of blood (the "viral load"). The viral load test is done after a patient has tested positive for HIV. Unlike the immune panel, this test does not show how much damage has been done to the immune system, so it cannot show whether a person has AIDS. It can show how quickly the HIV infection is likely to progress, however. A high viral load, even in a person with good T cell counts, suggests that the person may worsen quickly and become AIDS if not treated.

The viral load test is also often used to find out how well an infected person is responding to treatment. Doctors look for the viral load to go down and stay down while a person is taking anti-HIV drugs.

Viral load testing is done using polymerase chain reaction (PCR) or other lab techniques (see above). It is not normally used to find out if a person has HIV, because of its cost and other limitations. Sometimes, however, a week or two after being exposed, a person may start having symptoms that suggest early HIV (see Primary infection in the "The course of the disease" section). Because an HIV antibody test will probably not become positive for a few more weeks, a viral load is one kind of test that may be used right away in this unusual situation to find out if HIV is present. It is sometimes also used to diagnose infants who are born to HIV-infected mothers.

How Is HIV/AIDS Treated?

This information represents the views of the doctors and nurses serving on the American Cancer Society's Cancer Information Database Editorial Board. These views are based on their interpretation of studies published in medical journals, as well as their own professional experience.

The treatment information in this document is not official policy of the Society and is not intended as medical advice to replace the expertise and judgment of your cancer care team. It is intended to help you and your family make informed decisions, together with your doctor.

Your doctor may have reasons for suggesting a treatment plan different from these general treatment options. Don't hesitate to ask him or her questions about your treatment options.

First, find a doctor or clinician who has experience in treating people with HIV and AIDS. It is helpful to find someone you can talk to and feel safe with, since you will be seen fairly often. Even if you are not taking any prescribed HIV drugs, you will need to visit every 3 to 6 months for lab work and health checks.

Goals of treatment

Current treatment for HIV/AIDS has 3 main goals:

• restore and preserve immune function
• keep the amount of HIV in the body as low as possible for as long as possible
• prevent, cure, or control opportunistic infections

All of these help to support quality of life by improving health and lowering the chance of serious illnesses and their long-term effects.

Restoring and preserving the immune system: This is done is by using drugs that help stop HIV growth. In slowing viral growth in the body, the drugs also greatly help restore and preserve the immune system. This helps reduce the risk of some types of AIDS-related cancers. CD4 counts are checked often to be sure the drugs are working.

Other measures that can be taken to support the immune system involve good self-care, such as better nutrition, exercise, and stress management, and stopping tobacco or illicit drug use. Vaccines are usually recommended to prevent influenza (the flu), certain types of pneumonia, and some types of hepatitis. These work better if given before the CD4 count goes very low. There are some types of vaccines that people with HIV should not take. Be sure to talk with your doctor before you or any of the people you live with are vaccinated.

Keeping HIV levels in the body as low as possible for as long as possible: This is also done by using anti-HIV drugs. This treatment is usually started after the infection has damaged the immune system to the point that that the person is about to risk having a serious illness. Many studies have shown that effective anti-HIV drugs reduce illness and prolong life.

Before starting anti-HIV treatment, the doctor checks the immune system, tests for anti-retroviral resistance (see "Treatment problems with HAART" below), tests for suspected opportunistic infections, and looks for other diseases or conditions that could change the treatment. Counseling, education, and emotional and social support are normally offered as part of HIV care.

Preventing, curing, or controlling opportunistic conditions: You may be able to prevent some infections by avoiding exposure. For instance, your doctor may suggest avoiding large crowds and close contact with people who have fevers or other signs of infection. You can avoid other infections by preparing foods in ways that kill germs or keep them from growing. The risk of some infections may be lowered by letting someone else clean your aquariums, cat litter boxes, and bird cages. As a person's CD4 count drops below certain levels, however, antibiotics may be needed to prevent certain serious illnesses such as AIDS-related pneumonia. (See the section on "Prevention and treatment of opportunistic infections," and Table 2, Preventing Exposure and Illness Due To Infection in People with HIV/AIDS, showing CD4 counts.)

Opportunistic cancers cannot be prevented by using antibiotics. However, certain types of cancer seem less likely to develop when anti-HIV drugs are used. In women, cervical cancer may be prevented by getting regular Pap tests. When cancer occurs, its treatment depends on the type of cancer (see "Cancers in HIV infection" section below).

All opportunistic conditions can be serious and many are life-threatening. If signs of an opportunistic infection develop, such as fever, weakness, cough, shortness of breath, or pain, it is important to see your doctor quickly for diagnosis and treatment. Many opportunistic infections can be cured, and others can be controlled with drugs. Again, anti-HIV drugs are usually used along with treatments for the illness, to help the immune system and speed up recovery.

Anti-retroviral therapy

The main treatment for HIV at this time uses 3 or more drugs that help block new viruses from forming. Anti-HIV drugs are often called anti-retroviral drugs or ARVs (anti-retrovirals) because HIV is a type of retrovirus.

Combinations of anti-HIV drugs that are very good at stopping HIV growth are sometimes called highly active anti-retroviral therapy (HAART). Stopping or slowing the growth of HIV with these drugs helps improve the quality and length of the person's life.

The best anti-retroviral treatment combination varies with the person, disease stage, whether the person's infection is resistant to any anti-retroviral drugs, and other factors. Study after study has shown that with effective treatment using 3 or more drugs, people live longer and the disease progresses more slowly. However, no combination of drugs available at this time can actually get rid of all the HIV in your body.

When is anti-retroviral treatment started?

Anti-retroviral treatment should be started after you and your doctor discuss the risks and benefits of the drugs you are thinking about taking. The best time to start is not clear-cut, because HIV is an infection that usually progresses slowly.

Disease progression: Most doctors agree that anti-retroviral treatment should begin when:

• the HIV infection is causing significant symptoms (serious infections, cancers, or physical weakening), regardless of CD4 count and viral load.

• the CD4 level is below 350, even if there are no symptoms. Some doctors wait until the CD4 level nears 200 before starting the medicines.

People with viral loads over 100,000 are at risk of losing immune function, shown by a quicker drop in CD4 counts. These people may need to see the doctor more often to closely watch CD4 counts so that medicine can be started before the counts go too low. This is especially important as the counts are dropping down near the danger zone, in which the person is at higher risk for serious HIV-related conditions. Since older people are more likely to have these conditions, the need for treatment may be higher for them.

There may be other reasons to begin or delay treatment, and these should be discussed with your doctor. For example, the potential side effects of treatment may make you want to delay it for as long as possible. Or you may want to be treated before your CD4 counts drop to help preserve immune function and further reduce the risk of AIDS-related conditions.

Pregnancy: One very good reason to take anti-HIV drugs is pregnancy. Experts recommend that pregnant women take anti-HIV drugs, whether or not they are at a stage where they would normally be treated for their infection. These drugs are taken every day during pregnancy and delivery to reduce the baby's risk of being infected with HIV. The mother's viral load is watched carefully during pregnancy and kept as low as possible. After the baby is born, the mother may stop the HIV treatment drugs, depending on her HIV stage and situation. However, the baby is treated for a few weeks. The mother is advised not to breast-feed, since she can still pass on the infection in this way.

Kidney disease due to HIV (HIV nephropathy): Experts recommend that anyone who already has kidney problems caused by HIV take anti-HIV drugs to prevent further loss of kidney function. Treatment with anti-HIV drugs also improves survival.

People who are treated for hepatitis B infection: People with the hepatitis B virus (HBV) are often given lamivudine or emtricitabine. These 2 drugs actually started out as anti-HIV drugs, and are still used for treating HIV (see section below, "Antiretroviral drugs used to treat HIV and AIDS"). Doctors later learned that they were good for treating hepatitis B as well, so now the drugs are used for both infections. Unfortunately, if one of these drugs is given to treat HBV in a person who also has HIV, the HIV in the person's body can become resistant to the drug (see "Drug resistance" section below). Any resistance to HIV medicines makes HIV much harder to treat. Because of this, anyone who is going to get one of these HBV drugs should get a full set of HIV treatment drugs at the same time to prevent HIV drug resistance.

Primary HIV infection: For those few people whose infection is found within a few days or weeks after exposure (during primary HIV), doctors are still studying whether treatment at this stage might have long-term benefits by stopping certain types of immune system damage. If you are interested in being treated for HIV during this phase, you might want to think about entering a clinical trial (see the "Clinical trials" section).

Anti-retroviral drugs used to treat HIV and AIDS

More than 20 drugs have been approved to treat HIV infections and AIDS. They fall into 6 classes:

Nucleoside or nucleotide reverse transcriptase inhibitors (NRTIs) work by blocking the enzyme reverse transcriptase, which helps the virus make DNA from its RNA. Drugs in this class include:

• zidovudine (ZDV or AZT)
• abacavir (Ziagen^®)
• didanosine (Videx^®)
• emtricitabine (Emtriva^®)
• lamivudine (Epivir^®)
• stavudine (Zerit^®)
• tenofovir (Viread^®)
• zalcitabine (Hivid^®)

Non-nucleoside reverse transcriptase inhibitors (NNRTIs) work like the ones listed above, but they are chemically different and act on a different part of the reverse transcriptase molecule. There are 4 drugs in this class at this time:

• nevirapine (Viramune^®)
• delavirdine (Rescriptor^®)
• efavirenz (Sustiva^®)
• etravirine (Intelence™ or TMC-125)

Protease inhibitors (PIs) work differently from the drugs listed above. HIV produces an enzyme called protease in the late stages of its reproduction. The job of protease is to cut a large viral protein into usable sections as the newly-created viruses move out of the cells. When this protein is blocked by a protease inhibitor, the virus cannot be assembled properly. Protease inhibitors include:

• atazanavir (Reyataz^®)
• indinavir (Crixivan^®)
• nelfinavir (Viracept^®)
• ritonavir (Norvir^®)
• saquinavir (Fortovase^®)
• lopinavir (combined with ritonavir and called Kaletra^® – see information below on boosting)
• fosamprenavir (Lexiva^®)
• tipranavir (Aptivus^®)
• darunavir (Prezista^®, which must be taken with ritonavir – see boosting information, below)

Ritonavir has a special use as a protease-inhibitor booster. It was approved as an HIV treatment, and is used in standard doses as part of 3-drug combination treatments for HIV. Along with helping stop the virus, ritonavir was observed to keep certain other protease inhibitors and other drugs in the body longer.

Although ritonavir is still given in standard doses as a protease inhibitor, it is also used in smaller doses along with other protease inhibitors to take advantage of this side effect. This practice is called boosting a protease inhibitor, because it helps keep the drug levels in the body higher and often allows the drug to be given less often. When ritonavir is used solely as a booster, it is given in doses that are not high enough to affect the virus, but just enough to affect the level of the other drug. In this case, it is not being used as an anti-HIV drug, but only as a booster for one of the other drugs. It is important to know that even a small dose of ritonavir can also raise the levels of many other drugs, not just HIV treatment drugs. Anyone taking any dose of ritonavir must always find out about dangerous interactions before starting any new drug.

Entry inhibitors (including fusion inhibitors) work by blocking the virus from entering the host cell. One of the approved drugs, enfuvirtide (Fuzeon^®) is called a fusion inhibitor, and must be given by injection. The newer drug in this category is called maraviroc (Selzentry™). It helps to keep HIV out of individual CD4 cells by blocking the protein CCR5. This drug can only be used in patients with a strain of HIV that uses the protein CCR5 as its "door" into the CD4 cell. Before starting this drug, a person must be tested to be sure that the strain of HIV they have is the type this drug can stop.

Integrase inhibitors work by keeping the virus from putting its DNA into the host cell. This keeps the virus from being able to take over the cell to make more viruses. The only drug in this class is raltegravir (Isentress™).

Combination drugs are fixed-dose combinations of the above drugs that help to reduce the number of pills a person has to take. Some examples include:

• Combivir^® - zidovudine and lamivudine
• Trizivir^® - zidovudine, lamivudine, and abacavir
• Epzicom^® - abacavir and lamivudine
• Truvada^® - tenofovir and emtricitabine
• Atripla^® - efavirenz, emtricitabine, and tenofovir

Atripla is the first combination formula that comes in a single pill to be taken once a day. Although not everyone can take this combination, for those who can, it is a major improvement over taking several pills 3 or 4 times a day.

Treatment effectiveness

The success of any antiretroviral regimen is measured by checking the viral load a few weeks after the drugs are started, and then checking the viral load and CD4 count every 3 to 4 months as the drugs are continued. The CD4 count normally goes higher as the viral load goes down.

The goal of treatment is to get the viral load down so that the lab test cannot find any trace of virus in the blood (this is called an undetectable level). Different tests have different cutoffs for detection.

It is important to know that an undetectable virus load does not mean that there is no HIV in the person's blood, only that the test was not able to detect it. Undetectable virus levels do not mean that the person cannot infect others with HIV. Even with undetectable virus loads in the blood, it is still necessary to use safer sex practices and other precautions to avoid passing the virus on to others.

If the viral load cannot be kept down to undetectable levels with the first drug combination, others are usually tried. If no combination gets the viral load down to undetectable levels, doctors usually keep trying until they find a drug combination that will help keep it as low as possible. In such difficult cases, this may mean using more than 3 drugs.

Of the anti-retroviral drugs available today, many are used only after the preferred drugs have failed. Because researchers are still comparing treatments and new drugs are still being tested, the drugs and combinations used for HIV treatment continue to change as more research is completed.

HIV treatment issues

Drug resistance: Treating HIV infection is difficult, in part because the virus can change its proteins and become drug resistant. This means that the virus learns to multiply even when the anti-retroviral drugs are in your body. This is one reason that anti-retroviral drugs are never used alone or even in pairs – if HIV can grow even a little bit while a drug is in your system, those viruses often become more and more resistant to that drug. It usually takes the full effect of 3 drugs to stop HIV growth, so all of the anti-retroviral drugs must be taken on time in order to work properly. HIV can quickly become resistant to anti-retroviral drugs if they are not taken as prescribed.

Taking anti-HIV drugs exactly as prescribed can be hard for many people. Some drugs are taken 3 times a day, others once a day. Some don't work if they are taken with food, and others work better if they are taken with a meal. This can be confusing and complicated. It may take some time for a person to be ready for this kind of commitment. If you are not able to keep to a strict schedule, you need to discuss this with your doctor. You may be able to work out an easier regimen. Many doctors now try to start with combinations of drugs that can be taken once or twice a day. However, drug resistance testing may show that your options for effective treatment drugs are limited. If the first drug combination fails, or if you cannot take it, it becomes harder to find a second or third combination that works well. After a few drugs have failed, it may take more elaborate combinations of 4 or 5 drugs to try and keep the virus from growing.

Even when taken exactly as prescribed, people are likely to develop drug-resistant virus after years on the drugs. If the virus load begins to increase while the patient is taking anti-retroviral drugs correctly, a drug resistance test is usually done to learn which drug or drugs the virus is resistant to. Unfortunately, many of the HIV drugs are similar, and resistance to one drug may mean resistance to more drugs in the same class. This limits the number of drug combinations that a person might expect to use after one or more combinations fail. Some people have HIV that has already become resistant to all the drugs that are available today. It is also possible for a person with drug-resistant virus to transmit that virus to others. This means that an increasing number of people who get HIV find that they already have drug-resistant virus, even before they have taken any drugs to treat HIV.

Drug interactions: Another challenge of anti-retroviral drugs, especially the protease inhibitors, is that they can interact with other drugs. This means that one or more drugs might not work, or that one might build up to toxic levels in the body. For example, some anti-retroviral drugs interact with certain antibiotics, cholesterol-lowering drugs, anti-seizure drugs, birth control pills, erectile drugs, or even other anti-retrovirals. Each time a new drug is prescribed, your doctor and pharmacist should review all your drugs and supplements to be sure that no harmful interactions are likely. This can complicate treatment of many conditions.

As noted above, ritonavir interacts with many other drugs in ways that can be dangerous. However, some treatment regimens exploit this property of ritonavir by using fewer doses of certain other protease inhibitors to achieve the same effect. In cases such as this one, doses can be adjusted, but there are a few drugs that are simply not safe to use with some HIV drugs. This is one of the reasons it is important to keep a list of all your drugs, along with the dose and how often you take them, with you at all times. It also means that if you are taking one of these interacting drugs and stop taking it, you may need to have other drug doses adjusted back to the usual levels.

Side effects: Like all drugs, anti-retroviral drugs can have side effects. Short-term side effects show up within a few days or weeks, depending on the drug. They can range from nausea, vomiting, diarrhea, headaches, and rashes, to severe allergic reactions. Most of these effects only happen to a few people who take the drugs. Each drug has specific side effects, which need to be discussed with your doctor. But some side effects are typical of each class.

The NRTIs can cause acidosis of the blood, which is a serious chemical imbalance, in a few people. Acidosis can make you feel very weak and short of breath. This very rarely occurs, but if it happens, you need to see a doctor right away, preferably in an emergency room. A blood test can show if you have acidosis. NRTIs can also cause fatty changes in the liver, usually after 6 months or more. They can also cause lipodystrophy, a condition in which body fat can build up on the chest and abdomen and be lost from the arms and legs. These drugs lower blood counts and can cause fatigue, nausea, anemia, headaches, and other symptoms in some people. AZT causes the most problems with blood counts, although only in some patients.

Abacavir is also known for causing a type of allergic reaction that damages organs in certain people. Now, doctors can test for this reaction before this drug is even started. However, most side effects can be found only after a person starts taking the drug.

The NNRTIs can cause rashes and allergic reactions. They can also lead to liver damage, which is usually found through blood tests and is rarely a serious problem. The NNRTIs can also affect mood, thinking, and sleep patterns. One drug in this class, efavirenz, can cause birth defects if it is taken by pregnant women.

The PIs can also cause body fat to redistribute (lipodystrophy). Over the long term, they can raise blood levels of cholesterol and triglycerides and increase risk of heart attacks. They can raise blood sugar and even cause diabetes in some people. Cholesterol and blood sugar levels are checked regularly while a patient is on these drugs, and some people may require treatment if there are problems. It is important to reduce the risk of heart problems by avoiding tobacco, eating healthy, and staying active.

Entry inhibitors can cause serious rashes and allergic reactions with fevers, chills, trouble breathing, and faintness or dizziness. Maraviroc can cause liver damage in some people, with symptoms like jaundice (yellowing of the skin or eyes). Because enfuvirtide is injected, people can develop irritations or infections at the injection site.

Integrase inhibitors can cause milder symptoms such as nausea, headache, fever, and diarrhea. A few people develop a serious problem that shows up with muscle pain, weakness, and dark colored urine.

As part of follow-up with patients on HIV drugs, most doctors check labs often and watch for signs of diabetes, hyperlipidemia (high cholesterol and triglycerides), fat redistribution (lipodystrophy), liver damage, low blood counts, and other side effects that may worsen the longer the drugs are given. Some drugs cause very specific side effects that may go on even after the drug that caused them is stopped. In rare cases, side effects may be serious enough that the person may need some time in the hospital. Talk with your doctor or nurse about what you can do to reduce your risk of side effects. Find out which side effects need to be reported to the doctor right away and what to do if you should have these problems after office hours or on weekends.

Cost: Combination treatment can be costly (around $15,000 per person per year for the drugs alone, not including labs and doctor visits). It is important to talk with your doctor about what you can afford or what insurance will pay, as well as how likely you are to stick to the planned drug program. HIV drugs must be taken exactly as directed for them to work.

Guiding principles of treatment

In 1997, the Office of AIDS Research of the National Institutes of Health (NIH) brought together a panel of experts to discuss the advances in basic HIV research, treatment research, and testing in order to give the best information to doctors and patients. The final report presented the following principles that have guided treatment for a decade. They are summarized here because they offer some of the most important information about HIV and its treatment:

• HIV infection is always harmful, and true long-term survival without serious loss of immune function is unusual. When HIV continues to reproduce, it damages the immune system and leads to AIDS.

• Regular, periodic viral load tests and CD4 lymphocyte counts are necessary to find out when to start or change anti-retroviral therapy and to learn the risk of disease progression.

• The time to start HIV treatment should be based on risk of disease progression and amount of immune deficiency, and these vary with individual patients.

• The goal of treatment is to keep HIV from growing, so that it stays below levels that can be detected by viral load tests.

• The anti-retroviral drugs used in combination must be carefully chosen and given together.

• Each anti-retroviral drug in a combination treatment regimen should always be used according to the most effective schedules and dosages.

• Any change in a person's anti-retroviral treatment reduces future treatment options.

• Women should receive effective anti-retroviral therapy even when pregnant.

• The principles of anti-retroviral therapy presented above apply to both HIV-positive children and adults, although the treatment of HIV-positive children involves unique considerations.

• Persons with acute (primary) HIV infection may also benefit from combination anti-retroviral therapy to decrease the virus load to undetectable levels.

• All HIV-infected persons, including those with viral loads below detectable levels, should be considered infectious and should avoid sexual and drug-use behaviors linked to giving or getting HIV and other infections.

Treatment follow-up

Because of side effects, many people would like to sometimes stop therapy and take a short break. Most doctors think this is risky, and will not recommend it until clinical trials show this can be done safely. It is important that people getting treatment stick closely to their regimen (drug schedule). Missing doses of drugs allows the virus to grow back very quickly, and increases the risk of drug resistance. Stopping one anti-HIV drug while continuing to take the others may allow the virus to quickly develop resistance to the remaining drugs. (See the information on "Drug resistance" above.) If you are having problems with the regimen, talk to your doctors and find out if an easier one can be worked out.

Your doctor will check your blood counts, your CD4 counts, measure the viral load in your blood, and generally watch your health while you are on anti-retroviral drugs. At some point, your viral load may begin to creep up after it has been down for a while. This can happen quickly if you miss doses. It can also mean the virus is becoming resistant to one or more of the drugs you are on, and your doctor may test your blood to see which drugs will be most effective. It is not unusual for HIV to develop resistance, especially after a couple of years, and most people will need to change drug regimens at some point.