Drug Treatment of Human Immunodeficiency Virus (HIV) Infection

Side effects of combinations of antiretroviral drugs may be unpleasant and serious. However, doctors can prevent many serious problems (such as anemia, hepatitis, kidney problems, and pancreatitis) by regularly examining the person and doing blood tests. The blood tests can detect side effects before they become serious and enable doctors to change antiretroviral drugs when needed. For most people, doctors can find a combination of drugs with minimal side effects.

Metabolism of fats may be disturbed, probably primarily by protease inhibitors. The following may result:

This combination of problems (called metabolic syndrome Metabolic Syndrome Metabolic syndrome is characterized by a large waist circumference (due to excess abdominal fat), high blood pressure, resistance to the effects of insulin (insulin resistance) or diabetes,... read more ) increases the risk of heart attacks, strokes, and dementia.

Rashes (skin reactions) are a side effect of many drugs. Some skin reactions can be very dangerous, especially if the drug causing the reaction is nevirapine or abacavir.

Mitochondria (structures within cells that generate energy) can be damaged when certain nucleoside reverse transcriptase inhibitors are used. Side effects include anemia, foot pain caused by nerve damage (neuropathy), liver damage that occasionally progresses to severe liver failure, and heart damage that can result in heart failure. Individual drugs differ in their tendency to cause these problems.

Bone density may decrease when cART is used, resulting in osteopenia or osteoporosis Osteoporosis Osteoporosis is a condition in which a decrease in the density of bones weakens the bones, making breaks (fractures) likely. Aging, estrogen deficiency, low vitamin D or calcium intake, and... read more . Most people with these disorders do not have any symptoms, but they are at higher risk of fracturing a bone.

The immune reconstitution inflammatory syndrome (IRIS) sometimes occurs when cART is successful.

In IRIS, symptoms of various infections worsen or appear for the first time because immune responses improve (are reconstituted), increasing inflammation Inflammation Natural barriers and the immune system defend the body against organisms that can cause infection. (See also Lines of Defense.) Natural barriers include the skin, mucous membranes, tears, earwax... read more at sites of infection. Symptoms sometimes worsen because parts of dead viruses persist, triggering immune responses.

There are two forms of this syndrome:

Paradoxical IRIS typically occurs during the first few months of treatment and usually resolves on its own. If it does not, corticosteroids, given for a short time, are often effective. Paradoxical IRIS is more likely to be severe when cART is started soon after treatment of an opportunistic infection is started. Thus, for some (but not all) opportunistic infections, cART is delayed until treatment of the opportunistic infection has reduced or eliminated the infection.

In people with unmasked IRIS, doctors treat the newly identified opportunistic infection with antimicrobial drugs. Occasionally, when the symptoms are severe, corticosteroids are also used. Usually, when unmasked IRIS occurs, cART is continued. An exception is when a cryptococcal infection Cryptococcosis Cryptococcosis is an infection caused by the fungus Cryptococcus neoformans or Cryptococcus gattii. People may have no symptoms or may have headache and confusion, a cough and... read more affects the brain. Then cART is temporarily interrupted until the infection is controlled.

Drug interactions Drug Interactions The effect a drug has on a person may be different than expected because that drug interacts with Another drug the person is taking (drug-drug interaction) Food, beverages, or supplements the... read more between antiretroviral drugs and other drugs or between two antiretroviral drugs can occur. Thus, people should make sure their doctor knows all the drugs they are taking.

Interactions between antiretroviral drugs may increase or decrease the effectiveness of the drugs.

Also, other substances affect how the body uses some HIV drugs. These substances include the following:

Antiretroviral treatment is beneficial only if the drugs are taken on schedule. Missing doses allows the virus to replicate and develop resistance.

Treatment cannot eliminate the virus from the body, although the HIV level often decreases so much that it cannot be detected in blood or other fluids or tissues. An undetectable level is the goal of treatment. If treatment is stopped, the HIV level increases, and the CD4 count begins to fall.

The best time to start drug treatment is as soon as possible, even if people are not sick and their CD4 count is still above 500 (normal is 500 to 1,000). Doctors used to wait until the CD4 count was below 500 to start drug treatment. However, research has shown that people who are promptly treated with antiretroviral drugs are less likely to develop AIDS-related complications and to die of them.

Before starting a treatment regimen, people are taught about the necessity of the following:

Taking the drugs as directed for a life time is demanding. Some people skip doses or stop taking the drugs for a time (called a drug holiday). These practices are dangerous because they enable HIV to develop resistance to the drugs.

Because taking HIV drugs irregularly often leads to drug resistance, health care practitioners try to make sure that people are both willing and able to adhere to the treatment regimen. To simplify the drug schedule and to help people take the drugs as directed, doctors often prescribe treatment that combines two or more drugs in one tablet that can be taken only once a day.

Doctors may stop treatment temporarily if people develop another disorder that requires treatment or if side effects are severe and doctors must determine which drug is causing them. Stopping treatment is usually safe if all drugs are stopped at the same time. Drugs are restarted once the dose of the drug causing problems has been modified or another drug is substituted for it and doctors determine that it is safe to restart treatment. An exception is abacavir. If people have had a fever or rash when they were taking abacavir, the drug should be permanently stopped. Such people may have a severe, potentially fatal reaction to abacavir if they take it again.

If the CD4 count is low, drugs to prevent opportunistic infections are routinely prescribed, as in the following cases:

Other drugs may help with the weakness, weight loss, and central obesity that may result from HIV infection:

If insulin resistance develops, drugs to increase sensitivity to insulin may help. If blood levels of cholesterol and triglycerides increase, lipid-lowering drugs Lipid-lowering drugs Dyslipidemia is a high level of lipids (cholesterol, triglycerides, or both) or a low high-density lipoprotein (HDL) cholesterol level. Lifestyle, genetics, disorders (such as low thyroid hormone... read more (statins) can be used to lower them.