Antiretroviral Treatment of Human Immunodeficiency Virus (HIV) Infection

Side effects of combinations of antiretroviral medications 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 medications when needed. For most people, doctors can find a combination of medications 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 medications. Some skin reactions can be very dangerous, especially if the medication 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 medications 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 If the body did not have defenses against infection, it would quickly be overwhelmed by microorganisms. These defenses require a living, properly functioning body. A dead body begins to decay... 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 medications. 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 medications and other medications or between two antiretroviral medications can occur. Thus, people should make sure their doctor knows all the medications they are taking.

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

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

Antiretroviral treatment is beneficial only if the medications 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 antiretroviral 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 antiretroviral treatment. However, research has shown that people who are promptly treated with antiretroviral medications 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 medications as directed for a life time is demanding. Some people skip doses or stop taking the medications for a time (called a drug holiday). These practices are dangerous because they enable HIV to develop resistance to the medications.

Because taking HIV medications 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 medications as directed, doctors often prescribe treatment that combines two or more medications 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 medication is causing them. Stopping treatment is usually safe if all medications are stopped at the same time. Medications are restarted once the dose of the medication causing problems has been modified or another medication 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, abacavir 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, medications to prevent opportunistic infections are routinely prescribed, as in the following cases:

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

If insulin resistance develops, medications to increase sensitivity to insulin may help. If blood levels of cholesterol and triglycerides increase, lipid-lowering medications 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.