Antiretroviral medications used to treat human immunodeficiency virus (HIV) infection Human Immunodeficiency Virus (HIV) Infection Human immunodeficiency virus (HIV) infection is a viral infection that progressively destroys certain white blood cells and is treated with antiretroviral medications. If untreated, it can cause... read more aim to do the following:
Reduce the amount of HIV RNA (viral load) in the blood to an undetectable amount
Restore the CD4 count to a normal level
Several classes of antiretroviral medications are used together to treat HIV infection. These medications block HIV from entering human cells or block the activity of one of the enzymes HIV needs to replicate inside human cells and/or integrate its genetic material into human DNA.
The medications are grouped into classes based on how they act against HIV:
Reverse transcriptase inhibitors prevent HIV reverse transcriptase from converting HIV RNA into DNA. There are three types of these medications: nucleoside, nucleotide, and non-nucleoside.
Protease inhibitors prevent protease from activating certain proteins inside newly produced viruses. The result is immature, defective HIV that does not infect new cells.
Entry (fusion) inhibitors prevent HIV from entering cells. To enter a human cell, HIV must bind to a CD4 receptor and one other receptor, such as the CCR-5 receptor. One type of entry inhibitor, CCR-5 inhibitors, blocks the CCR-5 receptor, preventing HIV from entering human cells.
Post-attachment inhibitors also prevent HIV from entering cells but in a different way from fusion inhibitors. These are used mainly for HIV infection that is resistant to several other medications.
Integrase inhibitors prevent HIV DNA from being integrated into human DNA.
Attachment inhibitors prevent HIV from attaching to host T cells and other immune cells; thus they are unable to enter those cells.
Sites of Medication Action on Life Cycle of HIV
Medications used to treat HIV infection were developed based on the life cycle of HIV. These medications prevent HIV entry into its target cells or inhibit the three enzymes (reverse transcriptase, integrase, and protease) that the virus uses to replicate.
These medications prevent HIV from replicating in cells and significantly reduce the amount of HIV in the blood over a few days to weeks. If replication is sufficiently slowed, the destruction of CD4+ lymphocytes by HIV is decreased and the CD4 count begins to increase. As a result, much of the damage to the immune system caused by HIV can be reversed. Doctors can detect this reversal by measuring the CD4 count, which begins to return toward normal levels over weeks to months. The CD4 count continues to increase for several years but at a slower rate.
Early diagnosis of HIV infection is important because it enables doctors to identify people with HIV infection before their CD4 cell count decreases too much. The sooner people start taking antiretroviral medications, the more quickly their CD4 count is likely to increase and the higher the count is likely to become.
Did You Know...
HIV invariably develops resistance to any of these medications if they are used alone. Resistance develops after a few days to several months of use, depending on the medication and the virus. HIV becomes resistant to medications because of mutations that occur when it replicates.
Treatment is most effective when two or more medications are given in combination. These combinations of medications are often referred to as combination antiretroviral therapy (cART). cART is used because
Combinations are more powerful than single medications in reducing the amount of HIV in the blood.
Combinations help prevent the development of drug resistance.
Some HIV medications (such as ritonavir) boost the blood levels of other HIV medications (including most protease inhibitors) by slowing their removal from the body and thus increase their effectiveness.
cART can increase the CD4 count in people with HIV infection, thus strengthening their immune system and extending their life.
Side effects of antiretroviral medications
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:
Fat accumulates in the abdomen and breasts of women (called central obesity), and it is lost from the face, arms, and legs.
The body become less sensitive to insulin's effects (called insulin resistance)
Blood levels of cholesterol and triglycerides (two types of fat in the blood) are increased.
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.
Immune reconstitution inflammatory syndrome
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, which refers to the worsening of symptoms of an infection that doctors have already diagnosed
Unmasked IRIS, which refers to the first appearance of symptoms of an infection that doctors had not previously diagnosed
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.
Interactions with antiretroviral medications
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:
Grapefruit juice increases the levels of saquinavir, increasing the risk of side effects.
St. John's wort St. John’s Wort The reddish substance in the flowers of St. John’s wort contains numerous biologically active compounds, including hypericin and hyperforin. (See also Overview of Dietary Supplements.) People... read more (a medicinal herb) causes the body to process protease inhibitors and non-nucleoside reverse transcriptase inhibitors more quickly and thus makes them less effective.
Use of antiretroviral medications
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 medications as directed
Not skipping any doses
Taking the medications for the rest of their life
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.
Prevention of opportunistic infections
If the CD4 count is low, medications to prevent opportunistic infections are routinely prescribed, as in the following cases:
If the CD4 count drops below 200 cells per microliter of blood, the antibiotic trimethoprim-sulfamethoxazole is given to prevent Pneumocystis jirovecii pneumonia Overview of Pneumonia Pneumonia is an infection of the small air sacs of the lungs (alveoli) and the tissues around them. Pneumonia is one of the most common causes of death worldwide. The most common symptom of... read more . This antibiotic also prevents toxoplasmosis Toxoplasmosis Toxoplasmosis is infection caused by the protozoan parasite Toxoplasma gondii. Infection occurs when people unknowingly ingest toxoplasma cysts from cat feces or eat contaminated meat... read more , which can damage the brain.
If the CD4 count drops below 50 cells per microliter of blood, azithromycin taken weekly or clarithromycin taken daily may prevent Mycobacterium avium complex infections Mycobacterium avium Complex (MAC) Infections Many species of mycobacteria exist. The species Mycobacterium tuberculosis is the one that causes tuberculosis. The other mycobacteria species that cause disease are discussed here. These... read more . If people cannot take either of these medications, they are given rifabutin.
If cryptococcal meningitis 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 , pneumonia Overview of Pneumonia Pneumonia is an infection of the small air sacs of the lungs (alveoli) and the tissues around them. Pneumonia is one of the most common causes of death worldwide. The most common symptom of... read more , thrush Thrush Candidiasis is infection with the yeast Candida. Candidiasis tends to occur in moist areas of the skin. This skin infection may cause rashes, scaling, itching, and swelling. Doctors examine... read more , or a candidal infection in the vagina Vaginal Yeast Infection (Candidiasis) A vaginal yeast infection (also called candidiasis) is caused by an infectious organism called Candida, usually Candida albicans. A vaginal yeast infection may cause intense itching... read more recurs, people may be given the antifungal medication fluconazole for a long time.
If herpes simplex infections Herpes Simplex Virus (HSV) Infections Herpes simplex virus infection causes recurring episodes of small, painful, fluid-filled blisters on the skin, mouth, lips (cold sores), eyes, or genitals. This very contagious viral infection... read more of the mouth, lips, genitals, or rectum recur, people may require prolonged treatment with an antiviral medication (such as acyclovir).
Other medications may help with the weakness, weight loss, and central obesity that may result from HIV infection:
Megestrol and dronabinol (a marijuana derivative) stimulate appetite. Many people find that natural marijuana is even more effective, and its use for this purpose has been legalized in a few states.
If men have low testosterone levels plus fatigue, anemia, and/or muscle loss, they may be given testosterone by injection or through patches placed on the skin. Testosterone treatments can increase testosterone levels and lessen symptoms.
Growth hormone and tesamorelin (an injectable medication that releases growth hormone) reduce the central obesity that may result from HIV and its treatment.
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 cholesterol and/or triglycerides or a low level of high-density lipoprotein (HDL) cholesterol. Lifestyle, genetics, disorders (such as low thyroid hormone levels... read more (statins) can be used to lower them.
The following English-language resources may be useful. Please note that THE MANUAL is not responsible for the content of these resources.
Office of AIDS Research: Information from the National Institutes of Health (NIH), including a glossary of HIV-related terms and a drug database
The American Foundation for AIDS Research: Resources regarding the support of AIDS research, HIV prevention, treatment education, and advocacy
Centers for Disease Control and Prevention (CDC): HIV Treatment as Prevention: Information for patients about antiretroviral therapy used to reduce the amount of HIV in the body to keep the immune system working and prevent illness
Drugs Mentioned In This Article
|Select Brand Names
|Viramune, Viramune Suspension, Viramune XR
|Ziagen, Ziagen Solution
st. john's wort
|No brand name available
|Primsol, Proloprim, TRIMPEX
|Azasite, Zithromax, Zithromax Powder, Zithromax Single-Dose , Zithromax Tri-Pak, Zithromax Z-Pak, Zmax, Zmax Pediatric
|Biaxin, Biaxin XL
|Sitavig, Zovirax, Zovirax Cream, Zovirax Ointment, Zovirax Powder, Zovirax Suspension
|Megace, Megace ES
|Androderm, AndroGel, Andro-L.A., Aveed, AXIRON, Delatestryl, Depo-Testosterone, FORTESTA, JATENZO, KYZATREX, Natesto, STRIANT, Testim, Testoderm, Testopel, TLANDO, Virilon, Vogelxo, XYOSTED