Pneumocystis jiroveci pneumonia and HIV/AIDS

BACKGROUND

Pneumocystis jiroveci pneumonia (formerly called Pneumocystis carinii or PCP) is the most common opportunistic infection that occurs in AIDS patients. Originally, researchers thought a one-cell organism (protozoan) called Pneumocystis carinii caused the disease, but recent research suggests that a fungus called Pneumocystis jiroveci causes the pneumonia. However, the condition is still commonly referred to as PCP.

According to the U.S. Centers for Disease Control and Prevention (CDC), PCP is considered an AIDS-defining illness. This means that when HIV-infected patients develop PCP, their condition has progressed to AIDS.

Even if healthy individuals are exposed to Pneumocystis jiroveci, they do not typically develop PCP because they are able to inhibit the growth of the fungus. However, children and people with weakened immune systems, such as HIV/AIDS patients, are unable to adequately fight against the fungus.

Individuals with a CD4 cell (helper T-cells that help fight against disease and infection) count lower than 200 cells per microliter of blood have the greatest risk of developing PCP. Once the CD4 cell count falls below 200, the patient's condition has progressed to AIDS. Healthy individuals have a CD4 cell count between 600 and 1,200 per microliter of blood. In addition, people who have CD4 cell counts lower than 300 and have already had another opportunistic infection have an increased risk of developing PCP.

PCP almost always affects the lungs, causing a type of pneumonia. The first signs of PCP are difficulty breathing, fever, and a dry cough.

Mortality used to range from 20-40%, depending on the severity of the disease. Mortality rates have decreased to about 10-20%. This is because PCP is almost entirely preventable with new drugs, and it can be treated effectively with medication. Without HIV treatment, more than 85% of HIV/AIDS-infected patients would develop PCP.

Unfortunately, PCP is still common in people who are infected with HIV for a long time before getting treatment. In fact, 30-40% of AIDS patients develop PCP if they wait to get treatment until their CD4 cell counts are around 50 cells per microliter of blood.

Patients who are not infected with HIV have a higher mortality rate, which ranges from 30-50%, according to medical literature. The higher incidence of mortality is likely a result of a delay in diagnosis and initiation of appropriate treatment.

According to the CDC, healthcare providers should discuss preventative treatment with patients who have CD4 cell counts lower than 300.

CAUSES

The fungus called Pneumocystic jiroveci causes Pneumocystic jiroveci pneumonia (formerly called Pneumocystis carinii or PCP). The organism is widespread in the environment. Serologic evidence suggests that most healthy children have been exposed to the fungus by age three or four. However, it does not cause PCP in healthy individuals because their bodies are able to fend off the infectious organism.

The fungus affects individuals who have weakened immune systems due to cancer, HIV/AIDS, solid organ and/or bone marrow transplantation, as well as individuals receiving chronic corticosteroids or other medications that affect the immune system.

RISK FACTORS

AIDS patients with CD4 cell counts lower than 200 cells per microliter of blood who are not taking Pneumocystic jiroveci pneumonia (formerly called Pneumocystis carinii or PCP) preventative treatment have an increased risk of developing the condition.

HIV patients who have CD4 cell counts lower than 300 and have already had another opportunistic infection (infection that occurs in individuals with weakened immune systems) have an increased risk of developing PCP.

Patients who have primary immune deficiencies, including hypogammaglobulinemia and severe combined immunodeficiency (SCID), have an increased risk of developing PCP. Primary immune deficiencies are disorders that occur because part of the body's immune system does not function properly. These disorders are caused by intrinsic or genetic defects in the immune system.

Patients taking long-term immunosuppressive medications (such as Prograf©, CellCept©, Rapamune©, Neoral©, Sandimmune©, Gengraf© ,or Imuran©) for connective tissue disorders, vasculitides, and solid organ (heart, liver or kidney) transplant recipients are susceptible to PCP.

Patients with hematologic and nonhematologic malignancies (cancerous tumors), including solid tumors and lymphomas, have an increased risk of developing PCP.

Patients with severe malnutrition have an increased risk of developing PCP.

SYMPTOMS

General: The symptoms of Pneumocystic jiroveci pneumonia (formerly called Pneumocystis carinii or PCP) are nonspecific. PCP in HIV-infected patients tends to progress slower and present much later, often several weeks after symptoms appear, when compared with other immunocompromised patients.

Pulmonary symptoms: Symptoms may include shortness of breath (especially after physical activity), fever, nonproductive cough, chest discomfort, weight loss, chills, coughing up blood (rare), tachypnea (rapid breathing), tachycardia (fast heart rate), mild crackles (bubbling, or rattling sounds that occur when air moves through fluid-filled airways), cyanosis (bluish discoloration of the skin), nasal flaring, and intercostals retractions (visible use of muscles between the ribs that indicates labored breathing).

Extrapulmonary symptoms: While extrapulmonary symptoms (symptoms affecting areas of the body other than the lungs ) are rare with Pneumocystis, they may be present in patients who are receiving preventative PCP treatment with aerosolized pentamidine or in patients with advanced HIV infection who are not taking any prophylaxis. They may also occur in the absence of lung involvement. Extrapulmonary symptoms vary, depending on the affected organ(s). Almost any organ may become infected. The most common extrapulmonary symptoms include enlarged liver, skin lesions, enlarged lymph nodes, cloudy areas in the retina, and enlarged thyroid.

DIAGNOSIS

General: Preliminary blood tests and imaging studies are performed if Pneumocystic jiroveci pneumonia (also called PCP) is suspected. However, a diagnosis can only be confirmed by a microscopic identification of the organism in the lung. Samples may be taken from the patient's sputum or via bronchoalveolar lavage (BAL) or a lung biopsy. A lung biopsy is the most invasive test and should only be performed in rare cases when a BAL is non-diagnostic.

Bronchoalveolar lavage (BAL): Bronchoalveolar lavage is commonly performed to determine whether patients have PCP. During the procedure, a bronchoscope (thin, flexible tube) is passed through the mouth or nose into the lungs. Saline is then squirted into a small part of the lung and then collected for analysis. BAL is the most common invasive diagnostic test for PCP. This procedure is performed when PCP is strongly suggested, but the sputum sample is negative. The test has about 90% sensitivity and specificity, if performed correctly.

Chest X-ray: If PCP is suspected, a chest X-ray is usually conducted. If abnormalities like enlarged alveoli (air sacs in the lung) are detected, it may suggest PCP. However, a diagnosis can only be confirmed after the fungus is identified.

Lung biopsy: An open lung biopsy is the most invasive procedure, and it has 100% sensitivity and specificity because it provides the greatest amount of tissue for diagnosis. However, since a lung biopsy is the most invasive test, it should only be performed in rare cases when a BAL is non-diagnostic. The procedure is performed in a hospital while the patient is under general anesthesia. A tube will be placed through the mouth and into the airway that leads to the lungs. After cleaning the skin, the surgeon makes a cut in the chest area and removes a small piece of lung tissue. The wound is closed with stitches. A chest tube may be left in place for one to two days to prevent the lung from collapsing. The tissue sample is taken to a laboratory for a histological examination.

Sputum-induction for histopathologic testing: A sputum sample analysis can be conducted to determine whether a patient has PCP. The patient will cough deeply, expelling material that comes up from the lungs into a sterile cup. The sample is then taken to a laboratory and incubated under conditions that allow the fungus to grow. A positive culture will identify the disease-causing fungus. Sensitivity of a sputum analysis varies widely (50-90%), and depends on proficiency in using the technique and the experience of the laboratory. False negative results can occur if saliva is mistakenly cultured instead of sputum. These tests also take longer to produce definitive diagnostic results since the cultures need to be incubated for several days.

TREATMENT

General: For years, antibiotics, such as TMP/SMX, dapsone, pentamidine, and atovaquone, were prescribed to cancer patients with weakened immune systems who had Pneumocystic jiroveci pneumonia (also called PCP). It was not until 1985 that a small study proved that the antibiotics could also prevent and treat PCP in AIDS patients. Mortality rates of PCP in AIDS patients have declined by 50% since the antibiotics were introduced.

Because of the severity of the disease, many physicians will treat patients who show symptoms of PCP before a definitive diagnosis is made, if they belong to a high-risk group. Individuals with a CD4 cell (helper T-cells that help fight against disease and infection) lower than 200 cells per microliter of blood have the greatest risk of developing PCP. Once the CD4 cell count falls below 200, the patient's condition has progressed to AIDS. Healthy individuals have a CD4 cell count between 600 and 1,200 per microliter of blood. In addition, people who have CD4 cell counts lower than 300 and have already had another opportunistic infection have an increased risk of developing PCP.

Patients should tell their healthcare providers if they are taking any drugs (prescription or over-the-counter), herbs, or supplements due to possible interactions. Patients should take medications exactly as prescribed by their healthcare providers.

TMP/SMX (Bactrim© or Septra©: TMP/SMX (Bactrim© or Septra©) is a combination of two antibiotics: trimethoprim (TMP) and sulfamethoxazole (SMX). This drug is considered the most effective treatment for PCP. The drug is taken is taken orally. Patients typically take one single- or double-strength tablet daily. The SMX antibiotic is a sulfa drug, which many patients are allergic to. Cutting back from one pill a day to three pills a week reduces the risk of allergy. Allergic reactions to the drug usually cause a skin rash and sometimes a fever. Allergic reactions can be overcome using a desensitization procedure. Patients start with a very small amount of the drug and take increasing amounts until they can tolerate the full dose.

Dapsone: Dapsone is similar to TMP/SMX. Dapsone is almost as effective against PCP and TMP/SMX, and it causes fewer allergic reactions. Dapsone is taken orally. Once a day is the maximum dosage.

Pentamidine (NebuPent©, Pentam©, Pentacarinat©): Pentamidine (NebuPent©, Pentam© or Pentacarinat©) is a drug that is inhaled in an aerosol form to prevent PCP. Pentamidine can also be administered intravenously (IV) to treat active PCP. Patients receiving pentamidine must visit a clinic with a nebulizer once a month to receive treatment. The nebulizer is a machine that produces a very fine mist of the drug. The mist is inhaled directly into the lungs. The procedure takes about 30 to 45 minutes.

Atovaquone (Mepron©): Atovaquone (Mepron©) is a drug used in patients with mild or moderate cases of PCP who cannot take TMP/SMX or pentamidine. Atovaquone is a liquid drug that is taken by mouth. It is typically taken with food, every eight hours for 21 days.

Clindamycin (Cleocin©): Clindamycin has also been used to treat PCP. This drug is taken by mouth for about 21 days.

INTEGRATIVE THERAPIES

Note : Currently, there is a lack of scientific data on the use of integrative therapies for the treatment or prevention of Pneumocystis jiroveci pneumonia (formerly called Pneumocystis carinii or PCP) in patients with HIV or AIDS. The therapies listed below have been studied for related conditions, should be used only under the supervision of a qualified healthcare provider, and should not be used in replacement of other proven therapies or preventive measures.

Unclear or conflicting scientific evidence :

Chiropractic : Chiropractic is a healthcare discipline that focuses on the relationship between musculoskeletal structure (primarily the spine) and body function (as coordinated by the nervous system), and how this relationship affects the preservation and restoration of health. The broad term "spinal manipulative therapy" incorporates all types of manual techniques, including chiropractic. Although used with limited success, there is not enough reliable scientific evidence to draw a conclusion on the effects of chiropractic techniques in the management of pneumonia in the elderly.

Avoid with symptoms of vertebrobasilar vascular insufficiency, aneurysms, unstable spondylolisthesis, or arthritis. Avoid with agents that increase the risk of bleeding. Avoid in areas of para-spinal tissue after surgery. Avoid if pregnant or breastfeeding due to a lack of scientific data. Use extra caution during cervical adjustments. Use cautiously with acute arthritis, conditions that cause decreased bone mineralization, brittle bone disease, bone softening conditions, bleeding disorders, or migraines. Use cautiously with risk of tumors or cancers.

Chlorophyll : Chlorophyll is a chemoprotein commonly known for its contribution to the green pigmentation in plants, and is related to protoheme, the red pigment of blood. It can be obtained from green leafy vegetables (broccoli, Brussel sprouts, cabbage, lettuce, and spinach), algae (Chlorella and Spirulina), wheat grass, and numerous herbs (alfalfa, damiana, nettle, and parsley). Chlorophyll may help to regulate immunity in patients with active destructive pneumonia. Further studies are required to further elaborate on the immune-modifying effects of chlorophyll.

Avoid if allergic or hypersensitive to chlorophyll or any of its metabolites. Use cautiously with photosensitivity, compromised liver function, diabetes, or gastrointestinal conditions or obstructions. Use cautiously if taking immunosuppressants or antidiabetes agents. Avoid if pregnant or breastfeeding.

Iodine : Based on limited available clinical study, regular oropharyngeal application of povidone-iodine may decrease the prevalence of ventilator-associated pneumonia in patients with severe head trauma. Evidence in this area is not conclusive.

Reactions to iodine can be severe, and deaths have occurred. Avoid iodine-based products if allergic or hypersensitive to iodine. Do not use for longer than 14 days. Avoid Lugol solution and saturated solution of potassium iodide (SSKI, PIMA) with high amounts of potassium in the blood, pulmonary edema (fluid in the lungs), bronchitis, or tuberculosis. Avoid sodium iodide with gastrointestinal obstruction. Use cautiously when applying to the skin because it may irritate/burn tissues. Use sodium iodide cautiously with kidney failure. Iodine is considered safe in recommended doses for pregnant or breastfeeding women. Avoid povidone-iodine for perianal preparation during delivery or postpartum antisepsis.

Physical therapy : Early evidence suggests that chest physiotherapy techniques such as postural drainage, external help with breathing, percussion, and vibration are not better that receiving advice of deep breathing instructions in the treatment of serious pneumonia. Additional evidence is needed in this area.

Not all physical therapy programs are suited for everyone, and patients should discuss their medical history with their qualified healthcare professionals before beginning any treatments. Physical therapy may aggravate pre-existing conditions. Persistent pain and fractures of unknown origin have been reported. Physical therapy may increase the duration of pain or cause limitation of motion. Pain and anxiety may occur during the rehabilitation of patients with burns. Both morning stiffness and bone erosion have been reported in the literature, although causality is unclear. Erectile dysfunction has also been reported. Physical therapy has been used during pregnancy, and although reports of major adverse effects are lacking in the available literature, caution is advised nonetheless. All therapies during pregnancy and breastfeeding should be discussed with a licensed obstetrician/gynecologist before initiation.

Probiotics : Probiotics are beneficial bacteria (sometimes referred to as "friendly germs") that help to maintain the health of the intestinal tract and aid in digestion. They also help keep potentially harmful organisms in the gut (harmful bacteria and yeasts) under control. Most probiotics come from food sources, especially cultured milk products. Probiotics can be consumed as capsules, tablets, beverages, powders, yogurts, and other foods. Although some clinical studies support the use of probiotics for pneumonia, there is insufficient evidence to draw any firm conclusions.

Probiotics are generally considered safe and well-tolerated. Avoid if allergic or hypersensitive to probiotics. Use cautiously if lactose intolerant. Caution is advised when using probiotics in neonates born prematurely or with immune deficiency.

Sea buckthorn : Sea buckthorn (Hippophae rhamnoides) is found throughout Europe and Asia, particularly eastern Europe and central Asia. The plant's orange fruit and the oil from its pulp and seeds have been used traditionally for lung conditions, including coughing and phlegm reduction. Human study supports the use of sea buckthorn in pneumonia, although more clinical research is necessary.

Avoid if allergic or hypersensitive to sea buckthorn, its constituents, or members of the Elaeagnaceae family. Use cautiously in patients with cancer, high blood pressure, or bleeding disorders. Avoid doses higher than those found in foods if pregnant or breastfeeding.

Vitamin A : Limited available study did not find an effect of a moderate dose of vitamin A supplementation on the duration of uncomplicated pneumonia in underweight or normal-weight children aged younger than five years. However, a beneficial effect was seen in children with high basal serum retinol concentrations.

Avoid if allergic or hypersensitive to vitamin A. Vitamin A toxicity may occur if taken at high dosages. Use cautiously with liver disease or alcoholism. Smokers who consume alcohol and beta-carotene may be at an increased risk for lung cancer or heart disease. Vitamin A appears safe in pregnant women if taken at recommended doses; however, vitamin A excess, as well as deficiency, has been associated with birth defects. Use cautiously if breastfeeding because the benefits or dangers to nursing infants are not clearly established.

Vitamin C : Vitamin C (ascorbic acid) is a water-soluble vitamin that is necessary for the body form collagen in bones, cartilage, muscle, and blood vessels. It also aids in the absorption of iron. Vitamin C may play a role in pneumonia prevention. However, further research is needed.

Avoid if allergic or sensitive to vitamin C product ingredients. Vitamin C is generally considered safe in amounts found in foods. Vitamin C supplements are also generally considered safe in most individuals if taken in recommended doses. Avoid high doses of vitamin C with glucose 6-phosphate dehydrogenase deficiency, kidney disorders or stones, liver cirrhosis, gout, or paroxysmal nocturnal hemoglobinuria (bleeding disorder). It is unclear if vitamin C supplements in doses higher than Dietary Reference Intake recommendations are safe for pregnant or breastfeeding women. Vitamin C is naturally found in breast milk.

Yerba santa : Chumash Native Americans and other California tribes have used yerba santa (Eriodictyon californicum) and other related species (Eriodictyon crassifolium, Eriodictyon trichocalyx) for many centuries in the treatment of pulmonary (lung) conditions, saliva production, and to stop bleeding of minor cuts and scrapes. There is an extensive clinical history of the use of Eriodictyon extracts in pulmonary conditions such as influenza, bacterial pneumonia, asthma, bronchitis, and tuberculosis. However, additional study is needed.

Avoid if allergic or hypersensitive to Eriodictyon species. Use cautiously in children. Avoid if pregnant or breastfeeding.

Zinc : Results from large clinical trials suggest that supplementation with zinc may reduce the incidence of lower respiratory infections. However, a recent study does not support the use of zinc supplementation in the management of acute lower respiratory infections requiring hospitalization in indigenous children living in remote areas. Due to conflicting results, further research is needed before a conclusion can be drawn. Future studies could examine whether these adult populations have a similar response.

Zinc is generally considered safe when taken at the recommended dosages. Avoid zinc chloride because evidence of safety and effectiveness are currently lacking. Avoid with kidney disease. Use cautiously if pregnant or breastfeeding.

Fair negative scientific evidence :

Zinc : Limited available study found that zinc supplementation does not seem to lessen the duration of tachypnea, hypoxia, chest indrawing, inability to feed, lethargy, severe illness, or hospitalization for pneumonia in children.

Zinc is generally considered safe when taken at the recommended dosages. Avoid zinc chloride because evidence of safety and effectiveness are currently lacking. Avoid with kidney disease. Use cautiously if pregnant or breastfeeding.

Traditional or theoretical uses lacking sufficient evidence :

Bromelain : Bromelain is a digestive enzyme that comes from the stem and the fruit of the pineapple plant. Bromelain has been suggested as a potential treatment for pneumonia. It has demonstrated antibacterial effects against Escherichia coli (E.coli), but there is a lack of research evaluating its effects on Pneumocystis jiroveci.

Avoid if allergic to bromelain, pineapple, honeybee, venom, latex, birch pollen, carrots, celery, fennel, cypress pollen, grass pollen, papain, rye flour, wheat flour, or members of the Bromeliaceae family. Use cautiously with a history of bleeding disorders, stomach ulcers, heart disease, or liver or kidney disease. Use cautiously before dental or surgical procedures or while driving or operating machinery. Avoid if pregnant or breastfeeding.

Goldenseal : Goldenseal is one of the five top-selling herbal products in the United States. Berberine, a compound in goldenseal, has been found to have antimicrobial properties in animal and laboratory studies. Although goldenseal has been suggested as a potential treatment for pneumonia, there is currently a lack of research evaluating its effects on Pneumocystis jiroveci.

Avoid if allergic or hypersensitive to goldenseal or any of its constituents (like berberine and hydrastine). Use cautiously with bleeding disorders, diabetes, or low blood sugar levels. Avoid if pregnant or breastfeeding.

PREVENTION

General: Preventative antibiotics should be administered as a preventative treatment for Pneumocystic jiroveci pneumonia (also called PCP) in HIV patients who have CD4 cell counts lower than 200 cells per microliter of blood or with a history of Pneumocystis jiroveci pneumonia or oral thrush (fungal infection in the mouth). It may also be considered in patients who have a CD4 cell counter higher than 200 if their CD4 cell percentage is below 14%, they have other opportunistic infections, or they have a fever above 100 degrees Fahrenheit that has lasted for longer than two weeks. Preventative treatment can be discontinued if the patient's CD4 cell count increases above 200 cells per microliter of blood for at least three months, in response to antiretroviral therapy.

Since PCP occurs in individuals with a weakened immune system, HIV/AIDS patients should receive highly active antiretroviral therapy (HAART) to suppress the virus and restore the body's immune system.

TMP-SMX (Bactrim© or Septra©): Trimethoprim-sulfamethoxazole (Bactrim© or Septra©), also called TMP-SMX, is a combination of two antibiotics - trimethoprim and sulfamethoxazole. TMP-SMX is the standard preventative treatment for Pneumocystis jiroveci pneumonia. Patients typically take one single- or double-strength tablet daily. Allergic reactions to the drug usually cause a skin rash and sometimes a fever. Allergic reactions can be overcome using a desensitization procedure. Patients start with a very small amount of the drug and take increasing amounts until they can tolerate the full dose.

Dapsone: Patients who have a history of drug-induced allergic reactions may take dapsone instead. Dapsone is similar to TMP/SMX. Dapsone is almost as effective against PCP and causes fewer allergic reactions than TMP/SMX. 100 milligrams of Dapsone may be taken orally daily, or 50 milligrams may be taken orally twice a day.

Alternatively, 50 milligrams of dapsone may be taken orally once a day with 50 milligrams of oral pyrimethamine once per week and 25 milligrams of oral leucovorin once per week.

A third treatment option is 200 milligrams of dapsone with 75 milligrams of pyrimethamine and 25 milligrams of leucovorin once per week.

Atovaquone (Mepron©): Atovaquone (Mepron©) is a drug used in people with mild or moderate cases of PCP who cannot take TMP/SMX or pentamidine.

Highly active antiretroviral therapy (HAART): Currently there is no known cure for HIV/AIDS, but highly active antiretroviral therapy (HAART) has proven to effectively suppress the virus, which subsequently restores the body's immune system. HAART usually combines drugs from at least two different classes of antiretroviral drugs, and it has been shown to suppress the virus.

Currently, the U.S. Food and Drug Administration (FDA) has approved more than 30 antiretroviral drugs to treat HIV infected individuals. These drugs fall into six major classes: reverse transcriptase (RT) inhibitors, fusion inhibitors, protease inhibitors, entry inhibitors-CCR5 co-receptor antagonist, and HIV integrase strand transfer inhibitors. In July 2006, the FDA approved a multi-class combination called Atripla©.

Reverse transcriptase (RT) inhibitors disrupt the reverse transcription stage in the HIV lifecycle. During this stage, an HIV enzyme, known as reverse transcriptase, converts HIV RNA to HIV DNA. There are two main types of RT inhibitors - non-nucleoside RT inhibitors and nucleoside/nucleotide RT inhibitors.

Non-nucleoside RT inhibitors bind to reverse transcriptase, preventing HIV from converting the HIV RNA into HIV DNA. Approved non-nucleoside RT inhibitors include Intelence©, Rescriptor©, Sustiva©, and Viramune©.

Nucleoside/nucleotide RT inhibitors serve as faulty DNA building blocks. Once they are incorporated into the HIV DNA, the DNA chain cannot be completed. Therefore, the drugs prevent HIV from replicating inside a cell. Approved drugs include Combivir©, Emtriva©, Epivir©, Epzicom©, Hivid©, Retrovir©, Trizivir©, Truvada©, Videx EC©, Videx©, Viread©, Zerit©, and Ziagen©.

Fusion inhibitors prevent the virus from fusing with the cellular membrane, thus blocking entry into the cell. The fusion inhibitor Fuzeon© is FDA-approved.

Protease inhibitors (PIs) interfere with the protease enzyme that HIV uses to produce infectious viral particles. PIs prevent viral replication by inhibiting the activity of protease, an enzyme used by the virus to cleave nascent proteins for final assembly of new virons. FDA-approved protease inhibitors include Agenerase©, Aptivus©, Crixivan©, Fortovase©, Invirase©, Kaletra©, Lexiva©, Norvir©, Prezista©, Reyataz©, and Viracept©

Additionally, the FDA has approved Selzentry©, an inhibitor-CCR5 co-receptor antagonist, and Isentress©, an HIV integrase strand transfer inhibitor.

HAART can make the patient's CD4 cell count go up. If it goes over 200 and stays there for three months, it may be safe to stop taking PCP prophylactic antibiotics. However, because PCP medications are inexpensive and have mild side effects, some researchers think they should be continued until the CD4 cell count reaches 300.

AUTHOR INFORMATION

This information has been edited and peer-reviewed by contributors to the Natural Standard Research Collaboration (www.naturalstandard.com).

• AIDSMap Patient Information.www.aidsmap.com. Accessed April 17, 2009.
• National Institute of Allergy and Infectious Diseases. www.niaid.nih.gov. Accessed April 17, 2009.
• Natural Standard: The Authority on Integrative Medicine. www.naturalstandard.com. Copyright © 2009. Accessed April 17, 2009.
• The Body: The Complete HIV/AIDS Resource. www.thebody.com. Accessed April 17, 2009.