Candidiasis is a fungal infection and among the most common conditions seen in people with HIV. While candidiasis is a rather common condition in general, it's often the first illness and sign that HIV disease is progressing to a more severe stage. Candidiasis outbreaks can be frequent, can cause great discomfort and can add to the decline of health in HIV disease.
Candidiasis can occur in the mouth, throat, windpipe, vagina or on the skin. It can also spread throughout the body. While this is rare, it is life-threatening. The most common places for infection are in the mouth and vagina. Recurrent and difficult to treat vaginal yeast infections are a sign of HIV disease progression in women.
This publication focuses on systemic candidiasis -- when it spreads throughout the body and may impact many systems. Project Inform materials are also available on Vaginal Candidiasis or Oral Candidiasis.
However, a weak immune system makes it easier for Candida to grow and cause infection. In HIV disease, the most serious Candida outbreaks occur when CD4+ cell counts are very low (below 100). In people with weak immune systems, candidiasis can recur and be difficult to treat.
Factors including diabetes, pregnancy, iron, folate, and vitamin B12 or zinc deficiency, and use of antihistamines can increase the risk of Candida infections. Things that may weaken the immune system -- from chemotherapy to stress and depression -- can also cause or worsen candidiasis.
If a person with thrush has problems swallowing (food "gets stuck") and/or has bad chest pain, he or she may also have esophageal infection. If symptoms do not improve with treatment, or if someone has problems swallowing but does not have thrush, an endoscopy is usually performed. This is when a doctor uses a small tube to look into the esophagus.
Systemic candidiasis is very difficult to diagnose. Candida in the blood may come from a local infection (like the mouth or site of a catheter) as well as from infection of internal organs. Candida may only briefly be present in the blood when an internal organ is infected, therefore a blood test result is not always reliable.
Products include amphotericin B (Fungizone), clotrimazole (Lotrimin), clotrimazole plus a steroid (Lotrisone), miconazole (Monistat-Derm), clotrimazole (Mycelex), nystatin plus a steroid (Mycolog-II), nystatin (Mycostatin), ketoconazole (Nizoral) and econazole (Spectazole). Creams containing a steroid should not be used for children under 12. Some creams can be bought over the counter and as a prescription. Over-the-counter products are usually labeled for treating athlete's foot or jock itch.
Ketoconazole (Nizoral) is taken at 200 or 400 mg once a day. It needs acid to be absorbed, so it should be taken with food. Antacids should be avoided. It should also not be taken at the same time as other therapies that may contain a buffer or antacid, like ddI (didanosine, Videx). It may not be well absorbed in people with gut problems or who cannot eat very much. Taking it with an acidic drink like a cola may help.
Fluconazole (Diflucan) is taken at 200 mg the first day, then 100 mg once a day thereafter. Treatment typically lasts two weeks for oral or skin candidiasis and three weeks for esophageal infection (or two weeks after symptoms clear up, whichever is longer). The dose may be increased to 400 mg per day if the lower dose does not work.
Studies suggest that fluconazole is more effective than ketoconazole. Some doctors still prefer to treat aggressive fungal infections with other drugs, like ketaconazole, in order to save the potent fluconazole for later use, if necessary. Resistance to fluconazole is well documented. Once it develops, then treatment options are very limited.
Itraconazole (Sporanox) appears to be at least as potent as ketoconazole and may be as good as fluconazole. It needs stomach acid to be absorbed, so it should be taken with food. The dose is 200 mg per day. If not enough drug is being absorbed, blood levels may need to be checked so the dose can be increased.
Itraconazole oral solution is more effective and puts higher levels of the drug in the blood than the capsule. There is a great potential for interactions between itraconazole and many anti-HIV drugs. For more information, read Project Inform's publication, Drug Interactions.
Fungizone (amphotericin B) is given directly into a vein. It's used to treat disseminated candidiasis when other systemic therapies fail or the infection is very aggressive. It is sometimes used with another drug, flucytosine, to treat specific fungal infections like cryptococcal infections.
This used to be the standard treatment for systemic or serious fungal infections. It lasted 8-12 weeks and often gave severe side effects, like kidney damage and anemia. People are now usually given amphotericin B until they start to improve (usually two weeks). They are then switched to fluconazole at 200-400 mg per day.
Other forms of amphotericin B are used when systemic infections become resistant or less responsive to standard therapy. These include amphotericin B colloidal dispersion (ABCD, Amphotec) and amphotericin B lipid complex (ABLC, Abelcet). These might have fewer side effects than standard amphotericin B, but all of them can be quite toxic.
In animal studies, using itraconazole or ketoconazole during pregnancy caused birth defects. There have also been four known infants born with severe skeletal problems to women who used fluconazole for an extended time while pregnant. It's presumed that these same risks apply to other oral azole drugs.
For treating or preventing oral or vaginal candidiasis, topical therapies like nystatin (Mycostatin, Pedi-Dri) may be preferable for pregnant women. For treating or preventing other fungal infections, like histoplasmosis, the Guidelines suggest amphotericin B, especially in the first trimester. It is also approved for treating thrush.
Although no formal studies have been performed, pregnant women have used amphotericin B without apparent harm to their unborn children. While amphotericin B may be preferable to azole therapy in pregnant women, it has possible severe side effects, including kidney toxicity and anemia.
Topical TreatmentsTopical creams and ointments may cause mild burning. Some people are highly sensitive and may have a widespread skin reaction with blisters and peeling. Some creams also contain a steroid to reduce inflammation that may cause itching, irritation or dryness. Vaginal tablets do not often cause problems, but in a few women they may lead to vaginal burning or itching or skin rash. Some women experience cramps or headaches.
Clotrimazole lozenges may cause minor changes in liver function, but this may not require stopping the drug. Oral irritation and nausea are rare side effects of nystatin lozenges. Nystatin oral rinse (Mycostatin) is nearly non-toxic, but it may cause gut problems if excessive doses are taken.
Systemic TreatmentsSide effects for the oral azole drugs are similar, but some studies show they're more common with itraconazole. The most common are nausea, vomiting and belly pain. Others include headaches, dizziness, drowsiness, fever, diarrhea, rash and changes in taste. The most serious problem is liver toxicity, but this is rare and usually reverses after the drug is stopped. Nevertheless, liver function should be checked closely, particularly with ketoconazole.
Amphotericin B has many side effects, some quite severe. Therefore, it is only used in cases when there's a direct threat to life or all other treatments have failed. Main side effects include kidney side effects and low red blood cells (anemia). Others include fever, chills, changes in blood pressure, changes in appetite, nausea, vomiting and headache. These reactions occur one to three hours after an infusion, are most severe with the first few doses, and diminish with later treatments. Side effects are generally the same with all amphotericin drugs, though ABCD and ABLC may be slightly less toxic.
Resistance to azole drugs has often required using amphotericin B. While potent and effective, amphotericin B is toxic, especially to the kidney. Newer versions, such as ABLC, Ambisome and Abelcet, have proven less toxic to the kidneys than the earlier formula. Moreover, a recent study comparing the earlier form to ABLC found that people tolerated ABLC better, which improved their ability to take the drug until the fungal infection successfully cleared. Even among people with some underlying kidney disease, ABLC was better tolerated, resulting in only very small changes in kidney function tests.
Nevertheless, recent studies show that exposure to azole treatment decreases the antifungal activity of amphotericin B. This will likely be the case for newer, less toxic forms of the drug; but more studies need to confirm this. Two other drugs have also been shown to be active against azole-resistant Candidiasis. Voriconazole (Vfend) was recently approved in May of 2002 and showed enhanced activity against fluconazole-resistant candidiasis. Based on clinical trial data, dosage requirements are 200 mg twice daily or 3-6 mg/kg intravenously every 12 hours. Another drug called caspofungin acetate (Cancidas) has also shown activity against azole-resistant strains of candidiasis. Recommended dosage is 50 mg/day.
There are drug interactions that have been observed including with anti-HIV drugs, specifically efavirenz (Sustiva), nelfinavir (Viracept) and nevirapine (Viramune). The recommendation is to increase the daily dose to 70 mg if a person is taking any of these anti-HIV drugs.
Because of antifungal drug resistance, using drugs to prevent fungal infections is approached with great caution and is generally discouraged. For example, when fluconazole is used to prevent these infections and resistance develops, treating newer and more aggressive infections is difficult and often unsuccessful. So keeping the antifungal drugs for treatment is generally a more desirable approach. Some people with recurrent infections do remain on long-term therapy to prevent them. In this case, however, resistance still remains a concern.
|There are no known drug interactions for any topical treatment. The oral azole drugs have similar drug interactions.
Most nutritionists agree that sugar, yeast, dairy, wheat, caffeine, nicotine and alcohol are the main culprits because they help yeast to grow. To prevent this, they recommend eating as little as possible of these types of foods.
Another approach is to eat larger amounts of foods that may keep yeast from growing. For example, some nutritionists believe garlic has natural antifungal properties that may help prevent candidiasis. Fresh garlic is considered best, although commercial garlic "pills" help reduce the odors. Fresh garlic can be mixed into other foods, eaten raw (up to six cloves a day), or minced and put into empty gelatin capsules. (Note: It's unknown if large amounts of garlic interfere with anti-HIV therapies, but it may increase the risk of side effects from using ritonavir [Norvir].)
Another factor that can contribute to uncontrolled yeast growth is using antibiotics. "Friendly" bacteria are found naturally in the body and establish a healthy balance while eliminating unfriendly yeasts. Many common antibiotics, like tetracycline and penicillin, kill these bacteria which then allow yeast to grow, especially in the vagina. It is not unusual, even for people with healthy immune systems, to experience a fungal infection after using antibiotics.
In order to lessen this effect from antibiotics and promote healthy bacteria in general, many nutritionists recommend adding Lactobacilli acidophilus bacteria to your diet. It can be found in yogurts and certain milks (look for Lactobacilli acidophilus on the label). You can also take it in pill form, available at many health food stores.
Oral candidiasis can change how you taste and enjoy foods. It can also make eating and swallowing difficult. Avoiding acidic, spicy or hot foods as well as cigarettes, alcohol and carbonated drinks may help. All of these can irritate the insides of your mouth. Soft, cool and bland foods (like oatmeal, mashed beans, apple sauce, etc.) are recommended.
Liquid food supplements are often used to ease mouth infections and/or for weight maintenance. Remember supplements are not intended to replace solid foods. Many of these are high in sugars, which can help yeast grow. If you use supplements, make sure they contain mainly complex carbohydrates, are high in protein and have low-to-moderate sugar levels. For more information on food supplements, read Project Inform's publication, Maintaining Weight and Nutrition.
Overall, the best way to naturally prevent fungal infections is to eat healthfully and regularly, avoid excessive sugar intake and avoid or decrease alcohol and cigarettes.
|Oral (thrush), affects mouth and throat; usually occurs at CD4+ cell counts below 300||Discomfort, burning of mouth and throat; changed sense of taste; creamy white or yellowish patches on mouth or throat.||By appearance and symptoms. Lab tests are used if the infection does not clear after treatment.||Mouth rinses (nystatin, Mycostatin). Lozenges (nystatin, Mycostatin; clotrimazole, Mycelex). Capsules (fluconazole, Diflucan 100 mg/day or itraconazole, Sporanox 200 mg/day)||
Maintain good oral/dental hygiene. Avoid smoking and excess sugar.
|Vaginal (vaginitis, yeast infection), affects vagina and/or vulva||Odorous, white-yellow, creamy discharge with burning, swelling and itching.||By appearance and symptoms. Lab tests are used if the infection does not clear after treatment.||Vaginal creams or suppositories (clotrimazole or miconazole). Fluconazole oral tablets.||
Avoid douching and scented laundry soap, bleach and fabric softeners. Avoid washing vaginal area with deodorant soaps.
Wear loose fitting clothing and cotton underwear.
|Esophageal, affects the esophagus (feeding tube); usually occurs at CD4+ cell counts below 100||
Chest pain, nausea and painful swallowing.
Usually occurs with oral candidiasis.
|Examination of oropharnyx; endoscopy; culture and histology.||Ketoconazole (Nizoral) 200 or 400 mg/day or Fluconazole (Diflucan) at 200 mg once a day.||If more than one case has occurred, fluconazole preventive therapy may be warranted, particularly at low CD4+ cell counts.|
|Skin (usually affects skin in armpits, groin and under breasts)||Bright red, uneven eruption in the folds of skin that may be coated with a white membrane; mild burning feeling.||By appearance and symptoms. Lab tests are used if the infection does not clear after treatment.||Creams or ointments applied 2-4 times/day. Products include clotrimazole nystatin, ketoconazole, miconazole, econazole and amphotericin B.||Keep skin dry.|
|Systemic (affects organs throughout the body)||Can be difficult to diagnose.||Amphotericin B (Fungizone) orally or intravenously.|