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Opportunistic Infections Update

September 1999

The US Public Health Service and the Infectious Disease Society of America recently issued new guidelines for the prevention of opportunistic infections (OIs). The revised guidelines take into account the increasingly common practice of stopping preventive treatment (to reduce the risk of getting a particular infection) and maintenance therapies (to prevent relapse) when someone has sustained CD4+ cell count increases as a result of highly active anti-HIV therapy.

While there have been few new therapies for treating or preventing OIs, most advances in this field come from a developing knowledge of how best to use existing anti-OI therapies -- in short, better strategies using current drugs. The revised guidelines include recommendations on when to start preventive therapy, recommendations for maintenance therapies and guidance for stopping preventive or maintenance therapies. The chart below provides the guidelines for the prevention of opportunistic infections.

It is important to consider the potential for drug interactions when planning to use preventive and maintenance therapies. For more information on drug interactions, call Project Inform's National HIV/AIDS Treatment Hotline and ask for the Drug Interactions Chart.

Candidiasis
Cryptococcosis
Cryptosporidiosis
Cytomegalovirus (CMV)
Histoplasmosis
Mycobacterium Avium Complex (MAC)
Pneumocystis carinii Pneumonia (PCP)
Toxoplasmosis
Tuberculosis

 

Candidiasis:
A fungus (yeast) that can infect the mouth and throat (thrush) and/or vagina. May result in white patches, loss of appetite and/or vaginal itching, burning and discharge.
When to Start Preventive Therapy 3 Routine preventive therapy is not recommended because of the potential for developing untreatable, drug-resistant candida.

Recommended Preventive Therapies

  • Although routine prevention is not recommended, studies have shown that fluconazole (Diflucan®) reduces the risk of developing candidiasis.
  • Pregnant women should not use preventive therapies, particularly "azole" drugs, due to risk of birth defects.
Stopping Preventive
Therapy 1
 
Who Should Use
Maintenance Therapy
  • Many experts do not recommend maintenance therapy for the same reasons preventive therapy is not recommended. If recurrences are frequent or severe, then fluconazole or itraconazole solution (Sporanox®) can be considered.
  • Pregnant women should avoid "azole" drugs and opt for topical therapies or in severe cases, amphotericin B (Fungizone®).
Stopping Maintenance
Therapy 1
 

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Cryptococcosis:
A fungus that primarily infects the brain resulting in headaches, fevers and altered behavior.
When to Start Preventive Therapy 3
  • Many experts do not recommend prevention because of the low overall incidence of the disease and lack of proven benefit.
  • If a need for prevention of other fungal infections exists then people with CD4+ cell counts below 50 should consider preventive therapies.

Recommended Preventive Therapies

  • Fluconazole is the preferred therapy.
  • Pregnant women should not use "azole" drugs for prevention because of possible birth defects. Also, women who become pregnant should stop any "azole" antifungal therapies.
Stopping Preventive
Therapy 1
 
Who Should Use
Maintenance Therapy
  • Everyone who has had cryptococcal disease should be on maintenance therapy for life. Fluconazole is the preferred therapy for maintenance therapy.
  • Pregnant women should avoid "azole" drugs.
Stopping Maintenance
Therapy 1
Based on the small numbers of people studied, stopping therapy is not currently recommended.

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Cryptosporidiosis:
A parasitic infection that can cause diarrhea.
When to Start Preventive Therapy 3 The greatest risk is for people with CD4+ cell counts below 100.

Recommended Preventive Therapies

No proven effective therapies against cryptosporidiosis exist. People should try to avoid exposure to the organism which sometimes has been found in public water supplies. 3
Stopping Preventive
Therapy 1
 
Who Should Use
Maintenance Therapy
 
Stopping Maintenance
Therapy 1
 

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Cytomegalovirus (CMV):
A virus that can infect the entire body. Left untreated, CMV can cause diarrhea, blindness, inflammation of the brain, among other things. Most common is infection of the eye (retina), CMV retinitis.
When to Start Preventive Therapy 3 People whose CD4+ cell counts stay consistently below 50 and who are CMV+ are at highest risk for CMV infection and should consider CMV prevention.

Recommended Preventive Therapies

  • Oral ganciclovir (Cytovene®) is the recommended preventive therapy.
  • Pregnant women should not take preventive therapies. Also, women who become pregnant should stop oral ganciclovir preventive therapy because of possible birth defects.
Stopping Preventive
Therapy 1
It may be reasonable for people with a sustained (six months or longer) CD4+ cell count above 100-150 as a result of HAART to consider stopping CMV prevention.
Who Should Use
Maintenance Therapy
  • People with a history of active CMV disease should be on maintenance therapy for life. Oral or intravenous (IV) ganciclovir, IV cidofovir (Vistide®), IV foscarnet (Foscavir®), IV foscarnet + IV ganciclovir or ganciclovir implants (Vitrasert®) (for retinitis only) are recommended.
  • Pregnant women should receive maintenance therapy and the choice of therapy should be individualized.
Stopping Maintenance
Therapy 1

It may be reasonable for people with CD4+ cell counts sustained above 100-150 AND sustained suppression of viral load to consider stopping CMV main-tenance therapy. Immune recovery uveitis (IRU), a potentially sight-threatening inflammation, has been observed in some people who have discontinued maintenance therapy. This should be monitored.

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Histoplasmosis:
A fungus that can cause fevers, fatigue and difficulty breathing. Common only in a few areas of the country, primarily midwestern river valleys.
When to Start Preventive Therapy 3 People whose CD4+ counts stay consistently below 100 and who live in an area where histoplasma is commonly found.

Recommended Preventive Therapies

  • Itraconazole is the preferred therapy.
  • Pregnant women should not receive prevention because of possible birth defects associated with "azole" drugs.
Stopping Preventive
Therapy 1
No recommendation at this time.
Who Should Use
Maintenance Therapy
  • Everyone who has had histoplasmosis should be on maintenance therapy for life. Itraconazole is the preferred maintenance therapy.
  • For pregnant women, amphotericin B (Fungizone®) is preferred, especially during the first trimester of pregnancy.
Stopping Maintenance
Therapy 1

Based on the small numbers of people studied, stopping therapy is not currently recommended.

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Mycobacterium Avium Complex (MAC):
A bacterial infection that can cause fever, night sweats, fatigue, anemia and diarrhea.
When to Start Preventive Therapy 3
  • People whose CD4+ count stays consistently below 50.
  • Pregnant women may want to consider delaying prevention until after the first trimester of pregnancy.

Recommended Preventive Therapies

  • Clarithromycin (Biaxin®) or azithromycin (Zithromax®) are the preferred preventive therapies. If someone cannot tolerate either drug, then rifabutin is the recommended alternative.
  • For pregnant women, azithromycin is the drug of choice. Clarithromycin should be used with caution in pregnant women because of birth defects in animal studies.
Stopping Preventive
Therapy 1

It may be reasonable for people with CD4+ cell counts sustained above 100 for 3-6 months AND sustained viral load suppression to consider stopping MAC preventive therapy.

Who Should Use
Maintenance Therapy
Everyone who has had MAC should be on maintenance therapy for life with either clarithromycin or azithromycin (only if it has been proven that there is no resistance to either of these drugs) in combination with ethambutol (Myambutol®) with or without rifabutin.
Stopping Maintenance
Therapy 1

It may be reasonable for people with CD4+ cell counts sustained above 100 for 6-12 months as a result of HAART to consider stopping MAC maintenance therapy.

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Pneumocystis carinii Pneumonia (PCP):
An infection that can cause fever, dry cough, difficulty breathing, weight loss and night sweats.
When to Start Preventive Therapy 3
  • People who have CD4+ cell counts below 200 or a history of thrush (candidiasis) in the mouth and throat should receive PCP preventive therapy.
  • People with CD4+ percentages below 14% or a prior AIDS-defining illness should consider starting preventive therapy.
  • If it is not possible to monitor CD4+ cell counts every three months, then people with counts below 250 should consider starting prevention.
  • Pregnant women may want to consider delaying prevention until after the first trimester of pregnancy.

Recommended Preventive Therapies

  • One double-strength TMP-SMX (Bactrim®, Septra®) per day is recommended, although one double-strength tablet three times a week or one single-strength tablet a day is also effective.
  • People with allergic reactions (fever and/or rash) may be able to desensitize to the drug. 2 If someone cannot tolerate TMP-SMX, then dapsone; dapsone + pyrimethamine (Daraprim®) + leucovorin; aerosolized pentamidine (Pentam®); or atovaquone (Mepron®) are alternatives.
Stopping Preventive
Therapy 1
It may be safe for people with sustained (six months or longer) CD4+ cell counts above 200, as a result of HAART, to consider stopping preventive therapy.
Who Should Use
Maintenance Therapy
People with a history of PCP should use the same therapies as those recommended for prevention.
Stopping Maintenance
Therapy 1
It may be possible for people to stop maintenance therapy if CD4+ cell counts increase and stay over 200. However, based on the small numbers of people studied, this is not currently recommended.

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Toxoplasmosis:
A parasite that primarily infects the brain resulting in confusion and delusional behavior.
When to Start Preventive Therapy 3
  • People with CD4+ cell counts below 100 if toxoplasma antibody positive.
  • Pregnant women may want to consider delaying a pyrimethamine-containing regimen until after pregnancy.

Recommended Preventive Therapies

Daily doses of TMP-SMX is the preferred therapy. If someone cannot tolerate TMP-SMX, then dapsone + pyrimethamine or atovaquone +/- pyrimethamine are alternatives.
Stopping Preventive
Therapy 1
It may be possible to stop prevention if CD4+ counts remain above 100 as a result of HAART for six months or longer. Based on the small numbers studied, this is not yet recommended.
Who Should Use
Maintenance Therapy

People with a history of toxoplasmosis should use a combination of sulfadiazine + pyrimethamine For people intolerant to sulfa drugs (e.g. TMP-SMX or sulfadiazine), a combination of pyrimethamine + clindamycin is an alternative.

Stopping Maintenance
Therapy 1
Based on the small numbers of people studied, stopping maintenance therapy is not currently recommended.

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Tuberculosis (TB):
A bacterium that primarily infects the lungs and can cause cough, weight loss and fatigue. TB is easily spread to others.
When to Start Preventive Therapy 3
  • Everyone with HIV may be at increased risk and should be tested for exposure to tuberculosis, generally with a tuberculin skin test (TST).
  • When TST is positive but there is no active disease, a preventive course of therapy should be initiated.
  • Pregnant women with no active disease may consider delaying preventive therapy until after the first trimester.
  • When TST positive and active disease is present, initiate anti-TB treatment.

Recommended Preventive Therapies

  • TST positive people without signs of active TB, should receive nine months of isoniazid (INH) once daily or twice weekly or two months of pyrazinamide with either rifampin (Rifadin®) or rifabutin (Mycobutin®). If someone comes into close contact with a person with active TB, they should also receive the above mentioned regimen.
  • Pyrazinamide should be avoided during the first trimester of pregnancy due to known risks to the developing baby.
Stopping Preventive
Therapy 1

Not recommended.

Who Should Use
Maintenance Therapy
Maintenance therapy is not required for people successfully completing a TB treatment regimen.
Stopping Maintenance
Therapy 1
Not applicable.

1 Before stopping any maintenance or preventive therapies it is important to discuss this with a doctor.
2 Call the Project Inform Hotline for a PCP Prevention Fact Sheet for a desensitization regimen.
3 Call the Project Inform Hotline and ask for WISE Words #4 for ways to prevent exposure to common infections.


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