The quality of evidence (I-III) is defined at the end of the "Major Recommendations" field.
Pneumocystis jirovecii (PCP)
Presentation
Clinicians should place all hospitalized human immunodeficiency virus (HIV)-infected patients with respiratory symptoms and/or abnormal chest x-rays in respiratory isolation in a negative pressure room until active pulmonary tuberculosis is excluded or an alternative diagnosis that accounts for the abnormalities is established. (I)
Diagnosis
Clinicians should obtain evidence of the characteristic organisms in induced sputum, bronchoalveolar lavage fluid, or tissue specimen. (III)
Clinicians should obtain a bronchoalveolar lavage if induced sputum is negative or unavailable. (III)
Treatment
Clinicians should treat PCP with trimethoprim/sulfamethoxazole (TMP/SMX) administered either parenterally or orally, depending on the severity of the illness and likelihood of adherence. A total of 21 days of therapy should be completed. Dosing regimens and alternative drugs are listed in the table below. (I)
Clinicians should hospitalize patients with severe disease, as defined by initial room air pO2 of <70 mm Hg or an arterial-alveolar oxygen gradient of >35 mm Hg, and administer parenteral treatment with the most effective agent and steroids. (I)
If PCP fails to improve within 7 to 10 days of treatment, clinicians should consider an alternative diagnosis and a change in PCP therapy, generally from trimethoprim/sulfamethoxazole to intravenously administered pentamidine. (II)
Clinicians should administer adjunctive steroids to persons with PCP who have significant hypoxia (see table below). (I)
Clinicians should initiate secondary prophylaxis to prevent recurrence of PCP immediately after completion of the treatment regimen. (II)
Table
Treatment of PCP in HIV-Infected Individuals
Clinical Status |
Preferred Regimen |
Alternatives |
Patient acutely ill
pO2 <70 mmHg
or
A-a gradient >35 mmHg
|
TMP/SMX: 15 to 20 mg/kg* intravenously (IV), based on TMP, divided every 6 hours (q6h)or every 8 hours (q8h)
plus
Prednisone:
40 mg orally (PO) twice a day (bid), days 1-5
40 mg PO once a day (qd), days 6-10
20 mg PO qd, days 11-21
|
- Pentamidine isethionate:
3 to 4 mg/kg/day IV, infused over 90 minutes
plus
Prednisone as in the preferred regimen
or
- Clindamycin: 900 mg IV q8h**
plus
Primaquine base: 15 to 30 mg PO qd
plus
Prednisone as in the preferred regimen
|
Patient able to take medication orally
pO2 ≥70 mmHg
or
A-a gradient ≤35 mmHg
|
TMP/SMX: 15 to 20 mg/kg four times a day (qid) based on weight |
- Dapsone: 100 mg PO qd***
plus
TMP: 5 mg/kg three times a day (tid)
or
- Clindamycin: 450 mg PO q8h
plus
Primaquine: 15 mg base PO qd
or
- Atovaquone suspension: 750 mg PO bid (with a fatty meal to maximize absorption)
|
* The dose of 15 mg /kg is as effective as the dose of 20 mg/kg and has less hematological toxicity.
** The efficacy of clindamycin has not been established for the treatment of severe disease.
*** Check glucose-6 phosphate dehydrogenase (G6PD) screen prior to initiation. Hemolytic anemia may occur in some cases of G6PD deficiency.
Prevention
Clinicians should initiate PCP prophylaxis in patients with CD4 cell counts <200 cells/mm3, or ≤14% of total lymphocytes, and in patients with higher CD4 counts who have a history of PCP, thrush, or unexplained constitutional symptoms of >2 weeks' duration (I). TMP/SMX is the referred prophylactic agent for PCP (I). See the table below for specific recommendations.
Clinicians should discontinue primary and secondary PCP prophylaxis when patients have responded to highly active antiretroviral therapy (HAART) with a sustained CD4 cell count of ≥200 cells/mm3 for ≥3 months. (I)
Table
Prophylactic Regimens for PCP
Drug |
Dose |
TMP/SMX* (preferred) |
1 DS tablet daily**
or
1 SS tablet daily
or
1 DS tablet three times/week
|
Dapsone*** |
100 mg PO qd
or
50 mg PO daily
plus
pyrimethamine 50 mg weekly plus leucovorin 25 mg PO weekly#
or
200 mg plus pyrimethamine 75 mg plus leucovorin 25 mg weekly
|
Atovaquone¶ |
1500 mg PO qd (or 750 mg bid) |
Pentamidine isethionate (aerosolized pentamidine) |
300 mg in 6 cc sterile water via Respirgard II nebulizer once a month |
DS, double strength; SS, single strength.
* There is an increased risk of prophylaxis failure with advancing immunosuppression, especially for non-TMP/SMX regimens.
** 1 DS tablet TMP/SMX is effective for prophylaxis against toxoplasmosis as well. Lower doses might also provide such protection.
*** Exclude G6PD deficiency before initiating. Hemolytic anemia may occur in some cases of G6PD deficiency.
# This regimen is effective prophylaxis against toxoplasmosis in individuals who are intolerant to TMP/SMX.
¶ Results from CPCRA/ACTG 277 showed that atovaquone in suspension, at the dose of 1500 mg PO daily is comparable to dapsone for PCP prophylaxis. No overall differences in the rate of adverse effects were noted in this study. Although some patients may better tolerate dapsone, the relative risk for discontinuation was greater with this agent than with atovaquone. Atovaquone is significantly more expensive.
Toxoplasma gondii
Diagnosis
Although the definitive diagnosis of toxoplasma encephalitis requires a brain biopsy, clinicians should use the following presumptive criteria to diagnose cerebral toxoplasmosis (II):
- Multiple ring-enhancing central nervous system mass lesions demonstrated by an imaging study; magnetic resonance imaging (MRI) is more sensitive than a contrast-enhanced computed tomography (CT) scan
- Positive serum immunoglobulin G (IgG) to T. gondii
- CD4 count <100 cells/mm3
- Lack of toxoplasmosis prophylaxis
Clinicians should consider alternative diagnoses if there is an absence of serum IgG antibodies to T. gondii. (III)
Clinicians should obtain a brain biopsy to establish a definitive diagnosis if the patient fails to clinically and radiographically respond to therapy within 10 to 14 days or the presentation is unusual enough to make the diagnosis uncertain. (III)
Treatment
Clinicians should continue acute therapy for toxoplasmosis until there is clinical improvement and radiographic evidence of reduction in size and number of lesions (for 4 to 6 weeks) and should follow with suppressive therapy. (III)
Table
Treatment of Acute Toxoplasmosis in HIV-Infected Patients
Preferred Regimen |
Alternative |
Sulfadiazine 1-1.5 g PO every six hours (q6h)
plus
Pyrimethamine 200 mg PO loading dose followed by 50-100 mg PO qd
plus
Leucovorin 10-20 mg PO qd
|
- Clindamycin 600-1200 mg IV every 12 hr
plus
Pyrimethamine 200 mg PO loading dose followed by 50-100 mg PO qd
plus
Leucovorin 10-20 mg PO qd
or
- Pyrimethamine 200 mg PO loading dose followed by 50-100 mg PO qd
plus
Leucovorin 10-20 mg PO qd
plus
Azithromycin 1200-1500 mg/day
or
Clarithromycin 500-1000 mg/day
or
Atovaquone 750 mg qid
|
Table
Prevention of Recurrent Toxoplasmosis in HIV-Infected Patients
Preferred Regimen |
Alternative |
Sulfadiazine 1 g PO bid
plus
Pyrimethamine 50 mg PO qd
plus
Leucovorin 10 mg PO qd
|
- Clindamycin 300 mg PO q6h
plus
Pyrimethamine 50 mg PO qd
plus
Leucovorin 10 mg PO qd
- Sulfadiazine 1 g PO bid
plus
Pyrimethamine 50 mg PO
plus
Leucovorin 10 mg PO
Entire regimen given thrice weekly
- Atovaquone 750 mg bid or qid
|
Prevention
Clinicians should initiate prophylaxis for toxoplasmosis when a patient's CD4 count decreases to <100 cells/mm3 and the patient is toxoplasma IgG positive (I). TMP/SMX is the preferred prophylactic agent for toxoplasmosis (I). (Refer to table below).
Clinicians should discontinue primary toxoplasmosis prophylaxis when patients have responded to HAART with a sustained (≥3 months) increase in CD4 cell count (>200 cells/mm3). (I)
Clinicians should counsel HIV-infected toxoplasma-seronegative patients to avoid undercooked meats and to carefully wash hands after handling cat litter boxes and after gardening. (III)
Table
Toxoplasmosis Prophylaxis Regimens in HIV-Infected Patients
Medication |
Dose
|
TMP/SMX |
1 DS PO daily (preferred)
or
1 SS PO daily
|
Dapsone*
plus
Pyrimethamine
plus
Leucovorin
|
50 mg PO daily
50 mg PO weekly
25 mg PO weekly
|
Dapsone*
plus
Pyrimethamine
plus
Leucovorin
|
200 mg weekly
75 mg weekly
25 mg weekly
|
Atovaquone |
1500 mg once a day |
DS, double strength; SS, single strength.
* Exclude G6PD deficiency before initiating.
Cryptosporidiosis
Presentation
Clinicians should include cryptosporidiosis in the differential diagnosis of diarrhea, especially large-volume diarrhea. (I)
Diagnosis
Clinicians should specifically request acid-fast staining or immunofluorescent antibody testing of the stool to establish a diagnosis of cryptosporidiosis. (I)
Clinicians should specifically alert the laboratory to look for cryptosporidia if this diagnosis is suspected (III).
Treatment
Clinicians should prescribe a combination of paromomycin 1 g twice a day (bid) plus azithromycin 600 mg orally (PO) daily for 4 weeks, followed by paromomycin maintenance therapy. (III)
Prevention
Clinicians should counsel patients to:
- Avoid contact with human and animal feces, pets with diarrhea, dogs or cats <6 months of age
- Avoid drinking water from lakes, streams, or rivers, unless it has been adequately boiled
- Boil water for 1 minute when public health agencies issue a boil-water advisory during waterborne outbreaks of cryptosporidiosis
Isospora belli
Diagnosis
Because Isospora belli is shed intermittently in the stool, clinicians should request multiple stool specimens for modified acid-fast stool staining. (I)
Treatment
Clinicians should treat Isospora belli with TMP/SMX double strength (DS) PO four times daily for at least 10 days. (I)
Clinicians should consider using pyrimethamine 50 to 75 mg/day for 10 days in patients allergic to sulfa, followed by leucovorin 5 to 10 mg/day. (III)
Clinicians should consider discontinuing isosporiasis prophylaxis for patients who are asymptomatic and have sustained CD4 >200 cells/mm3 for ≥3 months. (III)
Cyclospora
Diagnosis
Clinicians should base the diagnosis of cyclosporiasis on microscopic detection of oocysts in stool. (I)
Treatment
Clinicians should prescribe oral TMP/SMX 160 mg/800 mg four times a day for 10 days, followed by secondary prophylaxis with TMP/SMX three times a week to treat Cyclospora infection in HIV-infected patients. (I)
Giardia
Treatment
Clinicians should treat Giardia with metronidazole 250 mg PO three times a day (tid) for 5 to 10 days. (I)
Clinicians should educate Giardia-infected patients regarding improved hygienic measures. (III)
Amebiasis
Diagnosis
Clinicians should obtain at least three stool specimens before excluding the diagnosis of amebiasis. (II)
Treatment
Clinicians should initiate treatment of Entamoeba histolytica when trophozoites with ingested red blood cells are present in the stool. One of the following regimens should be used (II):
- Metronidazole 750 mg tid for 10 days or 2.4 g daily (qd) for 3 days
- Tinidazole 2 g PO qd for 3 days followed by paromomycin 500 mg tid for 7 days
- Iodoquinol 650 mg tid for 20 days
Clinicians should treat patients with asymptomatic E. histolytica infection with one of the following regimens (II):
- Paromomycin 500 mg tid for 7 days
- Iodoquinol 650 mg tid for 20 days
- Diloxanide furoate 500 mg tid for 10 days
Clinicians should treat extraintestinal disease with metronidazole 750 mg tid for 10 days or 2.4 g qd for 3 days (II).
Definitions:
Quality of Evidence for Recommendation
- Evidence from one or more properly randomized, controlled trial
- Evidence from one or more well-designed clinical trial without randomization; from cohort or case-controlled studies
- Evidence from opinions of respected authorities based on clinical experience, descriptive studies, or reports of expert committees