DRUG REGIMENS FOR ADULTS AND ADOLESCENTS

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TABLE 2A. Prophylaxis for first episode of opportunistic disease in HIV-infected adults and adolescents

		Preventive regimens:
Pathogen	Indication	First choice	Alternatives
I. Strongly recommended as standard of care
Pneumocystis carinii*	CD4+ count <200/µL or oropharyngeal candidiasis or unexplained fever >2 weeks	Trimethoprim-sulfamethoxazole (TMP-SMZ), 1 DS po q.d. (AI); TMP-SMZ, 1 SS po q.d. (AI)	TMP-SMZ, 1 DS po t.i.w. (BIII); dapsone, 50 mg po b.i.d. or 100 mg po q.d. (BI); dapsone, 50 mg po q.d. plus pyrimethamine, 50 mg po q.w. plus leucovorin, 25 mg po q.w. (BI); dapsone, 200 mg po plus pyrimethamine, 75 mg po plus leucovorin, 25 mg po q.w. (BI); aerosolized pentamidine, 300 mg q.m. via Respirgard II™ nebulizer (BI)
Mycobacterium tuberculosis:
- Isoniazid-sensitive	TST reaction >5mm or prior positive TST result without treatment or contact with case of active tuberculosis	Isoniazid, 300 mg po plus pyridoxine, 50 mg po q.d. x 12 mo (AI) or isoniazid, 900 mg po plus pyridoxine, 50 mg po b.i.w. x 12 mo (BIII)	Rifampin, 600 mg po q.d. x 12 mo (BII)
- Isoniazid-resistant	Same; high probability of exposure to isoniazid-resistant tuberculosis	Rifampin, 600 mg po q.d. x 12 mo (BII)	Rifabutin, 300 mg po q.d. x 12 mo (CIII)
- Multidrug- (isoniazid and rifampin) resistant	Same; high probability of exposure to multidrug-resistant tuberculosis	Choice of drugs requires consultation with public health authorities	None
Toxoplasma gondii §	IgG antibody to Toxoplasma and CD4+ count <100/µL	TMP-SMZ, 1 DS po q.d. (AII)	TMP-SMZ, 1 SS po q.d. (BIII): dapsone, 50 mg po q.d. plus pyrimethamine, 50 mg po q.w. plus leucovorin, 25 mg po q.w. (BI)
Mycobacterium avium complex ¶	CD4+ count <50µL	Clarithromycin, 500 mg po b.i.d. (AI) or azithromycin, b.i.d. 1,200 mg po q.w. (AI)	Rifabutin, 300 mg po q.d. (BI); azithromycin, 1,200 mg po q.w. plus rifabutin, 300 mg po q.d. (CI)
Streptococcus pneumoniae**	All patients	Pneumococcal vaccine, 0.5 mL im x 1 (CD4+ >200/µL [All]; CD4+ <200/µL [CIII])	None
Varicella zoster virus (VZV)	Significant exposure to chickenpox or shingles for patients who have no history of either condition or, if available, negative antibody to VZV	Varicella zoster immune globulin (VZIG), 5 vials (1.25 mL each) im, administered <96 h after exposure, ideally within 48 h (AIII)	Acyclovir, 800 mg po 5 times/d for 3 weeks (CIII)
II. Generally recommended
Hepatitis B virus	All susceptible (anti-HBc-negative) patients	Engerix B® NOTE: , 20 mg imx 3 (BII); or Recombivax HB® NOTE: , 10 µg imx 3 (BII)	None
Influenza virus	All patients (annually, before influenza season)	Whole or split virus, 0.5 mL im/yr (BIII)	Rimantadine, 100 mg po b.i.d. (CIII) or amantadine, 100 mg po b.i.d. (CIII)
III. Not recommended for most patients; indicated for use only in unusual circumstances:
Candida species	CD4+ count <50/µL	Fluconazole, 100–200 mg po q.d. (CI)
Bacteria	Neutropenia	Granulocyte-colony–stimulating factor (G-CSF), 5–10 µg/kg sc q.d. x 2–4w or granulocyte-macrophage colony-stimulating factor (GM-CSF), 250 mg/m2 iv over 2 h q.d. x 2–4w (CIII)
Cryptococcus neoformans §§	CD4+ count <50/µL	Fluconazole, 100–200 mg po	Itraconazole, 200 mg po q.d. (CIII)
Histoplasma capsulatum §§	CD4+ count <100/µL, endemic geographic	Itraconazole, 200 mg po q.d. (CI)	None
Cytomegalovirus (CMV) ¶¶	CD4+ count <50/µL and CMV antibody positivity	Oral ganciclovir, 1 g po t.i.d. (CI)	None

NOTE: Information included in these guidelines may not represent Food and Drug Administration (FDA) approval or approved labeling for the particular products or indications in question. Specifically, the terms "safe" and "effective" may not be synonymous with the FDA-defined legal standards for product approval. Anti-HBc = antibody to hepatitis B core antigen; b.i.w. = twice a week; CMV = cytomegalovirus; DS = double-strength tablet; q.m. = monthly; q.w. = weekly; SS = single-strength tablet; t.i.w. = three times a week; TMP-SMZ = trimethoprim-sulfamethoxazole; and TST = tuberculin skin test.


The Respirgard II™ nebulizer is manufactured by Marquest, Englewood, CO.
Engerix-B® NOTE: by SmithKline Beecham.
Rixensart, Belgium; and Recombivax HB® NOTE: by Merck & Co., West Point, PA.
Letters and Roman numerals in parentheses after regimens indicate the strength of the recommendation and the quality of evidence supporting it (see text).


* Patients receiving dapsone should be tested for glucose-6 phosphate dehydrogenase deficiency. A dosage of 50 mg q.d. is probably less effective than that of 100 mg q.d. The efficacy of parenteral pentamidine (e.g., 4 mg/kg/month) is uncertain. Inadequate data are available regarding efficacy or safety of atovaquone or clindamycin-primaquine. Fansidar (sulfadoxine-pyrimethamine) is rarely used because of severe hypersensitivity reactions. TMP-SMZ reduces the frequency of some bacterial infections. Patients who are being administered therapy for toxoplasmosis with sulfadiazine-pyrimethamine are protected against Pneumocystis carinii pneumonia and do not need TMP-SMZ.


Directly observed therapy required for isoniazid (INH), 900 mg b.i.w.; INH regimens should include pyridoxine to prevent peripheral neuropathy. Rifampin should not be administered concurrently with protease inhibitors (20). Rifabutin, which may be administered at a reduced dose with indinavir or nelfinavir, is an option; consult an expert. Exposure to multidrug-resistant tuberculosis may require prophylaxis with two drugs; consult public health authorities. Possible regimens include pyrazinamide plus either ethambutol or a fluoroquinolone (21).

§ Protection against Toxoplasma is provided by the preferred anti- Pneumocystis regimens. Pyrimethamine alone probably provides little, if any, protection.

¶ Rifabutin should not be administered concurrently with the protease inhibitors saquinavir or ritonavir; however, it may be administered at half the dose (150 mg q.d.) with indinavir or nelfinavir.

** Vaccination should be offered to persons who have a CD4+ T-lymphocyte count <200 cells/µL, although the efficacy may be diminished. Some authorities are concerned that immunizations may stimulate the replication of HIV. However, one study showed no adverse effect of pneumococcal vaccination on patient survival (22). Revaccination >5 years after the first dose is considered optional.

These immunizations or chemoprophylactic regimens do not target pathogens traditionally classified as opportunistic but should be considered for use in HIV-infected patients. Data are inadequate concerning clinical benefit of these vaccines in this population, although it is logical to assume that those patients who develop antibody responses will derive some protection. Some authorities are concerned that immunizations may stimulate HIV replication, although, for influenza vaccination, a large observational study of HIV-infected persons in clinical care showed no adverse effect of this vaccine, including multiple doses, on patient survival (J. Ward, CDC, personal communication). Hepatitis B vaccine has been recommended for all children and adolescents and for all adults with risk factors for hepatitis B infection ( 23 ). Rimantadine/amantadine are appropriate during outbreaks of influenza A. For additional information regarding vaccination against hepatitis B and vaccination and antiviral therapy against influenza, see references 23 and 24. Because of the theoretical concern that increases in HIV plasma RNA following vaccination during pregnancy might increase the risk of perinatal transmission of HIV, providers may wish to defer vaccination until after antiretroviral therapy is initiated.

§§ There may be a few unusual occupational or other circumstances under which to consider prophylaxis; consult a specialist.

¶¶ Acyclovir is not protective against CMV. Valaciclovir is not recommended because of an unexplained trend toward increased mortality observed in persons who have AIDS who were being administered this drug for prevention of CMV disease.

TABLE 2B. Prophylaxis for recurrence of opportunistic disease (after chemotherapy for acute disease) in HIV-infected adults and adolescents

		Preventive regimens:
Pathogen	Indication	First choice	Alternatives
I. Strongly recommended as standard of care
Pneumocystis carinii	Prior P. carinii pneumonia	Trimethoprim-sulfamethoxazole (TMP-SMZ), 1 DS po q.d. (AI); TMP-SMZ 1 SS po q.d. (AI)	TMP-SMZ, 1 DS po t.i.w.. (CIII); dapsone, 50 mg po b.i.d. or 100 mg po q.d. (BI); dapsone, 50 mg po q.d. plus pyrimethamine, 50 mg po q.w. plus leucovorin, 25 mg po q.w. (BI); dapsone, 200 mg po plus pyrimethamine, 75 mg po plus leucovorin, 25 mg po q.w. (BI); aerosolized pentamidine, 300 mg q.m. via Respirgard II™ nebulizer (BI)
Toxoplasma gondii*	Prior toxoplasmic encephalitis	Sulfadiazine 500–1000 mg po q.i.d. plus pyrimethamine 25–75 mg po q.d. plus leucovorin 10 mg po q.d. (AI)	Clindamycin, 300–450 mg po q 6-8 h plus pyrimethamine, 25–75 mg po q.d. plus leucovorin, 10–25 mg po q.d.-q.i.d. (BI)
Mycobacterium avium complex	Documented disseminated disease	Clarithromycin, 500 mg po b.i.d. (AI) plus one or more of the following: ethambutol, 15 mg/kg po q.d. (AII); rifabutin, 300 mg po q.d. (AII)	Azithromycin, 500 mg po q.d. (AII) plus one or more of the following: ethambutol, 15 mg/kg po q.d. (AII); rifabutin, 300 mg po q.d. (AII)
Cytomegalovirus	Prior end-organ disease	Ganciclovir, 5–6 mg/kg IV 5–7 days/wk or 1,000 mg po t.i.d. (AI); or foscarnet, 90–120 mg/kg iv q.d. (AI); or cidofovir, 5 mg/kg IV q.o.w. (AI); or (for retinitis) ganciclovir sustained-release implant q 6–9 months (AI)
Cryptococcus neoformans	Documented disease	Fluconazole, 200 mg po q.d. (AI)	Amphotericin B, 0.6–1.0 mg/kg IV q.w.–t.i.w. (AI); itraconazole, 200 mg po q.d. (BI)
Histoplasma capsulatum	Documented disease	Itraconazole, 200 mg po b.i.d. (AII)	Amphotericin B, 1.0 mg/kg IV q.w. (AII); fluconazole, 400 mg po q.d. (CII)
Coccidioides immitis	Documented disease	Fluconazole, 400 mg po q.d. (AII)	Amphotericin B, 1.0 mg/kg IV q.w. (AI); itraconazole, 200 mg po b.i.d. (AII)
Salmonella species (non-typhi) §	Bacteremia	Ciprofloxacin, 500 mg po b.i.d. for several months (BII)	None
II. Recommended only if subsequent episodes are frequent or severe
Herpes simplex virus	Frequent/severe recurrences	Acyclovir, 200 mg po t.i.d. or 400 mg po b.i.d. (AI)
Candida (oral, vaginal, or esophageal)	Frequent/severe recurrences	Fluconazole, 100–200 mg po q.d. (AI)	Ketoconazole, 200 mg po q.d. (CIII); itraconazole, 200 mg po q.d. (CIII)

NOTE: Information included in these guidelines may not represent Food and Drug Administration (FDA) approval or approved labeling for the particular products or indications in question. Specifically, the terms "safe" and "effective" may not be synonymous with the FDA-defined legal standards for product approval. DS = double-strength tablet; q.m. = monthly; q.w. = weekly; SS = single-strength tablet; t.i.w. = three times a week; and TMP-SMZ = trimethoprim-sulfamethoxazole.

The Respirgard II™ nebulizer is manufactured by Marquest, Englewood, CO.

Letters and Roman numerals in parentheses after regimens indicate the strength of the recommendation and the quality of the evidence supporting it (see text).

*Pyrimethamine/sulfadiazine confers protection against PCP as well as toxoplasmosis; clindamycin-pyrimethamine does not.

Æ Many multiple-drug regimens are poorly tolerated. Drug interactions (e.g., those seen with clarithromycin/ rifabutin) can be problematic; rifabutin has been associated with uveitis, especially when administered at daily doses of >300 mg or concurrently with fluconazole or clarithromycin. Rifabutin should not be administered concurrently with the protease inhibitors saquinavir or ritonavir, but it can be administered at half dose (150 mg q.d.) with indinavir or nelfinavir.

§ The efficacy of eradication of Salmonella has been demonstrated only for ciprofloxacin.

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