Johns Hopkins AIDS Service

Opportunistic Infection Prophylaxis Update

By Richard E. Chaisson, M.D.

July 1996

Prevention of opportunistic infections remains a critically important management strategy for patients with HIV disease. Guidelines published last year by the US Public Health Service/Infectious Disease Society of America Working Group categorized prophylaxis options into three groups. Category I are those treatments recognized as the standard of care for all eligible patients; in other words, not to use these treatments constitutes a breach of professional standards. Category II includes treatments that should be strongly considered for all eligible patients, but not to offer these therapies would not constitute substandard care. Category III includes treatments that may be considered for selected patients, but there is no mandate to use or even consider these options as standard therapies. The major considerations that led to the categorizations were incidence of disease, efficacy of prophylaxis, impact on survival and cost.

Since publication of these guidelines there have been two important advances in prophylaxis. First, prophylaxis for Mycobacterium avium complex (MAC) has been shown to prolong survival, and the macrolides clarithromycin and azithromycin have been found to be superior to rifabutin. Most authorities now agree that prophylaxis of MAC for patients with CD4 counts <75 should be the standard of care. Second, prophylaxis of CMV disease with oral ganciclovir has been shown to be highly efficacious, with a 50 percent reduction in the risk of retinitis and other serious forms of CMV disease. Oral ganciclovir did not significantly prolong survival, and the dosage form (12 pills per day) and cost of this therapy (~$14,000 per year) make its routine use problematic. Most experts now agree, however, that CMV prophylaxis should be considered for patients who are CMV seropositive and have CD4 counts <50. Use of CMV DNA PCR assays may help further target patients at high risk of CMV disease.

Below is an updated summary of the USPHS/IDSA guidelines, with alternatives for the first line treatments. It is likely that this document will be amended to make MAC a Category I disease and CMV a Category II disease.

Tables are reprinted from Chaisson, RE, 6th Annual Clinical Care Options for HIV Symposium, Opportunistic Infections: Impact on the Natural History of HIV Infection. May 2-5, 1996, Section 5. Adapted from MMWR 1995; 44(RR-8):1-10.

Table 1
PROPHYLAXIS OF FIRST EPISODE OF OPPORTUNISTIC DISEASES IN HIV-INFECTED ADULTS: STRONGLY RECOMMENDED AS STANDARD OF CARE
		PREVENTIVE REGIMENS
PATHOGEN	INDICATION	FIRST CHOICE	ALTERNATIVES
Pneumocystis carinii	CD4⁺ < 200 cells/mm³ or < 14% unexplained fever for >= 2 weeks oropharyngeal candidiasis	TMP-SMX 1 DS PO qd	TMP-SMX 1 SS PO qd or 1 DS PO tiw dapsone 50 mg PO bid or 100 mg PO qd dapsone 50 mg PO qd, plus pyrimethamine 50 mg PO qw, plus leucovorin 25 mg PO qw, dapsone 200 mg PO qw, plus pyrimethamine 75 mg PO qw, plus leucovorin 25 mg PO qw aerosolized pentamidine 300 mg qm via Respirgard II nebulizer
Mycobacterium tuberculosis Isoniazid- sensitive	TST reaction of >= 5 mm or prior positive TST result with treatment or contact with case of active tuberculosis	isoniazid 300 mg PO, plus pyridoxine 50 mg PO qd x 12 months isoniazid 900 mg PO, plus pyridoxine 50 mg PO biw x 12 months	rifampin 600 mg PO qd x 12 months
Mycobacterium tuberculosis Isoniazid- resistant	same as above, high probability of exposure to isoniazid-resistant tuberculosis	rifampin 600 mg PO qd x 12 months	rifabutin 300 mg PO qd x 12 months
Mycobacterium tuberculosis Multidrug- resistant (isoniazid and rifampin)	same as above, high probability of exposure to multidrug-resistant tuberculosis	choice of drugs requires consultation with public health authorities	none
Toxplasma gondii	IgG antibody to toxoplasma and CD4⁺ < 100 cells/mm³	TMP-SMX 1 DS PO qd	TMP-SMX 1 SS PO qd or 1 DS PO tiw dapsone 50 mg PO qd, plus pyrimethamine 50 mg PO qw, plus leucovorin 25 mg PO qw
Adapted from USPHA/IDSA guidelines for the prevention of opportunistic infections in persons with HIV: A summary. MMWR 1995;44 (RR-8):1-10.

Table 2
PROPHYLAXIS OF FIRST EPISODE OF OPPORTUNISTIC DISEASES IN HIV-INFECTED ADULTS: RECOMMENDED FOR CONSIDERATION IN ALL PATIENTS
		PREVENTIVE REGIMENS
PATHOGEN	INDICATION	FIRST CHOICE	ALTERNATIVES
Streptococcus pneumoniae	all patients	pneumococcal vaccine 0.5 ml IM x 1	none
Mycobacterium avium complex^*	CD4⁺ <75 cells/mm³	clarithromycin 500 mg PO bid azithromycin 1200 mg PO weekly	rifabutin 300 mg PO qd (AI)
Adapted from USPHA/IDSA guidelines for the prevention of opportunistic infections in persons with HIV: A summary. MMWR* 1995;44 (RR-8):1-10.* * Note: Although the USPHS/IDSA guidelines do not include MAC prophylaxis as ?Standard of Care? therapy, most experts now agree that the proven survival advantage demonstrated with clarithromycin makes prophylaxis mandatory.

Table 3
PROPHYLAXIS OF FIRST EPISODE OF OPPORTUNISTIC DISEASES IN HIV-INFECTED ADULTS: INDICATED FOR CONSIDERATION IN SELECTED PATIENTS
		PREVENTIVE REGIMENS
PATHOGEN	INDICATION	FIRST CHOICE	ALTERNATIVES
Bacteria	neutropenia stimulating factor 5-10 µg/kg sc qd x 2-4 w; or granulocyte macrophage- colony stimulating factor 250 µg/m2 over 2 h qd x 2-4 w	granulocyte- colony	none
Candida species	CD4⁺ <50 cells/mm³ PO qd	fluconazole 100-200 mg	ketoconazole 200 mg PO qd
Cryptococcus neoformans	CD4⁺ <50 cells/mm³ PO qd	fluconazole 100-200 mg	itraconazole 200mg PO qd
Histoplasma capsulatum	CD4⁺ <50 cells/mm³, endemic geographic area	itraconaxole 200 mg	fluconazole 200 mg PO qd
Coccidiodes immitis	CD4⁺ <50 cells/mm³, endemic geographic region	fluconazole 100-200 mg	itraconazole 200 mg PO qd
CMV	CD4+ <50 cells/mm³, CMV antibody positivity	ganciclovir 1 g PO tid	valaciclovir 2 g qid (prevents CMV but may hasten death)
Unknown (herpesviruses)?	CD4⁺ <200 cells/mm³	acyclovir 800 mg PO qid	acyclovir 200 mg PO tid
Hepatitis B virus	all susceptible (anti-HBc-negative) patients	Energix-B, 20 µg IMx3 Recombivax HB, 10 µg IMx3	none
Influenza virus	all patients (annually, before influenza season)	whole or split virus, 0.5 mL im/y	rimantadine 200 mg PO bid
Herpes simplex virus	any CD4⁺ cell count history of recurrences <= every 6 weeks	acyclovir 400 - 800 mg PO bid	amantadine 100 mg PO bid
Adapted from USPHA/IDSA guidelines for the prevention of opportunistic infections in persons with HIV: A summary. MMWR* 1995;44 (RR-8):1-10.*

This article was provided by Johns Hopkins AIDS Service. It is a part of the publication Hopkins HIV Report.

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