AUTHOR AND EDITOR INFORMATION

Section 1 of 7  

• Authors and Editors
• General Guidelines for Prophylaxis
• Primary Prophylaxis Strongly Recommended as the Standard of Care
• Generally Recommended Prophylaxis11, 1
• Opportunistic Infections for Which Primary Prophylaxis Is Rarely Indicated
• Secondary Prophylaxis
• References

GENERAL GUIDELINES FOR PROPHYLAXIS

Section 2 of 7  

• Authors and Editors
• General Guidelines for Prophylaxis
• Primary Prophylaxis Strongly Recommended as the Standard of Care
• Generally Recommended Prophylaxis11, 1
• Opportunistic Infections for Which Primary Prophylaxis Is Rarely Indicated
• Secondary Prophylaxis
• References

What determines the risk for opportunistic infections in persons infected with HIV?

All individuals infected with HIV are susceptible to a wide array of opportunistic infections, in addition to infections that are pathogenic to hosts without HIV infection. The latter infections tend to be more common and more severe in persons with HIV infection. In all individuals, the risk of all infections, both opportunistic and nonopportunistic, increases as the absolute CD4 lymphocyte count falls, especially to fewer than 200 cells/μL. Therefore, the CD4 count must be current to within 4 months to determine the risk of infection in a specific patient.

What nonpharmacologic steps can be taken to avoid opportunistic infections?

The infection-prevention method of exposure avoidance yields poor results for most opportunistic infections. However, persons infected with HIV should practice appropriate hygiene and dietary practice, such as avoiding cat litter, animal bites and scratches, persons with skin infections, raw meats and shellfish, unpasteurized dairy products, and fecal-oral contact. Such persons should also limit occupational or recreational exposure to dirt as much as possible in geographical locales with hyperendemic fungal disease (eg, histoplasmosis, coccidioidomycosis, Penicillium marneffei infection).^{1, 2} Specially treated water is not helpful.

How does cost-effectiveness influence the provision of prophylaxis?

Prophylaxis, including immunization, is expensive, and, except for Pneumocystis pneumonia (PCP) and Mycobacterium avium-intracellulare (MAI) infection, most specific infections are unlikely to develop in any given patient. Clinicians should apply cost-utility analysis to the timing and provision of any prophylaxis. The cost per quality-adjusted life-year (QALY) gained using trimethoprim-sulfamethoxazole prophylaxis for PCP has been estimated at $16,000, with weekly azithromycin prophylaxis for MAI at $35,000, both considered acceptable. Conversely, primary prophylaxis for fungal infection, including with Cryptococcus species, carries a QALY cost of $100,000, and cytomegalovirus (CMV) prophylaxis with oral ganciclovir carries a QALY cost of $314,000.³

With improvements in antiretroviral therapy, these QALY costs may now be inaccurate, since prophylaxis can often be terminated when CD4 counts recover and because of the recent availability of bioequivalent generic ganciclovir.⁴

What factors dictate the initiation of prophylaxis and treatment?

In the absence of widespread HIV screening, many HIV infections are diagnosed late and when opportunistic infections have already developed.⁵ Such patients usually have very low CD4 counts and need prompt secondary prophylaxis for the presenting opportunistic infection, as well as additional CD4 count–appropriate primary prophylaxis. In most instances, such preventive therapy is applied prior to the initiation of antiretroviral therapy. Many of these patients have significant psychiatric, social, and economic problems, as well as major medical comorbidities and drug abuse. The patient must address and control these issues if prophylaxis is to be successful, requiring motivation and cooperation on the part of the patient.⁶

Clinicians should withhold antiretroviral therapy until the patient has demonstrated mastery of the prophylactic regimen. (Exceptions include cases in which renal, hematologic, or neurologic disease is directly attributed to HIV viremia.) Otherwise, antiretroviral failure and resistance are extremely likely in such unprepared patients.

At what CD4 count should specific prophylaxes be initiated?

The following CD4 counts are useful landmarks for initiation of prophylaxis:

• CD4 count of fewer than 200 cells/μL - PCP prophylaxis
• CD4 count of fewer than 100 cells/μL - Toxoplasmosis prophylaxis (if seropositive)
• CD4 count of fewer than 50 cells/μL - MAI infection prophylaxis

Is prophylaxis associated with any adverse effects?

Adverse drug reactions to prophylactic therapy are common and should be expected. Patients should completely understand the purpose of the prophylaxis, the possible adverse effects, and what to do if they occur.

Typical toxicities include rash and neutropenia with trimethoprim-sulfamethoxazole, rash and anemia with dapsone, gastrointestinal distress (pain and diarrhea) with azithromycin, leukopenia with pyrimethamine, and hepatitis with itraconazole (less likely with fluconazole).

What are the risks of instituting prophylaxis in a patient with active infection?

Prior to initiation of prophylaxis, the clinician should attempt to clinically exclude active disease, as the prophylactic regimen may not suffice in aborting uncontrolled infection or may even mask signs of infection. In most cases, obtaining a thorough history and conducting an examination with symptom-targeted laboratory and radiological tests are enough to exclude active PCP, MAI infection, and tuberculosis.

What initial tests and prophylaxes should be administered at the first visit?

On the patient's first visit, serologies for syphilis; hepatitis A, B, and C; and toxoplasmosis should be obtained. Although authorities recommend that CMV serology be performed, the author has not encountered a single patient with negative results in 25 years. Urine chlamydia and gonorrheal nucleic acid amplification testing should be performed in all patients with newly diagnosed HIV infection; however, positive results should be confirmed because of relatively low specificity. A purified protein derivative (PPD) skin test should be placed unless a prior positive result for tuberculosis has been documented.

Pneumococcal polysaccharide vaccine should be administered on the first visit, and, on subsequent visits, vaccines for hepatitis A, hepatitis B, diphtheria-tetanus, and influenza should be administered as indicated by serology results, history, and season, respectively. (For general information on vaccines, see Medscape's Vaccines Resource Center.)

How is patient compliance monitored?

Once initiated, prophylaxis should be accompanied by education from a trained educator and such teaching documented. The same educator should reinforce later antiretroviral therapy. At each visit, patients should bring their prescription bottles and explain their purpose. Failure to give correct answers or to bring bottles warrants a return visit to the educator.

At what clinical landmarks can prophylaxis be terminated?

MAI infection prophylaxis, once started, should be continued with antiretroviral therapy until the CD4 count exceeds 100 cells/μL for 3 months.⁷ Similarly, PCP and toxoplasmosis prophylaxis should be continued until the CD4 count exceeds 200 cells/μL for 3 months.^{8, 4}

PRIMARY PROPHYLAXIS STRONGLY RECOMMENDED AS THE STANDARD OF CARE

Section 3 of 7  

• Authors and Editors
• General Guidelines for Prophylaxis
• Primary Prophylaxis Strongly Recommended as the Standard of Care
• Generally Recommended Prophylaxis11, 1
• Opportunistic Infections for Which Primary Prophylaxis Is Rarely Indicated
• Secondary Prophylaxis
• References

What are the useful indications and regimens for prophylaxis of Pneumocystis pneumonia (PCP)?

Indications for prophylaxis include a CD4 cell count of fewer than 200 cells/μL or prior documented PCP infection at a CD4 count above 200 cells/μL. The preferred regimen is trimethoprim-sulfamethoxazole 1 double-strength tablet PO daily or 1 double-strength tablet PO 3 times per week. Alternatives include dapsone 100 mg PO daily (however, see toxoplasmosis) or atovaquone suspension 750 mg (5 mL) PO twice daily.

What are the useful indications and regimens for prophylaxis of M tuberculosis infection?

A course of prophylaxis is indicated for all patients with a history of positive tuberculin skin test result of 5 mm or greater or an FDA-approved serological test who have not previously received such therapy. Patients who have had significant exposure to active tuberculosis should be referred to public health authorities for consideration of prophylaxis and monitoring. Active tuberculosis should be excluded before prophylactic regimens are started. Active tuberculosis may be more likely in a patient with previous active tuberculosis (treated or untreated) than in a patient without a history of tuberculosis.⁹

Regimens depend on the likelihood that the patient is infected with resistant tuberculous bacilli. The preferred regimen for probable infection with latent isoniazid-sensitive bacilli is isoniazid 300 mg plus pyridoxine 50 mg PO daily for 9 months. Patients with suspected isoniazid-resistant infection should receive prophylaxis with rifampin 600 mg daily for 4 months. In patients with multidrug-resistant tuberculosis (MDR) or extensively drug-resistant tuberculosis (XDR), public health authorities should be consulted for recommended regimens and supervision.^{1, 10}

What are the useful indications and regimens for prophylaxis of Toxoplasma gondii infection?

Patients with a CD4 count of fewer than 100 cells/μL who are not previously known to be seronegative for toxoplasma immunoglobulin G (IgG) should receive prophylaxis for toxoplasmosis. Trimethoprim-sulfamethoxazole double-strength tablet PO once daily is preferred. Dapsone alone is ineffective against toxoplasmosis. Therefore, dapsone 50 mg PO daily plus pyrimethamine 50 mg PO weekly plus leucovorin 25 mg PO weekly is appropriate for both PCP and toxoplasmosis.

What are the useful indications and regimens for prophylaxis of M avium-intracellulare (MAI) infection?

Patients with CD4 count of fewer than 50 cells/μL should be given azithromycin 1200 mg PO weekly. Alternatives include clarithromycin 500 mg PO bid or rifabutin 300 mg PO daily.

What are the useful indications and regimens for prophylaxis of varicella-zoster virus infection?

Because the varicella and zoster vaccines are live-virus vaccines, they should not be administered to persons with HIV seropositivity. Persons without a prior history of chickenpox or previous vaccination who have a significant exposure to zoster or chickenpox should receive varicella-zoster immune globulin (VZIG) within 48-96 hours. The typical adult dose is 5 vials IM (1.25 mL per vial).

GENERALLY RECOMMENDED PROPHYLAXIS^{11, 1}

Section 4 of 7  

• Authors and Editors
• General Guidelines for Prophylaxis
• Primary Prophylaxis Strongly Recommended as the Standard of Care
• Generally Recommended Prophylaxis11, 1
• Opportunistic Infections for Which Primary Prophylaxis Is Rarely Indicated
• Secondary Prophylaxis
• References

What are the indications and timing of vaccination against Streptococcus pneumoniae infection?

The USPHS/IDSA guidelines recommend pneumococcal vaccination every 5 years. This should be started very soon after diagnosis. However, the efficacy of the vaccine is questionable in patients with a CD4 count of below 200 cells/μL. These guidelines suggest considering early revaccination when the CD4 count rises above 200 cells/μL, but without evidence.

What are the indications for vaccination against hepatitis B virus infection?

All susceptible (anti-HBc–negative) patients should receive the 3-dose hepatitis B vaccine.

What are the indications for vaccination against influenza virus infection?

All patients should receive inactivated trivalent influenza vaccine annually before the influenza season.

What are the indications for vaccination against hepatitis A virus infection?

All susceptible (anti-HAV–negative) patients should receive the 2-dose hepatitis A vaccine.

OPPORTUNISTIC INFECTIONS FOR WHICH PRIMARY PROPHYLAXIS IS RARELY INDICATED

Section 5 of 7  

• Authors and Editors
• General Guidelines for Prophylaxis
• Primary Prophylaxis Strongly Recommended as the Standard of Care
• Generally Recommended Prophylaxis11, 1
• Opportunistic Infections for Which Primary Prophylaxis Is Rarely Indicated
• Secondary Prophylaxis
• References

What fungal or yeast infections occur in patients infected with HIV for which routine prophylaxis is not necessary?

Oral-pharyngeal, vaginal, and esophageal Candida infection is common and can be troublesome, particularly in patients with diabetes and in patients on trimethoprim-sulfamethoxazole and azithromycin who have a very low CD4 cell count. Such patients may require multiple courses of fluconazole. (The author prefers 200 mg PO daily for 7 d.) After 2 relapses, the author keeps such patients on fluconazole 200 mg daily and rarely encounters resistant Candida infection. Topical oral clotrimazole or nystatin has been advocated in this situation¹ to decrease resistance rates, but this therapy can be difficult for patients.

Cryptococcus neoformans, Histoplasma capsulatum, Coccidioides immitis, and P marneffei represent significant opportunistic infections in some parts of the world. Primary drug prophylaxis has not been shown to increase longevity and would be very expensive. Limitation of exposure may be recommended. Secondary prophylaxis after intensive treatment is usually conducted, at least until the CD4 count has recovered to 200 cells/μL. Fluconazole therapy may be difficult to withdraw from patients with cryptococcosis, since the cryptococcal antigen rarely returns to acceptably low levels.

Fortunately, aspergillosis and phycomycosis (mucormycosis) are rare in individuals infected with HIV. These infections should be considered in patients with invasive sinusitis and focal pulmonary lesions but do not warrant prophylaxis.

What bacterial infections occur in individuals infected with HIV for which routine prophylaxis is not indicated?

Community and health-care–associated infections with methicillin-resistant Staphylococcus aureus, streptococcal cellulitis, Campylobacter species, Salmonella species, Shigella species, Mycoplasma species, Rhodococcus species, Legionella species, Bartonella species, and gram-negative urinary tract and pulmonary infections are not uncommon in patients infected with HIV. Prophylaxis (primary or secondary) is seldom indicated forthese infections.

Persons infected with HIV are at high risk for sexually transmitted diseases such as syphilis, chlamydia, and gonorrhea. These should be reported to authorities and treated with documented cure and provision of counseling to avoid reinfection. Nocardia infection is rare in even late stages of AIDS, probably because it is inhibited serendipitously by Pneumocystis pneumonia (PCP) prophylaxis with trimethoprim-sulfamethoxazole.

What protozoal and helminthic infections occur in patients infected with HIV for which routine prophylaxis is not indicated?

Patients infected with HIV are at risk for infections with Cryptosporidium species, Giardia species, Isospora species, Cyclospora species, and Microsporidia species, as well as Entamoeba species and Strongyloidiasis species in some locales. Neither primary nor secondary prophylaxis is indicated. Concomitant malaria and HIV is a major problem in Africa, but trimethoprim-sulfamethoxazole may have some prophylactic benefit.¹²

What other viral infections occur in patients infected with HIV for which routine prophylaxis is not indicated?

Recurrent genital and, occasionally, oral herpes simplex infections, zoster, molluscum contagiosum, and human papillomavirus infections are common. Primary infections are best avoided. Recurrent herpes simplex and zoster may be prevented with acyclovir 400 mg daily or twice daily. The efficacy of human papillomavirus vaccine is unknown in patients infected with HIV.¹³

SECONDARY PROPHYLAXIS

Section 6 of 7  

• Authors and Editors
• General Guidelines for Prophylaxis
• Primary Prophylaxis Strongly Recommended as the Standard of Care
• Generally Recommended Prophylaxis11, 1
• Opportunistic Infections for Which Primary Prophylaxis Is Rarely Indicated
• Secondary Prophylaxis
• References

What is recommended as secondary prophylaxis for Pneumocystis pneumonia (PCP)?

Trimethoprim-sulfamethoxazole double-strength tablet PO daily until the CD4 count exceeds 200 cells/μL for 3 months

What is recommended as secondary prophylaxis for toxoplasmosis?

Sulfadiazine 500-1000 mg PO 4 times/day plus pyrimethamine 25-50 mg PO daily and leucovorin 10-25 mg PO daily until the CD4 count exceeds 200 cells/μL for 6 months

What is recommended as secondary prophylaxis for M avium-intracellulare infection?

Clarithromycin 500 mg PO bid plus ethambutol 15 mg/kg PO daily with or without rifabutin 300 mg PO daily for 12 months, with the CD4 count greater than 100 cells/μL for 6 months

What is recommended as secondary prophylaxis for cytomegalovirus (CMV) disease?

Maintenance therapy is indicated only for CMV retinitis (usually intraocular sustained-release ganciclovir [Vitrasert ophthalmic implant] plus oral valganciclovir 900 mg PO daily with food) and neurologic disease (oral valganciclovir 900 mg PO daily). Recent government guidelines suggest discontinuation of suppression after antiretroviral therapy has increased the CD4 count to greater than 100 cells/μL for 6 months.¹⁴

What is recommended as secondary prophylaxis for cryptococcal disease?

Fluconazole 200 mg PO daily, at least until the CD4 count exceeds 200 cells/μL for 6 months. The author prefers to stop treatment only after the serum cryptococcal antigen level is very low (<1:4).

What is recommended as secondary prophylaxis for mucocutaneous and esophageal Candida infection?

Long-term suppressive therapy is usually not indicated or necessary, especially if the CD4 count rises to greater than 200 cells/μL. Topical nystatin swish and swallow or clotrimazole troches are preferred prophylaxis,¹ but these may be unsatisfactory for patients with a CD4 count that is persistently fewer than 100 cells/μL. In these situations, the author administers daily fluconazole 200 mg or higher, as needed.

What is recommended as secondary prophylaxis for recurrent herpes simplex infection?

Acyclovir 400 mg PO daily

What is recommended as secondary prophylaxis for recurrent methicillin-resistant S aureus infection?

The recommendation is mupirocin 2% nasal ointment to each nostril twice daily for 5 days if colonization is documented. Long-term efficacy is uncertain, and resistance may develop. Germicidal soaps have been recommended for perineal colonization, but little evidence suggests efficacy. Hygienic measures should be emphasized¹⁵ for this epidemic problem.¹⁶

REFERENCES

Section 7 of 7

• Authors and Editors
• General Guidelines for Prophylaxis
• Primary Prophylaxis Strongly Recommended as the Standard of Care
• Generally Recommended Prophylaxis11, 1
• Opportunistic Infections for Which Primary Prophylaxis Is Rarely Indicated
• Secondary Prophylaxis
• References

1. Masur H. Management of Opportunistic Infections Associated with Human Immunodeficiency Virus Infection. In: Mandell GL, Bennett JE, Dolin R, eds. Mandell, Douglas, and Bennett's Principles and Practice of Infectious Diseases. 6^th ed. Elsevier Churchill Livingstone; 2006:1679-704.
2. Ustianowski AP, Sieu TP, Day JN. Penicillium marneffei infection in HIV. Curr Opin Infect Dis. Feb 2008;21(1):31-6. [Medline].
3. Freedberg KA, Scharfstein JA, Seage GR 3rd, Losina E, Weinstein MC, Craven DE, et al. The cost-effectiveness of preventing AIDS-related opportunistic infections. JAMA. Jan 14 1998;279(2):130-6. [Medline].
4. Furrer H, Opravil M, Bernasconi E, Telenti A, Egger M. Stopping primary prophylaxis in HIV-1-infected patients at high risk of toxoplasma encephalitis. Swiss HIV Cohort Study. Lancet. Jun 24 2000;355(9222):2217-8. [Medline].
5. Battegay M, Fluckiger U, Hirschel B, Furrer H. Late presentation of HIV-infected individuals. Antivir Ther. 2007;12(6):841-51. [Medline].
6. Treisman GJ. Adherence, Psychiatric Disorders and HIV. Medscape. Available at http://www.medscape.com/viewprogram/6727. Accessed 10 March 08.
7. El-Sadr WM, Burman WJ, Grant LB, Matts JP, Hafner R, Crane L, et al. Discontinuation of prophylaxis for Mycobacterium avium complex disease in HIV-infected patients who have a response to antiretroviral therapy. Terry Beirn Community Programs for Clinical Research on AIDS. N Engl J Med. Apr 13 2000;342(15):1085-92. [Medline].
8. Trikalinos TA, Ioannidis JP. Discontinuation of Pneumocystis carinii prophylaxis in patients infected with human immunodeficiency virus: a meta-analysis and decision analysis. Clin Infect Dis. Dec 1 2001;33(11):1901-9. [Medline].
9. Nahid P, Daley CL. Prevention of tuberculosis in HIV-infected patients. Curr Opin Infect Dis. Apr 2006;19(2):189-93. [Medline].
10. Andrews JR, Shah NS, Gandhi N, Moll T, Friedland G. Multidrug-resistant and extensively drug-resistant tuberculosis: implications for the HIV epidemic and antiretroviral therapy rollout in South Africa. J Infect Dis. Dec 1 2007;196 Suppl 3:S482-90. [Medline].
11. Kaplan JE, Masur H, Holmes KK. Guidelines for preventing opportunistic infections among HIV-infected persons--2002. Recommendations of the U.S. Public Health Service and the Infectious Diseases Society of America. MMWR Recomm Rep. Jun 14 2002;51:1-52. [Medline]. [Full Text].
12. Herrero MD, Rivas P, Rallón NI, Ramírez-Olivencia G, Puente S. HIV and malaria. AIDS Rev. Apr-Jun 2007;9(2):88-98. [Medline].
13. De Vuyst H, Franceschi S. Human papillomavirus vaccines in HIV-positive men and women. Curr Opin Oncol. Sep 2007;19(5):470-5. [Medline].
14. Benson CA, Kaplan JE, Masur H, Pau A, Holmes KK. Treating opportunistic infections among HIV-infected adults and adolescents: recommendations from CDC, the National Institutes of Health, and the HIV Medicine Association/Infectious Diseases Society of America. MMWR Recomm Rep. Dec 17 2004;53:1-112. [Medline].
15. Daum RS. Clinical practice. Skin and soft-tissue infections caused by methicillin-resistant Staphylococcus aureus. N Engl J Med. Jul 26 2007;357(4):380-90. [Medline].
16. Diep BA, Chambers HF, Graber CJ, Szumowski JD, Miller LG, Han LL, et al. Emergence of multidrug-resistant, community-associated, methicillin-resistant Staphylococcus aureus clone USA300 in men who have sex with men. Ann Intern Med. Feb 19 2008;148(4):249-57. [Medline].
17. Bozzette SA. Fluconazole prophylaxis in HIV disease, revisited. Clin Infect Dis. Nov 15 2005;41(10):1481-2. [Medline].
18. Freedberg KA, Paltiel AD. Cost effectiveness of prophylaxis for opportunistic infections in AIDS. An overview and methodological discussion. Pharmacoeconomics. Aug 1998;14(2):165-74. [Medline].

Article Last Updated: Aug 13, 2008
Topic originally published: Aug 13, 2008