Opportunistic infections

U.S. DEPARTMENT OF HEALTH AND HUMAN SERVICES, PUBLIC HEALTH SERVICE CENTERS FOR DISEASE CONTROL AND PREVENTION, Atlanta, Georgia

This third part of the "Guidelines for the Prevention of Opportunistic Infections in Persons with Human Immunodeficiency Virus" gives recommendations for the prevention of recurrence of opportunistic disease, after chemotherapy for acute disease. Recommendations are rated by a revised version of the Infectious Diseases Society of America (IDSA) rating system (Table 1 [page 772]).1 In this system, the letters A through E signify the strength of the recommendation for or against a preventive modality, and Roman numerals I through III indicate the quality of evidence supporting the recommendation.

Dosages for prophylaxis to prevent recurrence of opportunistic disease in HIV-infected adults and adolescents are given in Table 2 (page 774), dosages to prevent recurrence in infants and children are given in Table 3 (page 776) and criteria for discontinuing and restarting prophylaxis for opportunistic infections in adults with HIV infection are given in Table 4 (page 778).

This report is oriented toward the prevention of specific opportunistic infections in persons with human immunodeficiency virus (HIV) infection in the United States and other industrialized countries. Recommendations for use of antiretroviral therapy that is designed to prevent immunologic deterioration and delay the need for many of the chemoprophylactic strategies described in this report are published elsewhere,2 as are integrated approaches to the care of HIV-infected persons.3

New data on prevention of opportunistic infections in HIV-infected persons are emerging, and randomized controlled trials addressing some unresolved issues in opportunistic infection prophylaxis are ongoing. The Opportunistic Infection Working Group has therefore developed a mechanism for routinely and periodically reviewing emerging data and updating these guidelines on a regular basis. The most recent information will be available from the AIDS Treatment Information Service (ATIS) Web site (http://www.hivatis.org).

Disease-Specific Recommendations for the Prevention of Disease Recurrence pneumocystis carinii pneumonia

Adults and adolescents who have a history of Pneumocystis carinii pneumonia should be administered chemoprophylaxis (i.e., secondary prophylaxis or chronic maintenance therapy) with the regimens described in part II to prevent recurrence (AI).4

Discontinuation of Secondary Prophylaxis (Chronic Maintenance Therapy). Although patients receiving secondary prophylaxis (prior episode of P. carinii pneumonia) might also be at low risk for P. carinii pneumonia when their CD4+ T-lymphocyte counts increase to greater than 200 per mm3 (200 3 106 per L), inadequate numbers of patients have been evaluated to warrant a recommendation to discontinue prophylaxis in such patients.

Children. Children who have a history of P. carinii pneumonia should be administered lifelong chemoprophylaxis to prevent recurrence (AI).5

toxoplasmic encephalitis

Patients who have had toxoplasmic encephalitis should be administered lifelong suppressive therapy (secondary prophylaxis or chronic maintenance therapy) with drugs active against Toxoplasma to prevent relapse (AI).6,7 The combination of pyrimethamine plus sulfadiazine and

leucovorin is highly effective for this purpose (AI).6,7 A commonly used regimen in patients who cannot tolerate sulfa drugs is pyrimethamine plus clindamycin (BI); however, only the combination of pyrimethamine plus sulfadiazine appears to provide protection against P. carinii pneumonia as well (AII).

Discontinuation of Secondary Prophylaxis (Chronic Maintenance Therapy). The number of patients who have stopped maintenance therapy after responding to highly active antiretroviral therapies (HAART) is insufficient to warrant recommending discontinuation of maintenance therapy.

Pregnant Women. For prophylaxis against recurrent toxoplasmic encephalitis, the health care provider and clinician should be well informed about the benefit of lifelong therapy for the mother, given the high likelihood that disease will recur promptly if therapy is stopped (AIII).

cryptosporidiosis

No drug regimens are known to be effective in preventing the recurrence of cryptosporidiosis.

microsporidiosis

No chemotherapeutic regimens are known to be effective in preventing the recurrence of microsporidiosis.

tuberculosis

Chronic suppressive therapy for a patient who has successfully completed a recommended regimen of treatment for tuberculosis is not necessary (DII).

disseminated infection with mycobacterium avium complex

Patients who have been treated for disseminated Mycobacterium avium complex (MAC) disease should continue to receive full therapeutic dosages of antimycobacterial agents for life (i.e., secondary prophylaxis or chronic maintenance therapy) (AII).8 Unless good clinical or laboratory evidence of macrolide resistance exists, the use of a macrolide antibiotic (clarithromycin or, alternatively, azithromycin) is recommended in combination with ethambutol (AII) with or without rifabutin (CI).9,10 Treatment of MAC disease with clarithromycin in a dosage of 1,000 mg twice a day is associated with a higher mortality rate than has been observed with clarithromycin administered at 500 mg twice a day; thus, the higher dosage should not be used (EI).11,12 Clofazimine has been associated with an adverse clinical outcome in the treatment of MAC disease and should not be used (DII).12,13

Discontinuation of Secondary Prophylaxis (Chronic Maintenance Therapy). Although patients receiving chronic maintenance therapy for MAC might be at low risk for recurrence of MAC when their CD4+ T-lymphocyte counts increase to greater than 100 per mm3 (100 3 106 per L) following six to 12 months of HAART, the number of patients who have been evaluated is insufficient to warrant a recommendation to discontinue maintenance therapy in such patients.

Drug Interactions. Rifabutin should not be administered with certain protease inhibitors or nonnucleoside reverse transcriptase inhibitors (see the Drug Interactions section in the Tuberculosis section, part II). Although protease inhibitors might also increase clarithromycin levels, no recommendation to adjust the dosage of clarithromycin or protease inhibitors can be made on the basis of existing data.

Pregnant Women. For secondary prophylaxis (chronic maintenance therapy), azithromycin plus ethambutol are the preferred drugs (BIII).

bacterial respiratory infections

Some clinicians administer antibiotic chemoprophylaxis to HIV-infected patients who have frequent recurrences of serious bacterial respiratory infections (CIII). Trimethoprim-sulfamethoxazole (TMP-SMZ), administered for P. carinii pneumonia prophylaxis, and clarithromycin or azithromycin, administered for MAC prophylaxis, are appropriate for drug-sensitive organisms. However, providers should be cautious about using antibiotics solely for preventing the recurrence of serious bacterial respiratory infections because of the potential development of drug-resistant microorganisms and drug toxicity.

Children. To prevent recurrence of serious bacterial respiratory infections, antibiotic chemoprophylaxis may be considered (BI). However, providers should be cautious about using antibiotics solely for this purpose because of the potential development of drug-resistant microorganisms and drug toxicity. The administration of intravenous immunoglobulin (IVIG) should also be considered in HIV-infected children who have recurrent serious bacterial infections (BI), although such treatment might not provide additional benefit to children who are being administered daily TMP-SMZ. However, IVIG may be considered in children who have recurrent serious bacterial infections despite receiving TMP-SMZ or other antimicrobials (CIII).

bacterial enteric infections

HIV-infected persons who have Salmonella septicemia require long-term therapy (i.e., secondary prophylaxis or chronic maintenance therapy) to prevent recurrence. Fluoroquinolones, primarily ciprofloxacin, are usually the drugs of choice for susceptible organisms (BII).

Household contacts of HIV-infected persons who have salmonellosis or shigellosis should be evaluated for persistent asymptomatic carriage of Salmonella or Shigella so that strict hygienic measures or antimicrobial therapy, or both, can be instituted, and recurrent transmission to the HIV-infected person can be prevented (CIII).

Children. HIV-infected children who have Salmonella septicemia should be offered long-term therapy to prevent recurrence (CIII). TMP-SMZ is the drug of choice; ampicillin or chloramphenicol can be used if the organism is susceptible. Fluoroquinolones should be used with caution and only if no alternative exists.

infection with bartonella (formerly rochalimaea)

Relapse or reinfection with Bartonella has sometimes followed a course of primary treatment. Although no firm recommendation can be made regarding prophylaxis in this situation, long-term suppression of infection with erythromycin or doxycycline should be considered (CIII).

Pregnant Women. If long-term suppression of Bartonella infection is required, erythromycin should be used. Tetracyclines should not be used during pregnancy.

candidiasis

Many experts do not recommend chronic prophylaxis of recurrent oropharyngeal or vulvovaginal candidiasis for the same reasons that they do not recommend primary prophylaxis. However, if recurrences are frequent or severe, providers may consider administering an oral azole (fluconazole [CI]14 or itraconazole solution [CI]). Other factors that influence choices about such therapy include the impact of the recurrences on the patient's well-being and quality of life, the need for prophylaxis for other fungal infections, cost, toxicities, drug interactions and the potential to induce drug resistance among Candida and other fungi. Prolonged use of systemically absorbed azoles, particularly in patients with low CD4+ T-lymphocyte counts (i.e., less than 100 per mm3), increases the risk for the development of azole resistance.

Adults or adolescents who have a history of documented esophageal candidiasis, particularly multiple episodes, should be considered candidates for chronic suppressive therapy. Fluconazole at a dosage of 100 to 200 mg daily is appropriate (BI). However, the potential development of azole resistance should be taken into account when long- term azole therapy is considered.

Children. Suppressive therapy with systemic azoles should be considered in infants who have severe recurrent mucocutaneous candidiasis (CIII) and particularly in those who have esophageal candidiasis (BIII).

cryptococcosis

Patients who complete initial therapy for cryptococcosis should be administered lifelong suppressive treatment (i.e., secondary prophylaxis or chronic maintenance therapy). Fluconazole is superior to itraconazole in preventing relapse of cryptococcal disease and is the preferred drug (AI).

Discontinuation of Secondary Prophylaxis (Chronic Maintenance Therapy). Although patients receiving secondary prophylaxis (chronic maintenance therapy) might be at low risk for recurrence of systemic mycosis when their CD4+ T-lymphocyte counts increase to greater than 100 per mm3 on HAART, the number of patients who have been evaluated is insufficient to warrant a recommendation to discontinue prophylaxis.

Children. No data exist on which to base specific recommendations for children, but lifelong suppressive therapy with fluconazole after an episode of cryptococcosis is appropriate (AII).

Pregnant Women. The occurrence of craniofacial and skeletal abnormalities in infants following prolonged in utero exposure to fluconazole should be considered when assessing the therapeutic options for HIV-infected women who become pregnant and are receiving secondary prophylaxis (chronic maintenance therapy) for cryptococcosis.15,16 In such patients, therapy with amphotericin B may be preferred, especially during the first trimester. Effective birth-control measures should be recommended to all HIV-infected women on azole therapy for cryptococcosis (AIII).

histoplasmosis

Patients who complete initial therapy for histoplasmosis should be administered lifelong suppressive treatment (i.e., secondary prophylaxis or chronic maintenance therapy) with itraconazole (200 mg twice a day) (AI).17

Discontinuation of Secondary Prophylaxis (Chronic Maintenance Therapy). Although patients receiving secondary prophylaxis (chronic maintenance therapy) might be at low risk for recurrence of systemic mycosis when their CD4+ T-lymphocyte counts increase to greater than 100 per mm3 on HAART, the number of patients who have been evaluated is insufficient to warrant a recommendation to discontinue prophylaxis.

Children. Because primary histoplasmosis can lead to disseminated infection in children, a reasonable option is to administer lifelong suppressive therapy after an acute episode of the disease (AIII).

Pregnant Women. Itraconazole is embryotoxic and teratogenic in animal systems. This information, as well as the observation of craniofacial and skeletal abnormalities in infants following prolonged in utero exposure to fluconazole, should be considered when assessing the need for chronic maintenance therapy in HIV-infected pregnant women with histoplasmosis. In such patients, therapy with amphotericin B may be preferred, especially during the first trimester. Effective birth control measures should be recommended to all HIV-infected women receiving azole therapy for histoplasmosis (AIII).

coccidioidomycosis

Patients who complete initial therapy for coccidioidomycosis should be administered lifelong suppressive therapy (i.e., secondary prophylaxis or chronic maintenance therapy) (AII) using 400 mg of oral fluconazole each day or 200 mg of itraconazole twice a day.18 Patients with meningeal disease require consultation with an expert.

Discontinuation of Secondary Prophylaxis (Chronic Maintenance Therapy). Although patients receiving secondary prophylaxis (chronic maintenance therapy) might be at low risk for recurrence of systemic mycosis when their CD4+ T-lymphocyte counts increase to greater than 100 per mm3 on HAART, the number of patients who have been evaluated is insufficient to warrant a recommendation to discontinue prophylaxis.

Children. Although no specific data are available regarding coccidioidomycosis in HIV-infected children, a reasonable option is to administer lifelong suppressive therapy after an acute episode of the disease (AIII).

Pregnant Women. The potential teratogenicity of fluconazole and itraconazole should be considered when assessing therapeutic options for HIV-infected women who become pregnant while receiving chronic maintenance therapy for coccidioidomycosis. In such patients, therapy with amphotericin B may be preferred, especially during the first trimester. Effective birth control measures should be recommended for all HIV-infected women receiving azole therapy for coccidioidomycosis (AIII).

cytomegalovirus disease

Cytomegalovirus (CMV) disease is not cured with courses of the currently available antiviral agents (e.g., ganciclovir, foscarnet and cidofovir). Following induction therapy, secondary prophylaxis (chronic maintenance therapy) is recommended for life (AI). Regimens that are effective for chronic suppression include parenteral or oral ganciclovir, parenteral foscarnet, combined parenteral ganciclovir and foscarnet, parenteral cidofovir and (for retinitis only) ganciclovir administered via intraocular implant plus oral ganciclovir (AI).19-23 The intraocular implant alone does not provide protection to the contralateral eye or to other organ systems. The choice of a chronic maintenance regimen for patients treated for CMV disease should be made in consultation with an expert. For patients with retinitis, this decision should be made in consultation with an ophthalmologist and should take into consideration the anatomic location of the retinal lesion, vision in the contralateral eye, the immunologic and virologic status of the patient, and the patient's response to HAART (BIII).

Discontinuation of Secondary Prophylaxis (Chronic Maintenance Therapy). Several studies have shown that maintenance therapy can be discontinued in patients with CMV retinitis whose CD4+ T-lymphocyte counts have increased to greater than 100 to 150 per mm3 (100 to 150 3 106 per L) and whose HIV plasma RNA levels have been suppressed in response to HAART.24-26 These patients largely have remained disease-free for more than 30 to 90 weeks, whereas in the pre-HAART era, retinitis typically recurred in six to eight weeks. Discontinuation of prophylaxis may be considered in patients with a sustained (e.g., greater than three- to six-month) increase in CD4+ T-lymphocyte count to greater than 100 to 150 per mm3 on HAART (CIII). Such decisions should be made in consultation with an ophthalmologist and should take into account such factors as magnitude and duration of CD4+ T-lymphocyte increase, magnitude and duration of viral load suppression, anatomic location of the retinal lesion, vision in the contralateral eye and the feasibility of regular ophthalmic monitoring (CII).24-26

Restarting Secondary Prophylaxis. No data exist to guide recommendations for reinstituting secondary prophylaxis. Pending the availability of such data, a reasonable approach would be to restart prophylaxis when the CD4+ T-lymphocyte count has decreased to less than 50 to 100 per mm3 (50 to 100 3 106 per L) (CIII).

Children. For children with CMV disease, no data are available to guide decisions concerning discontinuation of secondary prophylaxis (chronic maintenance therapy) when the CD4+ T-lymphocyte count has increased in response to HAART.

Pregnant Women. Because of the risks to maternal health, prophylaxis against recurrent CMV disease is indicated during pregnancy (AIII). The choice of agents to be used in pregnancy should be individualized after consultation with experts.

herpes simplex virus disease

Because acute episodes of herpes simplex virus (HSV) infection can be treated successfully, chronic therapy with acyclovir is not required after lesions resolve. However, persons who have frequent or severe recurrences can be administered daily suppressive therapy with oral acyclovir or famciclovir (AI).27,28 Valacyclovir is also an option (CIII). Intravenous foscarnet or cidofovir can be used to treat infection that is due to acyclovir-resistant isolates of HSV, which are routinely resistant to ganciclovir as well (AII).

Pregnant Women. In patients who have frequent, severe recurrences of genital HSV disease, acyclovir prophylaxis might be indicated (BIII). No pattern of adverse pregnancy outcomes has been reported after acyclovir exposure.29

varicella-zoster virus infection

No drug has been proved to prevent the recurrence of shingles in HIV- infected persons.

human herpesvirus 8 infection

Effective suppression of HIV replication with antiretroviral drugs in HIV-infected patients with Kaposi's sarcoma might prevent Kaposi's sarcoma progression or the development of new lesions, and should be considered for all persons with Kaposi's sarcoma (BII).

human papillomavirus infection

The risks for recurrence of squamous intraepithelial lesions and cervical cancer after conventional therapy are increased among HIV- infected women. The prevention of illness associated with recurrence depends on careful follow-up of patients after treatment. Patients should be monitored with frequent cytologic screening and, when indicated, with colposcopic examination for recurrent lesions (AI).30

In one recent study of HIV-infected women treated for high-grade squamous intraepithelial lesions using standard therapy, low-dose intravaginal 5-fluorouracil (2 g twice a week for six months) reduced the short-term risk for recurrence and possibly the grade of recurrence.31 However, clinical experience with this therapy is too limited to provide a recommendation for routine use.

Pregnant Women. Use of intravaginal 5-fluorouracil to prevent recurrent dysplasia is not recommended during pregnancy.

hepatitis c virus infection

If the serum hepatitis C virus (HCV) RNA level becomes undetectable during HCV therapy and remains undetectable for six months after HCV therapy is stopped (sustained virologic response), more than 90 percent of HIV-uninfected patients with hepatitis C will remain negative for HCV RNA for more than five years and have improved liver histology.32 In HIV-HCV coinfected patients, the durability of treatment response and requirement for maintenance therapy are unknown.

The 89 references cited in the original document have been divided along with the text into three parts; references are renumbered and listed in order of their citation in each of the three parts.

References

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3. el-Sadr W, Oleske JM, Agins BD. Evaluation and management of early HIV infection. Clinical practice guideline no. 7. Rockville, Md.: U.S. Department of Health and Human Services, Public Health Service, 1994; AHCPR publication no. 94-0572.

4. Centers for Disease Control and Prevention. Guidelines for prophylaxis against Pneumocystis carinii pneumonia for persons infected with human immunodeficiency virus. MMWR 1989; 38(suppl 5):1-9.

5. Centers for Disease Control and Prevention. 1995 revised guidelines for prophylaxis against Pneumocystis carinii pneumonia for children infected with or perinatally exposed to human immunodeficiency virus. MMWR 1995;44(RR-4).

6. Dannemann B, McCutchan JA, Israelski D, Antoniskis D, Leport C, Luft B, et al. Treatment of toxoplasmic encephalitis in patients with AIDS: a randomized trial comparing pyrimethamine plus clindamycin to pyrimethamine plus sulfadiazine. Ann Intern Med 1992;116:33-43.

7. Katlama C, DeWit S, O'Doherty E, Van Glabeke M, Clumeck N. Pyrimethamine-clindamycin vs. pyrimethamine-sulfadiazine as acute and long-term therapy for toxoplasmic encephalitis in patients with AIDS. Clin Infect Dis 1996;22:268-75.

8. Masur H. Recommendations on prophylaxis and therapy for disseminated Mycobacterium avium complex disease in patients infected with the human immunodeficiency virus. Public Health Service Task Force on Prophylaxis and Therapy for Mycobacterium avium Complex. N Engl J Med 1993;329:898- 904.

9. Gordin F, Sullam P, Shafran S, et al. A placebo-controlled trial of rifabutin added to a regimen of clarithromycin and ethambutol in the treatment of M. avium complex (MAC) bacteremia [Abstract]. 12th World AIDS Conference. Geneva: The Conference, 1998. Abstract no. 22176.

10. Benson C, Willaims P, Currier J, et al. ACTG223: an open, prospective, randomized study comparing efficacy and safety of clarithromycin (C) plus ethambutol (E), rifabutin (R), or both for treatment (Rx) of MAC disease in patients with AIDS [Abstract]. In: Program and abstracts: 6th Conference on Retroviruses and Opportunistic Infections. Alexandria, Va.: Foundation for Retrovirology and Human Health, 1999. Abstract no. 249.

11. Chaisson RE, Benson CA, Dube MP, Heifets LB, Korvick JA, Elkin S, et al. Clarithromycin therapy for bacteremic Mycobacterium avium complex disease. A randomized, double-blind, dose-ranging study in patients with AIDS. Ann Intern Med 1994;121:905-11.

12. Cohn DL, Fisher EJ, Peng GT, Hodges JS, Chesnut J, Child CC, et al. A prospective randomized trial of four three-drug regimens in the treatment of disseminated Mycobacterium avium complex disease in AIDS patients: excess mortality associated with high-dose clarithromycin. Clin Infect Dis 1999;29:125-33.

13. Chaisson RE, Keiser P, Pierce M, Fessel WJ, Ruskin J, Lahart C, et al. Clarithromycin and ethambutol with or without clofazimine for the treatment of bacteremic Mycobacterium avium complex disease in patients with HIV infection. AIDS 1997;11:311-7.

14. Powderly WG, Finkelstein DM, Feinberg J, Frame P, He W, van der Horst C, et al. A randomized trial comparing fluconazole with clotrimazole troches for the prevention of fungal infections in patients with advanced human immunodeficiency virus infection. N Engl J Med 1995;332:700-5.

15. Aleck KA, Bartley DL. Multiple malformation syndrome following fluconazole use in pregnancy: report of an additional patient. Am J Med Genet 1997;72:253-6.

16. Pursley TJ, Blomquist IK, Abraham J, Andersen HF, Bartley JA. Fluconazole-induced congenital anomalies in three infants. Clin Infect Dis 1996;22:336-40.

17. Wheat J, Hafner R, Wulfsohn M, Spencer P, Squires K, Powderly W, et al. Prevention of relapse of histoplasmosis with itraconazole in patients with the acquired immunodeficiency syndrome. Ann Intern Med 1993;118:610-6.

18. Galgiani JN, Cloud GA, Catanzaro A, et al. Fluconazole (FLU) vs. itraconazole (ITRA) for coccidioidomycosis: randomized, multicenter, double-blinded trial in nonmeningeal progressive infections [Abstract]. In: Abstracts from 36th Annual Meeting of the Infectious Diseases Society of America. Alexandria, Va.: The Society, 1998. Abstract no. 100.

19. Martin DF, Kupperman BD, Wolitz RA, Palistine AG, Li H, Robinson CA. Oral ganciclovir for patients with cytomegalovirus retinitis treated with a ganciclovir implant. N Engl J Med 1999;340:1063-70.

20. Drew WL, Ives D, Lalezari JP, Crumpacker C, Follansbee SE, Spector SA, et al. Oral ganciclovir as maintenance treatment for cytomegalovirus retinitis in patients with AIDS. N Engl J Med 1995; 333:615-20.

21. Parenteral cidofovir for cytomegalovirus retinitis in patients with AIDS: the HPMPC peripheral cytomegalovirus retinitis trial. A randomized, controlled trial. Ann Intern Med 1997;126:264-74.

22. Palestine AG, Polis MA, De Smet MD, Baird BF, Falloon J, Kovacs JA, et al. A randomized, controlled trial of foscarnet in the treatment of cytomegalovirus retinitis in patients with AIDS. Ann Intern Med 1991;115:665-73.

23. Cytomegalovirus (CMV) culture results, drug resistance, and clinical outcome in patients with AIDS and CMV retinitis treated with foscarnet or ganciclovir. J Infect Dis 1997;176:50-8.

24. MacDonald JC, Torriani FJ, Morse LS, Karavellas MP, Reed JB, Freeman WR. Lack of reactivation of cytomegalovirus (CMV) retinitis after stopping CMV maintenance therapy in AIDS patients with sustained elevations in CD4 T cells in response to highly active antiretroviral therapy. J Infect Dis 1998;177:1182-7.

25. Tural C, Romeu J, Sirera G, Andreu D, Conejero M, Ruiz S, et al. Long-lasting remission of cytomegalovirus retinitis without maintenance therapy in human immunodeficiency virus-infected patients. J Infect Dis 1998;177:1080-3.

26. Vrabec TR, Baldassano VF, Whitcup SM. Discontinuation of maintenance therapy in patients with quiescent cytomegalovirus retinitis and elevated CD4+ counts. Ophthalmology 1998;105:1259-64.

27. Schacker T, Zeh J, Hu HL, Hill E, Corey L. Frequency of symptomatic and asymptomatic herpes simplex virus type 2 reactivations among human immunodeficiency virus-infected men. J Infect Dis 1998;178:1616-22.

28. Schacker T, Hu HL, Koelle DM, Zeh J, Saltzman R, Boon R, et al. Famciclovir for the suppression of symptomatic and asymptomatic herpes simplex virus reactivation in HIV-infected persons. A double-blind, placebo-controlled trial. Ann Intern Med 1998;128:21-8.

29. Centers for Disease Control and Prevention. Pregnancy outcomes following systemic prenatal acyclovir exposure, June 1, 1984-June 30, 1993. MMWR 1993;42:806-9.

30. Kurman RJ, Henson DE, Herbst AL, Noller KL, Schiffman MH. Interim guidelines for management of abnormal cervical cytology. The 1992 National Cancer Institute Workshop. JAMA 1994; 271:1866-9.

31. Maiman M, Watts DH, Andersen J, Clax P, Merino M, Kendall MA. Vaginal 5-fluorouracil for high-grade cervical dysplasia in human immunodeficiency virus infection: a randomized trial. Obstet Gynecol 1999;94:954-61.

32. Chemello L, Cavalletto L, Casarin C, Bonetti P, Bernardinello E, Pontisso P, et al. Persistent hepatitis C viremia predicts late relapse after sustained response to interferon-alpha in chronic hepatitis C. TriVeneto Viral Hepatitis Group. Ann Intern Med 1996;124:1058-60.

This is part III of a three-part series of articles derived from the USPHS/IDSA guidelines. Part I, "Prevention of Exposure," appeared in the January 1 issue (Am Fam Physician 2000;61:163-74), and part II, "Prevention of the First Episode of Disease," appeared in the January 15 issue (Am Fam Physician 2000;61:441-2,445-9,453-4,456-8,460-1,465- 70,472,477).

The original publication, including a list of the U.S. Public Health Service/Infectious Diseases Society of America Prevention of Opportunistic Infections Working Group members who developed this report, can be found in the Centers for Disease Control and Prevention's Morbidity and Mortality Weekly Report 1999;48(RR-10). Single copies of this report can be obtained from the AIDS Treatment Information Service (ATIS) by calling 800-448-0440, 301-217-0023 (international) or 800-243-7012 (TTY); the report can also be downloaded from the ATIS Web site (http://www. hivatis.org). In addition, pamphlets for patients are available from ATIS and can be accessed on the CDC's Division of HIV/AIDS Prevention home page (http://www.cdc.gov/hiv).

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