Am Fam Physician. 2000;61(3):771-785
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).
This is part III of a three-part series of articles derived from the USPHS/IDSA guidelines. New data about the prevention of opportunistic diseases have emerged since the guidelines were first published in 1997, and this section discusses prevention of disease recurrence.
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.
| Rating | Definition |
|---|---|
| Ratings reflecting the strength of each recommendation | |
| A | Strong evidence for efficacy and substantial clinical benefit support recommendation for use. Should always be offered. |
| B | Moderate evidence for efficacy—or strong evidence for efficacy but only limited clinical benefit—supports recommendation for use. Should generally be offered. |
| C | Evidence for efficacy is insufficient to support a recommendation for or against use, or evidence for efficacy might not outweigh adverse consequences (e.g., drug toxicity, drug interactions) or cost of the chemoprophylaxis or alternative approaches. Optional. |
| D | Moderate evidence for lack of efficacy or for adverse outcome supports a recommendation against use. Should generally not be offered. |
| E | Good evidence for lack of efficacy or for adverse outcome supports a recommendation against use. Should never be offered. |
| Ratings reflecting the quality of evidence supporting each recommendation | |
| I | Evidence from at least one properly randomized, controlled trial. |
| II | Evidence from at least one well-designed clinical trial without randomization, from cohort or case-controlled analytic studies (preferably from more than one center) or from multiple time-series studies or dramatic results from uncontrolled experiments. |
| III | Evidence from opinions of respected authorities based on clinical experience, descriptive studies or reports of expert committees. |
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).
| Pathogen | Preventive regimens | ||
|---|---|---|---|
| Indication | First choice | Alternatives | |
| I. Recommended for life as standard of care | |||
| Pneumocystis carinii | Prior P. carinii pneumonia | TMP-SMZ, 1 DS orally daily (AI) TMP-SMZ, 1 SS orally daily (AI) | Dapsone, 50 mg orally twice daily or 100 mg orally daily (BI); dapsone, 50 mg orally daily plus pyrimethamine, 50 mg orally every week plus leucovorin, 25 mg orally every week (BI); dapsone, 200 mg orally plus pyrimethamine, 75 mg orally plus leucovorin, 25 mg orally every week (BI); aerosolized pentamidine, 300 mg every month via Respirgard II nebulizer (BI); atovaquone, 1,500 mg orally daily (BI); TMP-SMZ, 1 DS orally three times weekly (CI) |
| Toxoplasma gondii* | Prior toxoplasmic encephalitis | Sulfadiazine, 500 to 1,000 mg orally four times daily plus pyrimethamine, 25 to 75 mg orally daily plus leucovorin, 10 to 25 mg orally daily (AI) | Clindamycin, 300 to 450 mg orally every 6 to 8 hours plus pyrimethamine, 25 to 75 mg orally daily plus leucovorin, 10 to 25 mg orally daily (BI); atovaquone, 750 mg orally every 6 to 12 hours with or without pyrimethamine, 25 mg orally daily plus leucovorin, 10 mg orally daily (CIII) |
| Mycobacterium avium complex† | Documented disseminated disease | Clarithromycin, 500 mg orally twice daily (AI) plus ethambutol, 15 mg per kg orally daily (AII); with or without rifabutin, 300 mg orally daily (CI) | Azithromycin, 500 mg orally daily (AII) plus ethambutol, 15 mg per kg orally daily (AII); with or without rifabutin, 300 mg orally daily (CI) |
| Cytomegalovirus | Prior end-organ disease | Ganciclovir, 5 to 6 mg per kg IV 5 to 7 days per week or 1,000 mg orally three times daily (AI); or foscarnet, 90 to 120 mg per kg IV daily (AI); or (for retinitis) ganciclovir sustained-release implant every 6 to 9 months plus ganciclovir, 1.0 to 1.5 g orally three times daily (AI) | Cidofovir, 5 mg per kg IV every other week with probenecid, 2 g orally 3 hours before the dose followed by 1 g orally 2 hours after the dose and 1 g orally 8 hours after the dose (total of 4 g) (AI). Fomivirsen, 1 vial (330 μg) injected into the vitreous and repeated every 2 to 4 weeks (AI) |
| Crypotococcus neoformans | Documented disease | Fluconazole, 200 mg orally daily (AI) | Amphotericin B, 0.6 to 1.0 mg per kg IV weekly to three times weekly (AI); itraconazole, 200 mg orally daily (BI) |
| Histoplasma capsulatum | Documented disease | Itraconazole capsule, 200 mg orally twice daily (AI) | Amphotericin B, 1.0 mg per kg IV weekly (AI) |
| Coccidioides immitis | Documented disease | Fluconazole, 400 mg orally daily (AII) | Amphotericin B, 1.0 mg per kg IV weekly (AI); itraconazole, 200 mg orally twice daily (AII) |
| Salmonella species (non-typhi)§ | Bacteremia | Ciprofloxacin, 500 mg orally twice daily for several months (BII) | Antibiotic chemoprophylaxis with another active agent (CIII) |
| II. Recommended only if subsequent episodes are frequent or severe | |||
| Herpes simplex virus | Frequent/severe recurrences | Acyclovir, 200 mg orally three times daily or 400 mg orally twice daily (AI) Famciclovir, 500 mg orally twice daily (AI) | Valacyclovir, 500 mg orally twice daily (CIII) |
| Candida (oropharyngeal or vaginal) | Frequent/severe recurrences | Fluconazole, 100 to 200 mg orally daily (CI) | Itraconazole solution, 200 mg orally daily (CI); ketoconazole, 200 mg orally daily (CIII) |
| Candida (esophageal) | Frequent/severe recurrences | Fluconazole, 100 to 200 mg orally daily (BI) | Itraconazole solution, 200 mg orally daily (BI); ketoconazole, 200 mg orally daily (CIII) |
| Pathogen | Preventive regimens | ||||
|---|---|---|---|---|---|
| Indication | First choice | Alternative | |||
| I. Recommended for life as a standard of care | |||||
| Pneumocystis carinii | Prior P. carinii pneumonia | TMP-SMZ, 150/750 mg per m2 daily in 2 divided doses orally three times weekly on consecutive days (AII) Acceptable alternative schedules for same dosage: (AII) | Dapsone Children ≥1 month: 2 mg per kg (maximum: 100 mg) orally daily or 4 mg per kg (maximum: 200 mg) orally weekly (CII) Aerosolized pentamidine | ||
| Single dose orally three times weekly on consecutive days; 2 divided doses orally daily; 2 divided doses orally three times weekly on alternate days | Aerosolized pentamidine Children ≥5 years: 300 mg per month via Respirgard II nebulizer (CIII) | ||||
| Atovaquone | |||||
| Children 1 to 3 months and > 24 months: 30 mg per kg orally daily Children 4 to 24 months: 45 mg per kg orally daily (CII) | |||||
| Clindamycin, 20 to 30 mg per kg per day orally in 4 divided doses plus pyrimethamine, 1 mg per kg orally daily plus leucovorin, 5 mg orally every 3 days (BI) | |||||
| Toxoplasma gondii* | Prior toxoplasmic encephalitis | Sulfadiazine, 85 to 120 mg per kg per day orally in 2 to 4 divided doses plus pyrimethamine, 1 mg per kg or 15 mg per m2 (maximum: 25 mg) orally daily plus leucovorin, 5 mg orally every 3 days (AI) | |||
| Mycobacterium avium complex† | Prior disease | Clarithromycin, 7.5 mg per kg (maximum: 500 mg) orally twice daily (AII) plus ethambutol, 15 mg per kg (maximum: 900 mg) orally daily (AII), with or without rifabutin, 5 mg per kg (maximum: 300 mg) orally daily (CII) | Azithromycin, 5 mg per kg (maximum: 250 mg) orally daily (AII) plus ethambutol, 15 mg per kg (maximum: 900 mg) orally daily (AII), with or without rifabutin, 5 mg per kg (maximum: 300 mg) orally daily (CII) | ||
| Cryptococcus neoformans | Documented disease | Fluconazole, 3 to 6 mg per kg orally daily (AII) | Amphotericin B, 0.5 to 1.0 mg per kg IV 1 to 3 times weekly (AI); itraconazole, 2 to 5 mg per kg orally every 12 to 24 hours (BII) | ||
| Histoplasma capsulatum | Documented disease | Itraconazole, 2 to 5 mg per kg orally every 12 to 48 hours (AIII) | Amphotericin B, 1 mg per kg IV weekly (AIII) | ||
| Coccidioides immitis | Documented disease | Fluconazole, 6 mg per kg orally daily (AIII) | Amphotericin B, 1.0 mg per kg IV weekly (AIII); itraconazole, 2 to 5 mg per kg orally every 12 to 48 hours (AIII) | ||
| Cytomegalovirus | Prior end-organ disease | Ganciclovir, 5 mg per kg IV daily or foscarnet, 90 to 120 mg per kg IV daily (AI) | For retinitis: ganciclovir sustained-release implant every 6 to 9 months plus ganciclovir, 30 mg per kg orally three times daily (BIII) | ||
| Salmonella species (non-typhi)§ | Bacteremia | TMP-SMZ, 150/750 mg per m2 in 2 divided doses orally daily for several months (CIII) | Antibiotic chemoprophylaxis with another active agent (CIII) | ||
| II. Recommended only if subsequent episodes are frequent or severe | |||||
| Invasive bacterial infections¶ | > 2 infections in a 1-year period | TMP-SMZ, 150/750 mg per m2, in 2 divided doses orally daily (BI) or IVIG, 400 mg per kg every 2 to 4 weeks (BI) | Antibiotic chemoprophylaxis with another active agent (BIII) | ||
| Herpes simplex virus | Frequent/severe recurrences | Acyclovir, 80 mg per kg in 3 to 4 divided doses orally daily (AII) | |||
| Candida (oropharyngeal) | Frequent/severe recurrences | Fluconazole, 3 to 6 mg per kg orally daily (CIII) | |||
| Candida (esophageal) | Frequent/severe recurrences | Fluconazole, 3 to 6 mg per kg orally daily (BIII) | Itraconazole solution, 5 mg per kg orally daily (CIII); ketoconazole, 5 to 10 mg per kg orally every 12 to 24 hours (CIII) | ||
| Opportunistic illness | Criteria for discontinuing prophylaxis | |||
|---|---|---|---|---|
| Primary | Secondary | Criteria for restarting prophylaxis | ||
| Pneumocystis carinii pneumonia | CD4+ count > 200 cells per mm3 (200 × 106 per L) for >3 to 6 months | No criteria recommended for stopping | Same as criteria for initiating (CIII) | |
| Disseminated Mycobacterium avium complex | CD4+ count > 100 cells per mm3 for > 3 to 6 months; sustained suppression of HIV plasma RNA (CII) | No criteria recommended for stopping | Same as criteria for initiating (CIII) | |
| Toxoplasmosis | No criteria recommended for stopping | No criteria recommended for stopping | Not applicable | |
| Cryptococcosis | Not applicable | No criteria recommended for stopping | Not applicable | |
| Histoplasmosis | Not applicable | No criteria recommended for stopping | Not applicable | |
| Coccidioidomycosis | Not applicable | No criteria recommended for stopping | Not applicable | |
| Cytomegalovirus retinitis | Not applicable | CD4+ count > 100 to 150 per mm3 for > 3 to 6 months | Restart maintenance when CD4+ count < 50 to 100 per mm3 (CIII) | |
| Durable suppression of HIV plasma RNA | ||||
| Non–sight-threatening lesion | ||||
| Adequate vision in contralateral eye | ||||
| Regular ophthalmic examinations (CIII) | ||||
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 × 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 anti-retroviral 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 × 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 ×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 × 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.