In 1995, the U.S. Public Health Service (USPHS) and the Infectious Diseases Society of America (IDSA) developed guidelines for preventing opportunistic infections in persons with human immunodeficiency virus (HIV) infection.1–3 These guidelines, written for health care providers and patients, were revised in 1997 and published in the MMWR,4 Clinical Infectious Diseases,5 the Annals of Internal Medicine,6 American Family Physician,7–9 and Pediatrics10; an accompanying editorial appeared in JAMA.11 Response to these guidelines (e.g., many requests for reprints and observations from health care providers) suggests that they have served as a valuable reference. Because the 1995 and 1997 guidelines included ratings indicating the strength of each recommendation and the quality of supporting evidence, readers were able to assess the relative importance of each recommendation.
Since acquired immunodeficiency syndrome (AIDS) was first recognized nearly 20 years ago, remarkable progress has been made in improving the quality and duration of life of HIV-infected persons. During the first decade of the epidemic, this improvement occurred because of better recognition of opportunistic disease processes, better therapy for acute and chronic complications and the introduction of chemoprophylaxis against Pneumocystis carinii pneumonia (PCP), toxoplasmosis, Mycobacterium avium complex (MAC) disease and bacterial infections. Trimethoprim-sulfamethoxazole was shown to reduce the incidence not only of PCP but also of toxoplasmosis and bacterial infections.
The second decade of the epidemic has witnessed extraordinary progress in developing highly active antiretroviral therapies (HAART) as well as continuing progress in preventing and treating individual opportunistic infections. HAART has reduced the incidence of opportunistic infections and extended life substantially.12 HAART is the most effective approach to preventing opportunistic infections and should be considered for use in all HIV-infected persons who qualify for such therapy. However, some patients are not ready or able to take HAART, and others have tried HAART regimens, but therapy has failed. Such patients will benefit from prophylaxis against opportunistic infections. In addition, prophylaxis against specific opportunistic infections continues to provide survival benefits even among persons who are receiving HAART.13
Because important new data concerning the prevention of opportunistic diseases have emerged since 1997, the USPHS and the IDSA reconvened the Prevention of Opportunistic Infections Working Group on March 4 and 5, 1999, to determine which recommendations warranted revision. Participants included representatives from federal agencies, universities and professional societies, as well as community health care providers and patient advocates. Much attention was focused on recent data related to the advisability of discontinuing opportunistic infection prophylaxis (primary prophylaxis and prophylaxis against recurrence) among persons whose CD4+ T-lymphocyte counts have increased to above prophylaxis thresholds because of HAART. The Opportunistic Infection Working Group also addressed two pathogens not previously considered—human herpesvirus type 8 and hepatitis C virus. In addition, working group members reviewed data concerning the prevention of all common HIV-associated opportunistic infections. In revising these current guidelines, as in earlier editions of the guidelines, the group considered factors such as incidence of disease; severity of disease in terms of morbidity and mortality; level of immunosuppression at which disease is most likely to occur; feasibility, efficacy, and cost of preventive measures; impact of intervention on quality of life; drug toxicities and interactions, and the potential for drug resistance to develop.
During the development of these revised guidelines, working group members reviewed published manuscripts as well as abstracts and material presented at professional meetings if complete manuscripts providing data were available for review. A review of the data that served as the basis for the revisions and additional information discussed at the meeting but not deemed sufficient to justify a revision of the recommendations will be published separately.
Primary Changes in the Recommendations
Primary changes in the disease-specific recommendations include the following:
The addition of statements concerning discontinuation of prophylaxis against specific opportunistic infections when the CD4+ T-lymphocyte count increases in response to HAART.
New recommendations regarding human herpesvirus type 8 and hepatitis C virus infections.
New recommendations concerning injection drug users.
New recommendations about short-course chemoprophylaxis against tuberculosis in HIV-infected persons with positive tuberculin skin tests.
Changes in secondary prophylaxis (chronic maintenance therapy) recommended to prevent the recurrence of MAC and cytomegalovirus disease.
Caution against using fluconazole during pregnancy.
Statements concerning the use of varicella and rotavirus vaccines in HIV-infected infants.
These guidelines, developed by the Opportunistic Infection Working Group, were made available for public comment through announcements in the Federal Register and the MMWR. The final document is endorsed by the USPHS and IDSA, as well as by the Infectious Diseases Society of Obstetrics and Gynecology and the National Foundation for Infectious Diseases.
How to Use the Information in the Guidelines
For each of the 19 diseases covered in this report, specific recommendations are provided that address (1) prevention of exposure to the opportunistic pathogen, (2) prevention of the first episode of disease and (3) prevention of disease recurrence. Although these recommendations were originally published in one document in the MMWR (and are still available from the CDC in that format), the material is divided into three parts for publication in American Family Physician. The first part of the series focuses on the prevention of exposure to opportunistic pathogens. The second and third parts (to be published in the January 15 and February 1, 2000, issues of AFP) will focus on the prevention of disease and the prevention of recurrence of opportunistic infections that commonly occur in patients with HIV.
Each part of the series includes a description of the system used by the USPHS/IDSA to rate the recommendations (Table 1).14 In this system, a letter rating (letters A through E) signifies the strength of the recommendation for or against a preventive modality, and a Roman numeral (numerals I through III) indicates the quality of evidence supporting the recommendation. Additional recommendations advising patients how to prevent exposure to opportunistic pathogens, formatted according to the types of exposure (e.g., occupational, pets, travel) appear in the appendix at the end of this report.
|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.|
This report is oriented toward the prevention of specific opportunistic infections in HIV-infected persons in the United States and other industrialized countries. Recommendations for use of antiretroviral therapy, which is designed to prevent immunologic deterioration and delay the need for many of the chemoprophylactic strategies described in this report, are published elsewhere,12 as are integrated approaches to the care of HIV-infected persons.15
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 for updating these guidelines on a regular basis. The most recent information will be available from the AIDS Treatment Information Service Web site (www.hivatis.org).
Disease-Specific Recommendations for the Prevention of Exposure
PNEUMOCYSTIS CARINII PNEUMONIA
Although some authorities recommend that persons with HIV infection who are at risk for PCP not share a hospital room with a patient who has PCP, data are insufficient to support this recommendation as standard practice (CIII).
HIV-infected persons should be tested for immunoglobulin G (IgG) antibody to Toxoplasma soon after the diagnosis of HIV infection to detect latent infection with Toxoplasma gondii (BIII).
All HIV-infected persons, but particularly those who lack IgG antibody to Toxoplasma, should be counseled about the various sources of toxoplasmic infection. They should be advised not to eat raw or undercooked meat, particularly undercooked pork, lamb or venison (BIII). Specifically, meat should be cooked to an internal temperature of 65.5°C (150°F); meat cooked until it is no longer pink inside generally has an internal temperature of 73.8°C (165°F) and therefore satisfies this requirement.
HIV-infected persons should wash their hands after contact with raw meat and after gardening or other contact with soil; in addition, they should wash fruits and vegetables well before eating them raw (BIII).
If the patient owns a cat, the litter box should be changed daily, preferably by an HIV-negative, nonpregnant person; alternatively, the patient should wash the hands thoroughly after changing the litter box (BIII). Patients should be encouraged to keep their cats inside and not to adopt or handle stray cats (BIII). Cats should be fed only canned or dried commercial food or well-cooked table food, not raw or undercooked meats (BIII). Patients need not be advised to part with their cats or to have their cats tested for toxoplasmosis (EII).
HIV-infected persons should be educated and counseled about the many ways that Cryptosporidium can be transmitted (BIII). Modes of transmission include direct contact with infected adults, diaper-aged children and infected animals; drinking contaminated water; contact with contaminated water during recreational activities; and eating contaminated food.
HIV-infected persons should avoid contact with human and animal feces. They should be advised to wash their hands after contact with human feces (e.g., diaper changing), after handling pets and after gardening or other contact with soil. HIV-infected persons should avoid sexual practices that might result in oral exposure to feces (e.g., oral-anal contact) (BIII).
HIV-infected persons should be advised that newborn and young pets might pose a small risk for transmitting cryptosporidial infection, but they should not be advised to destroy or give away healthy pets. Persons contemplating the acquisition of a new pet should avoid bringing any animal that has diarrhea into their households, should avoid purchasing a dog or cat less than 6 months of age and should not adopt stray pets. HIV-infected persons who wish to assume the small risk for acquiring a puppy or kitten less than 6 months of age should request that their veterinarian examine the animal's stool for Cryptosporidium before they have contact with the animal (BIII). HIV-infected persons should avoid exposure to calves and lambs and to premises where these animals are raised (BII).
HIV-infected persons should not drink water directly from lakes or rivers (AIII).
Waterborne infection also might result from swallowing water during recreational activities. HIV-infected persons should be aware that many lakes, rivers and salt-water beaches and some swimming pools, recreational water parks and ornamental water fountains might be contaminated with human or animal waste that contains Cryptosporidia. They should avoid swimming in water that is likely to be contaminated and should avoid swallowing water while swimming or playing in recreational waters (BIII).
Several outbreaks of cryptosporidiosis have been linked to municipal water supplies. During outbreaks or in other situations in which a community “boil water” advisory is issued, boiling water for one minute will eliminate the risk for cryptosporidiosis (AI).
Use of submicron personal-use water filters (home/office types) and/or bottled water also might reduce the risk (CIII). Only filters capable of removing particles 1 μm in diameter should be considered. (Filters that provide the greatest assurance of oocyst removal include those that operate by reverse osmosis, those labeled as absolute 1-μm filters and those labeled as meeting National Sanitation Foundation [NSF] standard no. 53 for cyst removal. The nominal 1-μm filter rating is not standardized, and many filters in this category might not be capable of removing 99 percent of oocysts.) Sources of bottled water (e.g., wells, springs, municipal tap-water supplies, rivers and lakes) and methods for its disinfection differ; therefore, all brands should not be presumed to be free of cryptosporidial oocysts. Water from wells and springs is much less likely to be contaminated by oocysts than water from rivers or lakes. Treatment of bottled water by distillation or reverse osmosis ensures oocyst removal. Water passed through an absolute 1-μm filter or a filter labeled as meeting NSF standard no. 53 for cyst removal before bottling will provide nearly the same level of protection. Use of nominal 1-μm filters by bottlers as the only barrier to Cryptosporidia might not result in the removal of 99 percent of oocysts.
The magnitude of the risk for acquiring cryptosporidiosis from drinking water in a nonoutbreak setting is uncertain, and current data are inadequate to recommend that all HIV-infected persons boil water or avoid drinking tap water in nonoutbreak settings.
However, HIV-infected persons who wish to take independent action to reduce the risk for waterborne cryptosporidiosis may choose to take precautions similar to those recommended during outbreaks. Such decisions should be made in conjunction with health care providers. Persons who opt for a personal-use filter or bottled water should be aware of the complexities involved in selecting appropriate products, the lack of enforceable standards for the destruction or removal of oocysts, the cost of the products and the logistic difficulty of using these products consistently.
Patients who take precautions to avoid acquiring cryptosporidiosis from drinking water should be advised that ice made from contaminated tap water also can be a source of infection (BII). Such persons also should be aware that fountain beverages served in restaurants, bars, theaters and other places might pose a risk because these beverages, as well as the ice they contain, are made from tap water. Nationally distributed brands of bottled or canned carbonated soft drinks are safe to drink. Commercially packaged noncarbonated soft drinks and fruit juices that do not require refrigeration until after they are opened (i.e., those that can be stored unrefrigerated on grocery shelves) also are safe. Nationally distributed brands of frozen fruit juice concentrate are safe if they are reconstituted by the user with water from a safe source. Fruit juices that must be kept refrigerated from the time they are processed to the time of consumption might be fresh (unpasteurized) or heat-treated (pasteurized); only those juices labeled as pasteurized should be considered free of risk from Cryptosporidium. Other pasteurized beverages and beers are considered safe to drink (BII). No data are available concerning survival of Cryptosporidia oocysts in wine.
HIV-infected persons should avoid eating raw oysters because cryptosporidial oocysts can survive in oysters for more than two months and have been found in oysters taken from some commercial oyster beds (BIII). Cryptosporidia-infected patients should not work as food handlers, especially if the food to be handled is intended to be eaten without cooking (BII). Because most foodborne outbreaks of cryptosporidiosis are believed to have been caused by infected food handlers, more specific recommendations to avoid exposure to contaminated food cannot be made.
In a hospital, standard precautions (i.e., use of gloves and hand washing after removal of gloves) should be sufficient to prevent transmission of cryptosporidiosis from an infected patient to a susceptible HIV-infected person (BII). However, because of the potential for fomite transmission, some experts recommend that HIV-infected persons, especially those who are severely immunocompromised, should not share a room with a patient with cryptosporidiosis (CIII).
Other than general attention to hand washing and other personal hygiene measures, no precautions to reduce exposure can be recommended at this time.
HIV-infected persons should be advised that certain activities and occupations might increase the likelihood of exposure to tuberculosis (BIII). These include volunteer work or employment in health care facilities, correctional institutions and shelters for the homeless, as well as other settings identified as high risk by local health authorities. Decisions about whether to continue with activities in these settings should be made in conjunction with the health-care provider and should be based on factors such as the patient's specific duties in the workplace, the prevalence of tuberculosis in the community and the degree to which precautions are taken to prevent the transmission of tuberculosis in the workplace (BIII). Whether the patient continues with such activities might affect the frequency with which screening for tuberculosis should be conducted.
DISSEMINATED INFECTION WITH MYCOBACTERIUM AVIUM COMPLEX
MAC organisms are common in environmental sources such as food and water. Current information does not support specific recommendations regarding avoidance of exposure.
BACTERIAL RESPIRATORY INFECTIONS
Because Streptococcus pneumoniae and Haemophilus influenzae are common in the community, no effective way exists to reduce exposure to these bacteria.
BACTERIAL ENTERIC INFECTIONS
Food-Related Exposure. Health care providers should advise HIV-infected persons not to eat raw or undercooked eggs (including foods that might contain raw eggs [e.g., some preparations of hollandaise sauce, Caesar and other salad dressings, and mayonnaise]); raw or undercooked poultry, meat, or seafood; or unpasteurized dairy products. Poultry and meat should be well cooked and should not be pink in the middle (an internal temperature greater than 73.8°C [165°F]). Produce should be washed thoroughly before being eaten (BIII).
Health care providers should advise HIV-infected persons to avoid cross-contamination of foods. Uncooked meats should not come into contact with other foods. Hands, cutting boards, counters, knives and other utensils should be washed thoroughly after contact with uncooked foods (BIII).
Health-care providers should advise HIV-infected persons that, although the incidence of listeriosis is low, it is a serious disease that occurs with unusually high frequency among HIV-infected persons who are severely immunosuppressed. Such persons may choose to avoid soft cheeses because some studies have shown an association between these foods and listeriosis. These studies also have documented an association between ready-to-eat foods (e.g., hot dogs and cold cuts from delicatessen counters) and listeriosis. An immunosuppressed, HIV-infected person who wishes to reduce the risk for foodborne disease as much as possible may choose to reheat such foods until they are steaming hot before eating them (CIII).
Pet-Related Exposure. When obtaining a new pet, HIV-infected persons should avoid animals less than 6 months of age, especially those that have diarrhea (BIII).
HIV-infected persons should avoid contact with animals that have diarrhea (BIII). HIV-infected pet owners should seek veterinary care for animals with diarrheal illness, and a fecal sample from such animals should be examined for Cryptosporidium, Salmonella and Campylobacter.
HIV-infected persons should wash their hands after handling pets (especially before eating) and should avoid contact with pets' feces (BIII).
HIV-infected persons should avoid contact with reptiles (e.g., snakes, lizards, iguanas and turtles) because of the risk for salmonellosis (BIII).
Travel-Related Exposure. The risk for foodborne and waterborne infections among immunosuppressed, HIV-infected persons is magnified during travel to developing countries. Persons who travel to such countries should avoid foods and beverages that might be contaminated, particularly raw fruits and vegetables, raw or undercooked seafood or meat, tap water, ice made with tap water, unpasteurized milk and dairy products, and items sold by street vendors (AII). Foods and beverages that are generally safe include steaming-hot foods, fruits that are peeled by the traveler, bottled (especially carbonated) beverages, hot coffee and tea, beer, wine and water brought to a rolling boil for one minute (AII). Treatment of water with iodine or chlorine might not be as effective as boiling but can be used when boiling is not practical (BIII).
INFECTION WITH BARTONELLA (FORMERLY ROCHALIMAEA)
HIV-infected persons, particularly those who are severely immunosuppressed, are at unusually high risk for developing relatively severe disease related to infection with Bartonella species, which can be transmitted from cats. These persons should consider the potential risks of cat ownership (CIII). Persons who acquire a cat should adopt or purchase an animal more than one year of age and in good health (BII).
Although declawing is not generally advised, HIV-infected persons should avoid rough play with cats and situations in which scratches are likely (BII). Any cat-associated wound should be washed promptly (CIII). HIV-infected persons should not allow cats to lick open wounds or cuts (BIII).
Care of cats should include flea control (CIII). No evidence indicates any benefits to cats or their owners from routine culture or serologic testing of the pet for Bartonella infection (DII).
Candida organisms are common on mucosal surfaces and skin. No measures are available to reduce exposure to these fungi.
HIV-infected persons cannot completely avoid exposure to Cryptococcus neoformans. No evidence shows that exposure to pigeon droppings is associated with an increased risk for acquiring cryptococcosis.
Although HIV-infected persons living in or visiting histoplasmosis-endemic areas cannot completely avoid exposure to Histoplasma capsulatum, those whose CD4+ T-lymphocyte cell counts are less than 200 per mm3 (200 × 106 per L) should avoid activities known to be associated with increased risk (e.g., creating dust when working with surface soil; cleaning chicken coops that are heavily contaminated with droppings; disturbing soil beneath bird-roosting sites; cleaning, remodeling or demolishing old buildings; and exploring caves) (CIII).
Although HIV-infected persons living in or visiting areas in which coccidioidomycosis is endemic cannot completely avoid exposure to Coccidioides immitis, they should, when possible, avoid activities associated with increased risk (e.g., those involving extensive exposure to disturbed native soil, for example, at building excavation sites or during dust storms) (CIII).
HIV-infected persons who belong to risk groups with relatively low rates of seropositivity for cytomegalovirus (CMV) and who therefore cannot be presumed to be seropositive should be tested for antibody to CMV (BIII). These groups include patients who have not had male homosexual contact or used injection drugs.
HIV-infected adolescents and adults should be advised that CMV is shed in semen, cervical secretions and saliva, and that latex condoms must always be used during sexual contact to reduce the risk for exposure to CMV and to other sexually transmitted pathogens (AII).
HIV-infected adults and adolescents who are child care providers or parents of children in child care facilities should be informed that they are at increased risk for acquiring CMV infection (BI). Similarly, parents and other caretakers of HIV-infected children should be advised of the increased risk to children at these centers (BIII). The risk for acquiring CMV infection can be diminished by good hygienic practices such as hand washing (AII).
HIV-exposed infants and HIV-infected children, adolescents and adults who are seronegative for CMV and require blood transfusion should be administered only CMV antibody-negative or leukocyte-reduced cellular blood products in nonemergency situations (BIII).
HERPES SIMPLEX VIRUS DISEASE
HIV-infected persons should use latex condoms during every act of sexual intercourse to reduce the risk for exposure to herpes simplex virus (HSV) and other sexually transmitted pathogens (AII). They should specifically avoid sexual contact when herpetic lesions (genital or orolabial) are evident (AII).
VARICELLA-ZOSTER VIRUS INFECTION
HIV-infected children and adults who are susceptible to varicella-zoster virus (VZV) (i.e., those who have no history of chickenpox or shingles, or are seronegative for VZV) should avoid exposure to persons with chickenpox or shingles (AII).
Household contacts (especially children) of susceptible HIV-infected persons should be vaccinated against VZV if they have no history of chickenpox and are seronegative for HIV, so that they will not transmit VZV to their susceptible HIV-infected contacts (BIII).
HUMAN HERPESVIRUS 8 INFECTION
The mechanism of transmitting human herpesvirus 8 (HHV-8), the herpesvirus associated with Kaposi's sarcoma, is not known. Epidemiologic evidence suggests that sexual transmission is likely among men who have sex with men and can occur among heterosexuals as well. However, the virus has been detected more frequently in saliva than in semen from HHV-8-seropositive HIV-infected persons. Although the efficacy of condom use in preventing HHV-8 infection has not been established, HIV-infected persons should use latex condoms during every act of sexual intercourse to reduce the risk for exposure to sexually transmitted pathogens (AII).
HUMAN PAPILLOMAVIRUS INFECTION
HIV-infected persons should use latex condoms during every act of sexual intercourse to reduce the risk for exposure to sexually transmitted pathogens (AII), although little evidence exists to suggest that condoms reduce the risk for infection with human papillomavirus.
HEPATITIS C VIRUS INFECTION
The chief route of hepatitis C virus (HCV) transmission in the United States is injection drug use. Because injection drug use is a complex behavior, clinicians should assess the individual patient's readiness to change this practice and encourage efforts to provide patient education and support directed at recovery.
Stop using injection drugs (AIII).
Enter and complete a substance-abuse treatment program, including a relapse prevention program (AIII).
If they continue to inject drugs, patients should be advised (BIII) to do the following:
Never reuse or share syringes, needles, water or drug preparation equipment; if injection equipment that has been used by other persons is shared, first clean the equipment with bleach and water as is recommended for prevention of HIV; use only sterile syringes obtained from a reliable source (e.g., pharmacies or syringe exchange programs).
Use sterile (e.g., boiled) water to prepare drugs; if this is not possible, use clean water from a reliable source (e.g., fresh tap water).
Use a new or disinfected container (“cooker”) and a new filter (“cotton”) to prepare drugs.
Clean the injection site with a new alcohol swab before injection.
Safely dispose of syringes after one use.
If patients continue to use illegal drugs intranasally (“snorting”), they should be advised (BIII) to do the following:
Be aware that this practice has been associated with HCV transmission.
Not share equipment (e.g., straws) with other users.
Persons considering tattooing or body piercing should be informed of potential risks of acquiring bloodborne infections, which could be transmitted if equipment is not sterile or if proper infection control procedures are not followed (e.g., washing hands, using latex gloves and cleaning and disinfecting surfaces) (BIII).18
To reduce risks for acquiring bloodborne infections, patients should be advised not to share dental appliances, razors or other personal care articles (BIII).
Although the efficiency of sexual transmission of HCV remains controversial, safe sexual practices should be encouraged, and barrier precautions (e.g., latex condoms) are recommended to reduce the risk for exposure to sexually transmitted pathogens (AII).