PREVENTION OF OPPORTUNISTIC INFECTIONS

1. PREVENTION OFOPPORTUNISTIC INFECTIONS 3 Feb 2009 J Caperna, MD UCSD Owen Clinic

2. Goals of lecture: At the end of the session, the participant will be able to: 3) Know the most frequently occurring OI’s, their environmental distribution, routes of exposure & how to prevent them.

3. Goals of lecture: At the end of the session, the participant will be able to: 4) Discuss tuberculosis exposure; 5) Understand the public health principles used to recommend prophylaxis; 6) Identify indications for primary or secondary prophylaxis. .

4. Tuberculosis The most common opportunistic infection in AIDS patients worldwide. A common cause of death in AIDS patients worldwide. After aggressive prevention efforts including treatment of latent asymptomatic tuberculosis infection, the incidence of TB in the United States fell dramatically through the 1980’s, until incidence increased related to AIDS. Today, over half of TB cases in the US are in immigrants. Intensive Prevention Efforts are still needed in the US in immigrants and AIDS patients, which account for the majority of cases. Prevention is effective only with adequate resources.

5. Importance of Preventing TB Estimate in general that 1 active TB patient will infect 10 others. TB outbreaks can be huge, in the 100’s or more. Recent South African example showed that 47 patients were potentially infected by the same person. Treatment is long, 6-12 months. Rare cases now of XDR-TB that are untreatable.

6. Goals of lecture: At the end of the session, the participant will be able to: 1) Define Opportunistic Infection (OI); 2) State the associated disease states in which OI’s occur;

7. Prevention of OI’sOUTLINE 1) Definition of OI 2) Prevention of Exposure to OI 3) Primary & Secondary Prophylaxis of OI’s 4) CDC guidelines

8. Define: OPPORTUNISTIC INFECTION

9. An infection by a microorganism that normally does not cause disease but becomes pathogenic when the body’s immune system is impaired.

10. Wikepedia “…infections caused by organisms that usually do not cause disease in a person with a healthy immune system, but can affect people with a poorly functioning or suppressed immune system. They need an ‘opportunity’ to infect a person.”

11. Case Definition Definition based on a list of cases. Each disease or a cluster of some of them defines the condition. For AIDS, the CDC has a “case” definition, with a list of over 12 infections considered to be opportunistic if associated with HIV infection.

12. The 1993 AIDS Surveillance Case Definition of the U.S. Centers for Disease Control and Prevention A diagnosis of AIDS is made whenever a person is HIV-positive and: 1) he or she has a CD4+ cell count below 200 cells per microliter OR 2) his or her CD4+ cells account for fewer than 14 percent of all lymphocytes OR 3) that person has been diagnosed with one or more of the AIDS-defining illnesses listed below.

13. AIDS-Defining Illnesses Candidiasis of bronchi, trachea, or lungs (see Fungal Infections) Candidiasis, esophageal (see Fungal Infections) Cervical cancer, invasive--HPV Coccidioidomycosis, disseminated (see Fungal Infections) Cryptococcosis, extrapulmonary (see Fungal Infections) Cryptosporidiosis, chronic intestinal (>1 month duration) (see Enteric Diseases) Cytomegalovirus disease (other than liver, spleen, or lymph nodes) Cytomegalovirus retinitis (with loss of vision) Encephalopathy, HIV-related† (see Dementia) Herpes simplex: chronic ulcer(s) (>1 month duration) or bronchitis, pneumonitis, or esophagitis Histoplasmosis, disseminated (see Fungal Infections) Isosporiasis, chronic intestinal (>1 month duration) (see Enteric Diseases) Kaposi's sarcoma, HHV8 Lymphoma, Burkitt's, EBV Lymphoma, immunoblastic Lymphoma, primary, of brain (primary central nervous system lymphoma) Mycobacterium avium complex or disease caused by M. Kansasii, disseminated Disease caused by Mycobacterium tuberculosis, any site (pulmonary‡ or extrapulmonary†) (see Tuberculosis) Disease caused by Mycobacterium, other species or unidentified species, disseminated Pneumocystis carinii pneumonia (aka jiroveci) Pneumonia, recurrent‡ (see Bacterial Infections) Progressive multifocal leukoencephalopathy Salmonella septicemia, recurrent (see Bacterial Infections) Toxoplasmosis of brain (encephalitis) Wasting syndrome caused by HIV infection†

14. OI’s by Kingdom Bacteria (MONERA) Salmonella Mycobacteria TB, MAC, Kansasii, other Pneumococcus Fungi (FUNGI) Candida Crytpococcus Coccidiomycosis Histoplasmosis Pneumocystis Protozoa/parasites (PROTISTA) Toxoplasmosis Cryptosporidium Isospera

15. OI’s by Kingdom Viruses (perhaps not living, and not in any kingdom) CMV HSV

16. Infections more frequent and more severe in HIV, but not in case definition of AIDS: Hep B Hep C HHV8 HPV EBV Syphilis

17. Additional Illnesses That Are AIDS-Defining in Children, But Not Adults Multiple, recurrent bacterial infections Lymphoid interstitial pneumonia/pulmonary lymphoid hyperplasia

18. Conditions of Suppressed Immunity other than AIDS: 1) Malnutrition 2) Immunosuppressive agents used for organ transplant 3) Prednisone 4) Chemotherapy for cancer 5) Genetic predisposition 6) Antibiotic treatment 7) Skin damage 8) Medical procedure

19. Primary Immunodeficiency Diseases  1. Genetic conditions associated with immune disorders. 2. Congenital versus acquired. Deficiencies: a. Cellular b. Humeral c. Phagocytic d. Complement e. Combined f. Other

20. Primary Immunodeficiency Diseases  1)Severe Combined Immunodeficiency, or SCID 2) X-Linked Agammaglobulinemia (XLA) 3) Common Variable Immunodeficiency 4) Selective IgA Deficiency 5) IgG Subclass Deficiency 6) Hyper IgM Syndrome 7) DiGeorge Syndrome 8) Hereditary Ataxia-Telangectasia 9) Wiskott-Aldrich Syndrome 10) Phagocytic Deficiencies 11) Chronic Granulomatous Disease (CGD) 12) Chediak-Higashi Syndrome 13) Complement Deficiencies 14) Hyper IgE Syndrome (Job Syndrome)

21. Prevention of OI’sOUTLINE 1) Definition of OI 2) Prevention of Exposure to OI 3) Primary & Secondary Prophylaxis of OI’s 4) CDC guidelines

22. Types of Exposure Airborne Waterborne Foodborne Sexual Bloodborne Environmental/Occupational Pet-related Travel-related 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 to avoid eating raw or undercooked meat (BIII). 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 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 to avoid eating raw or undercooked meat (BIII). 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).

23. 2001 USPHS/IDSA Guidelines for the Prevention of Opportunistic Infections in Persons Infected With Human Immunodeficiency Virus

24. 2002 MMWR June 14, /51(RR08); 47-52. Appendix: “Recommendations To Help Patients Avoid Exposure to or Infection from Opportunistic Pathogens”

25. Prevention of Exposure-no recommendations Currently, there are no recommendations for preventing exposure to: P jiroveci pneumonia (PCP) – no data to support isolation M avium complex (MAC) – no data S pneumoniae and H influenzae – not practical Candidiasis – not practical Cryptococcosis – not practical Although some authorities recommend that persons with human immunodeficiency virus (HIV) infection who are at risk for P jiroveci pneumonia (PCP) not share a hospital room with a patient who has PCP, data are insufficient to support this recommendation as standard practice (CIII). Organisms of the M avium complex (MAC) are common in environmental sources such as food and water. Current information does not support specific recommendations regarding avoidance of exposure. Because Streptococcus pneumoniae and Haemophilus influenzae are common in the community, no effective way exists to reduce exposure to these bacteria. 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 exists that exposure to pigeon droppings is associated with an increased risk for acquiring cryptococcosis. Although some authorities recommend that persons with human immunodeficiency virus (HIV) infection who are at risk for P jiroveci pneumonia (PCP) not share a hospital room with a patient who has PCP, data are insufficient to support this recommendation as standard practice (CIII). Organisms of the M avium complex (MAC) are common in environmental sources such as food and water. Current information does not support specific recommendations regarding avoidance of exposure. Because Streptococcus pneumoniae and Haemophilus influenzae are common in the community, no effective way exists to reduce exposure to these bacteria. 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 exists that exposure to pigeon droppings is associated with an increased risk for acquiring cryptococcosis.

26. Pathogens for which recommendations exist for prevention of exposure EXAMPLES Airborne: Tuberculosis, Histoplasmosis, Coccidiomycosis Waterborne: Cryptosporidium, isospera Foodborne: Toxoplasmosis, enteric bacteria Blood/Sexual: Hepatitis C, Hep B, Syphilis, HPV, Cytomegalovirus (CMV), Herpes Simples Virus (HSV) Pets: toxoplasmosis (in cats) 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 to avoid eating raw or undercooked meat (BIII). 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 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 to avoid eating raw or undercooked meat (BIII). 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).

27. Toxoplasmosis Test for Toxoplasma IgG antibody soon after diagnosis of HIV infection to detect latent infection Counsel all HIV-positive persons, particularly if IgG Ab negative, to avoid the various sources of toxoplasmic infection, including food, pet, soil exposures 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 to avoid eating raw or undercooked meat (BIII). 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 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 to avoid eating raw or undercooked meat (BIII). 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).

28. Cryptosporidiosis Educate and counsel HIV-infected persons about transmission of Cryptosporidium: Contact with infected adults and children Contact with infected animals Drinking or contact with contaminated water (eg, water from lakes, rivers) Drinking contaminated public water supplies Eating contaminated food Wash hands after gardening or soil contact, risk of cryptosporidium, toxoplasmosis. HIV-infected persons should be counseled about Cryptosporidium transmission (BIII), including: having direct contact with infected adults, diaper-aged children, and infected animals; drinking contaminated water; coming into contact with contaminated water during recreational activities; and eating contaminated food. HIV-infected persons should avoid contact with human and animal feces and should wash their hands after contact with human feces (eg, diaper changing), after handling pets, and after gardening or other contact with soil. Sexual practices that might result in oral exposure to feces should be avoided (BIII). Newborn and very young pets might pose a small risk for transmitting cryptosporidial infection, but they should not be advised to destroy or give away healthy pets. Avoid: acquisition of a new pet that has diarrhea, purchasing a dog or cat aged less than 6 months, adopting stray pets, and exposure to calves, lambs, and premises where these animals are raised (BII).  Water. Avoid: drinking of or contact with water in lakes, rivers, salt-water beaches, some swimming pools, water parks, ornamental water fountains (BIII), drinking municipal water supplies during outbreaks or in other situations in which a community "boil-water" advisory is issued. Ice made from contaminated tap water also can be a source of infection (BII). Bottled or canned commercially packaged soft drinks and fruit juices that do not require refrigeration until after they are opened are safe to drink, as are nationally distributed brands of frozen fruit juice concentrate if they are reconstituted with safe water. Use only fruit juices that must be kept refrigerated if they were heat-treated (pasteurized). Other pasteurized beverages and beers also are considered safe to drink (BII). No data are available concerning survival of Cryptosporidium oocysts in wine. Because most food-borne outbreaks of cryptosporidiosis are believed to have been caused by infected food handlers, specific recommendations to avoid exposure to contaminated food cannot be made. However, eating raw oysters should be avoided because cryptosporidial oocysts can survive in oysters for more than 2 months and have been found in oysters taken from some commercial oyster beds (BIII). Cryptosporidium-infected patients should not work as food handlers, especially if the food to be handled is intended to be eaten without cooking (BII). HIV-infected persons should be counseled about Cryptosporidium transmission (BIII), including: having direct contact with infected adults, diaper-aged children, and infected animals; drinking contaminated water; coming into contact with contaminated water during recreational activities; and eating contaminated food. HIV-infected persons should avoid contact with human and animal feces and should wash their hands after contact with human feces (eg, diaper changing), after handling pets, and after gardening or other contact with soil. Sexual practices that might result in oral exposure to feces should be avoided (BIII). Newborn and very young pets might pose a small risk for transmitting cryptosporidial infection, but they should not be advised to destroy or give away healthy pets. Avoid: acquisition of a new pet that has diarrhea, purchasing a dog or cat aged less than 6 months, adopting stray pets, and exposure to calves, lambs, and premises where these animals are raised (BII).  Water. Avoid: drinking of or contact with water in lakes, rivers, salt-water beaches, some swimming pools, water parks, ornamental water fountains (BIII), drinking municipal water supplies during outbreaks or in other situations in which a community "boil-water" advisory is issued. Ice made from contaminated tap water also can be a source of infection (BII). Bottled or canned commercially packaged soft drinks and fruit juices that do not require refrigeration until after they are opened are safe to drink, as are nationally distributed brands of frozen fruit juice concentrate if they are reconstituted with safe water. Use only fruit juices that must be kept refrigerated if they were heat-treated (pasteurized). Other pasteurized beverages and beers also are considered safe to drink (BII). No data are available concerning survival of Cryptosporidium oocysts in wine. Because most food-borne outbreaks of cryptosporidiosis are believed to have been caused by infected food handlers, specific recommendations to avoid exposure to contaminated food cannot be made. However, eating raw oysters should be avoided because cryptosporidial oocysts can survive in oysters for more than 2 months and have been found in oysters taken from some commercial oyster beds (BIII). Cryptosporidium-infected patients should not work as food handlers, especially if the food to be handled is intended to be eaten without cooking (BII).

29. Bacterial Enteric Infections Food Do not eat raw or undercooked eggs, raw or undercooked poultry, meat, seafood,sushi and other high-risk foods 180 F for poultry, 165 F for red meat. Avoid soft cheeses, meat pates and cold deli items Avoid salad bars Avoid cross-contamination of foods and wash hands after preparation Health care providers should advise HIV-infected persons not to eat raw or undercooked eggs (including foods that might contain raw eggs, such as some preparations of hollandaise sauce, Caesar and certain other salad dressings, some mayonnaises, uncooked cookie and cake batter, eggnog); raw or undercooked poultry, meat, seafood (especially raw shellfish); unpasteurized dairy products; unpasteurized fruit juices; and raw seed sprouts (eg, alfalfa sprouts, mung bean sprouts). Poultry and meat are safest when adequate cooking is confirmed with a thermometer (internal temperature of 180º F for poultry and 165º F for red meats). If a thermometer is not used, the risk of illness is decreased by consuming poultry and other meats that have no trace of pink color. Color change of the meat (eg, absence of pink) does not always correlate with internal temperature (BIII). 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 (including hot dogs) and their juices 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 severely immunosuppressed HIV-infected persons. An immunosuppressed, HIV-infected person who wishes to reduce the risk of acquiring listeriosis as much as possible may choose to do the following (CIII): a) Avoid soft cheeses (eg, feta, Brie, Camembert, blue-veined and Mexican-style cheese such as queso fresco). Hard cheeses, processed cheeses, cream cheese (including slices and spreads), cottage cheese, and yogurt need not be avoided. b) Cook leftover foods or ready-to-eat foods (eg, hot dogs) until steaming hot before eating. c) Avoid foods from delicatessen counters (eg, prepared salads, meats, cheeses) or heat/reheat these foods until steaming before eating. d) Avoid refrigerated pates and other meat spreads, or heat/reheat these foods until steaming. Canned or shelf-stable pate and meat spreads need not be avoided. e) Avoid raw or unpasteurized milk (including goat’s milk) and milk products, as well as foods that contain unpasteurized milk or milk products (CIII).Health care providers should advise HIV-infected persons not to eat raw or undercooked eggs (including foods that might contain raw eggs, such as some preparations of hollandaise sauce, Caesar and certain other salad dressings, some mayonnaises, uncooked cookie and cake batter, eggnog); raw or undercooked poultry, meat, seafood (especially raw shellfish); unpasteurized dairy products; unpasteurized fruit juices; and raw seed sprouts (eg, alfalfa sprouts, mung bean sprouts). Poultry and meat are safest when adequate cooking is confirmed with a thermometer (internal temperature of 180º F for poultry and 165º F for red meats). If a thermometer is not used, the risk of illness is decreased by consuming poultry and other meats that have no trace of pink color. Color change of the meat (eg, absence of pink) does not always correlate with internal temperature (BIII). 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 (including hot dogs) and their juices 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 severely immunosuppressed HIV-infected persons. An immunosuppressed, HIV-infected person who wishes to reduce the risk of acquiring listeriosis as much as possible may choose to do the following (CIII): a) Avoid soft cheeses (eg, feta, Brie, Camembert, blue-veined and Mexican-style cheese such as queso fresco). Hard cheeses, processed cheeses, cream cheese (including slices and spreads), cottage cheese, and yogurt need not be avoided. b) Cook leftover foods or ready-to-eat foods (eg, hot dogs) until steaming hot before eating. c) Avoid foods from delicatessen counters (eg, prepared salads, meats, cheeses) or heat/reheat these foods until steaming before eating. d) Avoid refrigerated pates and other meat spreads, or heat/reheat these foods until steaming. Canned or shelf-stable pate and meat spreads need not be avoided. e) Avoid raw or unpasteurized milk (including goat’s milk) and milk products, as well as foods that contain unpasteurized milk or milk products (CIII).

30. Bacterial Enteric Infections Pets Avoid: new pets <6 months old, especially those that have diarrhea contact with animals that have diarrhea contact with pets' feces contact with reptiles, chicks, and ducklings because of the risk for salmonellosis Bird feces has cryptococcus, histoplasmosis, mai Cats feces carries toxoplasmosis, Cat scratch can transmit Bartonella Wash hands after handling pets When obtaining a new pet, HIV-infected persons should avoid animals aged less than 6 months, 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 (eg, snakes, lizards, iguanas, and turtles) as well as chicks and ducklings because of the risk for salmonellosis (BIII). When obtaining a new pet, HIV-infected persons should avoid animals aged less than 6 months, 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 (eg, snakes, lizards, iguanas, and turtles) as well as chicks and ducklings because of the risk for salmonellosis (BIII).

31. Bacterial Enteric Infections Travel The risk for food/water-borne infections is higher during travel to developing countries Avoid high-risk foods and beverages: raw foods, tap water, items sold by street vendors Generally safe: steaming-hot foods and beverages, fruits that are peeled by the traveler, and bottled beverages Boil water; use iodine or chlorine when boiling is not practical 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, beer, and wine, hot coffee and tea, and water brought to a rolling boil for 1 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). 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, beer, and wine, hot coffee and tea, and water brought to a rolling boil for 1 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).

32. Histoplasmosis Exposure in histoplasmosis-endemic areas cannot be avoided completely Patients with CD4 counts <200 cells/µL should avoid risky activities (eg, contact with dusty surface soil, chicken coops) Prevention of Exposure Although HIV-infected persons living in or visiting histoplasmosis-endemic areas cannot completely avoid exposure to Histoplasma capsulatum, those whose CD4 counts are <200 cells/µL should avoid activities known to be associated with increased risk, such as 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).Prevention of Exposure Although HIV-infected persons living in or visiting histoplasmosis-endemic areas cannot completely avoid exposure to Histoplasma capsulatum, those whose CD4 counts are <200 cells/µL should avoid activities known to be associated with increased risk, such as 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).

33. Cytomegalovirus Disease Persons in risk groups with low rates of CMV seropositivity should be tested for antibody Counsel on consistent condom use Counsel on risk of transmission from children CMV-seronegative persons requiring blood transfusion should be given only CMV antibody-negative or leukocyte-reduced cellular blood products in nonemergency situations Prevention of Exposure 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 handwashing (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).Prevention of Exposure 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 handwashing (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).

34. Herpes Simplex Virus Consistent use of condoms to reduce risk of sexual exposure Prevention of Exposure 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).Prevention of Exposure 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).

35. Varicella-Zoster Virus If susceptible to VZV, avoid exposure to persons with zoster Immunize household contacts of HIV-positive persons Prevention of Exposure HIV-infected children and adults who are susceptible to varicella-zoster virus (VZV), including 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). Prevention of Exposure HIV-infected children and adults who are susceptible to varicella-zoster virus (VZV), including 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). 

36. Human Herpesvirus 8 Infection(Kaposi Sarcoma-Associated Herpes Virus) Counsel about deep kissing and sexual intercourse with high-risk persons Consistent use of condoms during sex Do not share IV drug equipment Prevention of Exposure Persons coinfected with HIV and HHV-8 are at risk for developing Kaposi sarcoma (KS), and there is evidence that progression to KS may be accelerated in individuals who seroconvert to HHV-8 after being infected with HIV. Thus it is important to prevent acquisition of HHV-8 infections in those already infected with HIV. The 3 major routes of HHV-8 transmission appear to be oral (the virus infects oral epithelial cells, and infection has been associated with deep kissing in one study), via semen (HHV-8 is detected less frequently in semen than in saliva), and through blood via needle sharing. Patients should be counseled that deep kissing and sexual intercourse with individuals who have high risk of being infected with HHV-8, including persons who have KS or who are infected with HIV, may lead to acquisition of the agent that causes KS (CIII). Although the efficacy of condom use for preventing HHV-8 exposure has not been established, HIV-infected persons should use latex condoms during every act of sexual intercourse to reduce exposure to sexually transmitted pathogens (AII). HIV-infected injection drug users should be counseled to not share drug injection equipment, even if both users are already HIV infected, because of the chance of becoming infected with HHV-8 or other bloodborne pathogens (BIII).Prevention of Exposure Persons coinfected with HIV and HHV-8 are at risk for developing Kaposi sarcoma (KS), and there is evidence that progression to KS may be accelerated in individuals who seroconvert to HHV-8 after being infected with HIV. Thus it is important to prevent acquisition of HHV-8 infections in those already infected with HIV. The 3 major routes of HHV-8 transmission appear to be oral (the virus infects oral epithelial cells, and infection has been associated with deep kissing in one study), via semen (HHV-8 is detected less frequently in semen than in saliva), and through blood via needle sharing. Patients should be counseled that deep kissing and sexual intercourse with individuals who have high risk of being infected with HHV-8, including persons who have KS or who are infected with HIV, may lead to acquisition of the agent that causes KS (CIII). Although the efficacy of condom use for preventing HHV-8 exposure has not been established, HIV-infected persons should use latex condoms during every act of sexual intercourse to reduce exposure to sexually transmitted pathogens (AII). HIV-infected injection drug users should be counseled to not share drug injection equipment, even if both users are already HIV infected, because of the chance of becoming infected with HHV-8 or other bloodborne pathogens (BIII).

37. Human Papillomavirus Infection Consistent use of condoms during sex. Recently, some evidence that this reduces risk for HPV. Prevention of Exposure 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 there is little evidence to suggest that condoms reduce the risk for infection with human papillomavirus (HPV).Prevention of Exposure 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 there is little evidence to suggest that condoms reduce the risk for infection with human papillomavirus (HPV).

38. Prevention of OI’sOUTLINE 1) Definition of OI 2) Prevention of Exposure to OI 3) Prevention Despite or After Exposure:Primary & Secondary Prophylaxis of OI’s 4) CDC guidelines

39. Principles to guide prophylaxis recommendations: Environmental distribution, Settings where exposure cannot be prevented, Existence of effective prophylaxis, Toxicity of prophylaxis, Feasibility of prophylaxis (injections, meds by mouth, duration) Cost of prophylaxis.

40. Two types of prophylaxis: PRIMARY SECONDARY

41. Two types of prophylaxis: PRIMARY---to prevent even first occurrence of infection. SECONDARY— to prevent a second occurrence of an infection that has already occurred at least once.

42. Prevention of OI’sOUTLINE 1) Definition of OI 2) Prevention of Exposure to OI 3) Primary & Secondary Prophylaxis of OI’s 4) CDC guidelines

43. 2004 CDC guidelines Treating Opportunistic Infections Among HIV-infected Adults and Adolescents. MMWR 53 (RR15), pp 1-112.

44. Summary of OIs for Which Prevention Is Recommended Primary Prophylaxis Pneumocystis jiroveci pneumonia (PCP)* Tuberculosis* Toxoplasmosis* Mycobacterium avium complex (MAC)* Varicella-zoster* S pneumoniae infections† Hepatitis A and B† Influenza†

45. Summary of OIs for Which Prevention Is Recommended Secondary Prophylaxis Pneumocystis jiroveci pneumonia (PCP)* Toxoplasmosis* Mycobacterium avium complex (MAC)* Cryptococcosis* Histoplasmosis* Coccidioidomycosis* Cytomegalovirus* Salmonella bacteremia†

46. PRIMARY Prophylaxis for Opportunistic Infections WHEN TO START? CD4<200 PCP CD4<100 Toxoplasmosis CD4<50 MAC

47. What are the diseases we are trying to prevent? Pictures of pathogens and pathology. Three of the most common OI’s in AIDS.

48. Pneumocystis 1000X, each sperhical cyst 4-7microns

52. The cysts of Pneumocystis carinii in lung have the appearance of crushed ping-pong balls.

53. Toxoplasmosis

54. Toxoplasmosis—DISEASE

58. MAC

59. MAC—MILD LUNG DISEASE

60. MAC—DISEASE

61. MAC—DISEASE

62. OIs for Which Prevention Is Not Routinely Indicated Primary Prophylaxis Bacteria (neutropenia)† Cryptococcosis† Histoplasmosis† Cytomegalovirus† Secondary Prophylaxis Herpes simplex virus § Candida §

63. Primary & Secondary Prophylaxis for Opportunistic Infections When to start? When to stop? When to restart?

64. Indications for Possible Discontinuation of Primary and Secondary Prophylaxis

65. Specific OI’s and specific recommendations OIs for which primary and secondary prophylaxis are recommended OIs for which only primary prevention generally is recommended OIs for which only secondary prevention generally is recommended Infections requiring other management strategies

66. Created 2001, reviewed 6/05 Toxoplasmosis:Secondary Prophylaxis Preferred Regimen: Sulfadiazine 500-1,000 mg QID + pyrimethamine25-50 mg PO QD + leucovorin 10-25 mg PO QD Alternative Regimens: Clindamycin 300-450 mg PO Q 6-8 hours + pyrimethamine 25-50 mg QD + leucovorin 10-25 mg QD Atovaquone 750 mg PO Q 6-12 hours +/- pyrimethamine 25 mg QD + leucovorin 10 mg QD The combination of pyrimethamine plus sulfadiazine plus leucovorin is highly effective for this purpose (AI). A commonly used regimen for patients who cannot tolerate sulfa drugs is pyrimethamine plus clindamycin plus leucovorin (BI). Atovaquone with or without Pyrimethamine plus leucovorin is also used. However, only the combination of pyrimethamine plus sulfadiazine appears to provide protection against PCP as well (AII). The combination of pyrimethamine plus sulfadiazine plus leucovorin is highly effective for this purpose (AI). A commonly used regimen for patients who cannot tolerate sulfa drugs is pyrimethamine plus clindamycin plus leucovorin (BI). Atovaquone with or without Pyrimethamine plus leucovorin is also used. However, only the combination of pyrimethamine plus sulfadiazine appears to provide protection against PCP as well (AII).

67. Created 2001, reviewed 6/05 OIs for Which Only Primary Prevention Generally Is Recommended Tuberculosis section has been updated to reflect 2003 and 2004 CDC recommendations.Tuberculosis section has been updated to reflect 2003 and 2004 CDC recommendations.

68. Created 2001, reviewed 6/05 Tuberculosis:Latent Infection Screening: (5-TU) purified protein derivative (PPD) by the Mantoux method When HIV infection is first recognized Annual test if PPD negative on initial evaluation and continued risk Routine evaluation for anergy is not recommended

69. Created 2001, reviewed 6/05 Tuberculosis:Treatment of Latent Infection Indications: PPD >=5 mm induration at 48-72 hours History of positive PPD with no treatment TB contact (discontinue if PPD negative at 12 weeks All PPD positive patients should be evaluated for active TB, including chest X ray

70. Created 2001, reviewed 6/05 Tuberculosis: Treatment of Latent Infection Recommended Regimen: INH 300 mg PO QD + pyridoxine 50 mg PO QD for 9 months (270 doses)† INH 900 mg PO QD + pyridoxine 100 mg PO twice weekly for 9 months (76 doses )† The generally accepted treatment options for HIV-infected patients regardless of concomitant HAART are isoniazid daily (AII) or twice weekly (BII) for 9 months. For these HIV-infected persons completion of treatment must be assured. Because HIV-infected persons are at risk for peripheral neuropathy, those receiving isoniazid should also receive pyridoxine (BIII). Drug interactions are minimal with the above INH regimens, an advantage over the alternative rifamycin regimens. Directly observed therapy should be used with intermittent dosing regimens (AI) and when otherwise operationally feasible (BIII). HIV-negative individuals can be treated with INH for 6 months, but HIV-infected individuals require a 9 month course. The generally accepted treatment options for HIV-infected patients regardless of concomitant HAART are isoniazid daily (AII) or twice weekly (BII) for 9 months. For these HIV-infected persons completion of treatment must be assured. Because HIV-infected persons are at risk for peripheral neuropathy, those receiving isoniazid should also receive pyridoxine (BIII). Drug interactions are minimal with the above INH regimens, an advantage over the alternative rifamycin regimens. Directly observed therapy should be used with intermittent dosing regimens (AI) and when otherwise operationally feasible (BIII). HIV-negative individuals can be treated with INH for 6 months, but HIV-infected individuals require a 9 month course.

71. Created 2001, reviewed 6/05 Tuberculosis: Treatment of Latent Infection Alternative Regimen: Rifampin 600 mg PO QD for 4 months Note: Rifampin should not be used with protease inhibitors or nevirapine. Rifabutin can be substituted for rifampin for patients taking PI/NNRTIs with appropriate dosage adjustment. Rifampin should not be used with protease inhibitors due to a clinically significant decrease in protease inhibitor serum levels. NNRTIs like efavirenz and nevirapine can be used with rifampin. Efavirenz dose increases to 800mg/d are often recommended in combination with rifampin. A decision to use a regimen containing either rifampin or rifabutin should be made after careful consideration of potential drug interactions, especially those related to protease inhibitors and nonnucleoside reverse transcriptase inhibitors. Dose adjustments for these drugs may have to be made.Rifampin should not be used with protease inhibitors due to a clinically significant decrease in protease inhibitor serum levels. NNRTIs like efavirenz and nevirapine can be used with rifampin. Efavirenz dose increases to 800mg/d are often recommended in combination with rifampin. A decision to use a regimen containing either rifampin or rifabutin should be made after careful consideration of potential drug interactions, especially those related to protease inhibitors and nonnucleoside reverse transcriptase inhibitors. Dose adjustments for these drugs may have to be made.

72. Created 2001, reviewed 6/05 Tuberculosis:Treatment of Latent Infection Rifampin-pyrazinamide (RZ) for 2 months should NOT be given: High rate of severe liver toxicity* *MMWR 2003; 52, 31;735-9  These guidelines are updates from the American Thoracic Society guidelines published in 2000. The significant change to this update is the avoidance of short-course rifampin plus pyrazinamide (RZ) daily for 2 months (DII) or twice weekly for 2-3 months (DIII). Reports of severe liver injury in patients treated with RZ led to this update. These guidelines are updates from the American Thoracic Society guidelines published in 2000. The significant change to this update is the avoidance of short-course rifampin plus pyrazinamide (RZ) daily for 2 months (DII) or twice weekly for 2-3 months (DIII). Reports of severe liver injury in patients treated with RZ led to this update.

73. Created 2001, reviewed 6/05 Tuberculosis: Treatment of Latent Infection When to Restart: Patients previously treated for TB infection or TB disease do not require retreatment based upon diminished immune function alone. Patients with known exposure to TB or suspicion of active TB infection may need treatment. In these instances, consultation with experts is strongly recommended.

74. Created 2001, reviewed 6/05 OIs for Which Only Secondary Prevention Generally Is Recommended

75. Created 2001, reviewed 6/05 Cytomegalovirus Retinitis: Chronic Maintenance Therapy(Following Induction) Consult with a specialist Preferred Regimen:* Valganciclovir 900 mg PO QD Foscarnet 90-120 mg/kg IV QD Ganciclovir implant + PO valganciclovir Alternative Regimens:* Cidofovir IV + probenecid PO Fomivirsen intravitreous injection Prevention of Recurrence CMV disease is not cured with the currently available antiviral agents. Following induction therapy, chronic maintenance therapy is recommended for life (AI), unless there is immune reconstitution as a consequence of effective ARV therapy. Regimens demonstrated to be effective for chronic suppression include parenteral or oral ganciclovir, parenteral foscarnet, combined parenteral ganciclovir and foscarnet, parenteral cidofovir, and (for retinitis only) ganciclovir administration via intraocular implant or repetitive intravitreous injections of fomivirsen (AI). Oral valganciclovir has been approved by the FDA for both acute induction therapy and for maintenance therapy. Repetitive intravitreous injections of ganciclovir, foscarnet, and cidofovir have been reported to be effective for secondary prophylaxis of CMV retinitis in uncontrolled case series. Intraocular therapy alone does not provide protection to the contralateral eye or to other organ systems and typically is combined with oral ganciclovir. 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).Prevention of Recurrence CMV disease is not cured with the currently available antiviral agents. Following induction therapy, chronic maintenance therapy is recommended for life (AI), unless there is immune reconstitution as a consequence of effective ARV therapy. Regimens demonstrated to be effective for chronic suppression include parenteral or oral ganciclovir, parenteral foscarnet, combined parenteral ganciclovir and foscarnet, parenteral cidofovir, and (for retinitis only) ganciclovir administration via intraocular implant or repetitive intravitreous injections of fomivirsen (AI). Oral valganciclovir has been approved by the FDA for both acute induction therapy and for maintenance therapy. Repetitive intravitreous injections of ganciclovir, foscarnet, and cidofovir have been reported to be effective for secondary prophylaxis of CMV retinitis in uncontrolled case series. Intraocular therapy alone does not provide protection to the contralateral eye or to other organ systems and typically is combined with oral ganciclovir. 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).

76. Created 2001, reviewed 6/05 Cytomegalovirus Retinitis:Chronic Maintenance Therapy(Following Induction) When to Consider Discontinuation: Completed initial therapy + no active disease + negative ophthalmologic exam + CD4 >100-150 cells/µL for 6 months on effective ART When to Restart: CD4 <100-150 cells/µL Discontinuation of Chronic Maintenance Therapy should be considered in patients with a sustained, (e.g., 6 months) increase in CD4+ count to >100-150 cells/ L in response to effective ARV therapy (BII). Such decisions should be made in consultation with an ophthalmologist and should take into account such factors as magnitude and duration of CD4+ increase, anatomic location of the retinal lesion, vision in the contralateral eye, and the feasibility of regular ophthalmologic monitoring (BII). All patients who have had anti-CMV maintenance therapy discontinued should have regular ophthalmologic monitoring for early detection of CMV relapse (as well as for immune reconstitution uveitis) (AIII). CMV viral load or other markers of CMV infection, .g., antigenemia, or viral DNA tests are not well standardized; their role in predicting relapse remains to be defined. Relapses have been reported rarely in patients with CD4+ count >100-150 cells/µL. Restarting Secondary Prophylaxis . Relapse of CMV retinitis occurs in patients whose anti-CMV maintenance therapy has been discontinued and whose CD4+ T-lymphocyte count has decreased to 50 cells/ L . Therefore, reinstitution of secondary prophylaxis should be reinstituted when the CD4+ count has decreased to 100-150 cells/ L (AIII). Relapse has been reported in patients whose CD4+ counts are higher then 100 cells/µL, but such reports are rare to date.Discontinuation of Chronic Maintenance Therapy should be considered in patients with a sustained, (e.g., 6 months) increase in CD4+ count to >100-150 cells/ L in response to effective ARV therapy (BII). Such decisions should be made in consultation with an ophthalmologist and should take into account such factors as magnitude and duration of CD4+ increase, anatomic location of the retinal lesion, vision in the contralateral eye, and the feasibility of regular ophthalmologic monitoring (BII). All patients who have had anti-CMV maintenance therapy discontinued should have regular ophthalmologic monitoring for early detection of CMV relapse (as well as for immune reconstitution uveitis) (AIII). CMV viral load or other markers of CMV infection, .g., antigenemia, or viral DNA tests are not well standardized; their role in predicting relapse remains to be defined. Relapses have been reported rarely in patients with CD4+ count >100-150 cells/µL. Restarting Secondary Prophylaxis . Relapse of CMV retinitis occurs in patients whose anti-CMV maintenance therapy has been discontinued and whose CD4+ T-lymphocyte count has decreased to 50 cells/ L . Therefore, reinstitution of secondary prophylaxis should be reinstituted when the CD4+ count has decreased to 100-150 cells/ L (AIII). Relapse has been reported in patients whose CD4+ counts are higher then 100 cells/µL, but such reports are rare to date.

77. Created 2001, reviewed 6/05 Prophylaxis Summary: Fungal Agents The effectiveness of acute treatment for candidiasis along with the low mortality associated with candidal infections, potential for interactions and cost all contribute to the lack of recommendations for routine primary and secondary prophylaxis. As a result, it becomes a patient-specific decision on deciding if secondary prophylaxis is warranted and for how long. It is quite likely that with effective ARV therapy resulting in immune restoration (increased CD4 cell counts) that secondary prophylaxis could be discontinued in patients who chose to start.The effectiveness of acute treatment for candidiasis along with the low mortality associated with candidal infections, potential for interactions and cost all contribute to the lack of recommendations for routine primary and secondary prophylaxis. As a result, it becomes a patient-specific decision on deciding if secondary prophylaxis is warranted and for how long. It is quite likely that with effective ARV therapy resulting in immune restoration (increased CD4 cell counts) that secondary prophylaxis could be discontinued in patients who chose to start.

78. Remember: Each fungal infection requires a specific prophylaxis.

79. Created 2001, reviewed 6/05 Cryptococcosis:Chronic Maintenance Therapy Indication: Upon completion of acute therapy When to Consider Discontinuation: Completed initial treatment + asymptomatic + CD4 >100-200 cells/µL for 6 months on effective ARV therapy When to Restart: CD4 falls to <100-200 cells/µL Prevention of Recurrence Patients who have completed initial therapy for cryptococcosis should be administered lifelong suppressive treatment, (i.e., secondary prophylaxis or chronic maintenance therapy) (AI) unless immune reconstitution occurs as a consequence of effective ARV 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) Adult and adolescent patients appear to be at low risk for recurrence of cryptococcosis when they have successfully completed a course of initial therapy for cryptococcosis, remain asymptomatic with respect to signs and symptoms of cryptococcosis, and have a sustained increase (e.g., 6 months) in their CD4+ T-lymphocyte counts to >100-200 cells/µL following HAART. The numbers of patients who have been evaluated remain small. Based on these observations and on inference from more extensive data suggesting the safety of discontinuation of secondary prophylaxis for other OIs during advanced HIV disease, and while recurrences could occur it may be reasonable to consider discontinuation of chronic maintenance therapy in such patients (CIII). Some experts would perform a lumbar puncture to determine if the CSF is culture negative before stopping therapy even if patients have been asymptomatic; other experts do not believe this is necessary.   Restarting Secondary Prophylaxis Maintenance therapy should be reinitiated if the CD4+ T-lymphocyte count decreases to < 100-200 cells/ L (AIII). Prevention of Recurrence Patients who have completed initial therapy for cryptococcosis should be administered lifelong suppressive treatment, (i.e., secondary prophylaxis or chronic maintenance therapy) (AI) unless immune reconstitution occurs as a consequence of effective ARV 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) Adult and adolescent patients appear to be at low risk for recurrence of cryptococcosis when they have successfully completed a course of initial therapy for cryptococcosis, remain asymptomatic with respect to signs and symptoms of cryptococcosis, and have a sustained increase (e.g., 6 months) in their CD4+ T-lymphocyte counts to >100-200 cells/µL following HAART. The numbers of patients who have been evaluated remain small. Based on these observations and on inference from more extensive data suggesting the safety of discontinuation of secondary prophylaxis for other OIs during advanced HIV disease, and while recurrences could occur it may be reasonable to consider discontinuation of chronic maintenance therapy in such patients (CIII). Some experts would perform a lumbar puncture to determine if the CSF is culture negative before stopping therapy even if patients have been asymptomatic; other experts do not believe this is necessary.   Restarting Secondary Prophylaxis Maintenance therapy should be reinitiated if the CD4+ T-lymphocyte count decreases to < 100-200 cells/ L (AIII).

80. Created 2001, reviewed 6/05 Cryptococcosis: Chronic Maintenance Therapy Preferred Regimen: Fluconazole 200 mg PO QD Alternative Regimen: Itraconazole 200 mg PO QD Prevention of Recurrence Patients who have completed initial therapy for cryptococcosis should be administered lifelong suppressive treatment, (i.e., secondary prophylaxis or chronic maintenance therapy) (AI) unless immune reconstitution occurs as a consequence of effective ARV 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) Adult and adolescent patients appear to be at low risk for recurrence of cryptococcosis when they have successfully completed a course of initial therapy for cryptococcosis, remain asymptomatic with respect to signs and symptoms of cryptococcosis, and have a sustained increase (e.g., 6 months) in their CD4+ T-lymphocyte counts to >100-200 cells/µL following HAART. The numbers of patients who have been evaluated remain small. Based on these observations and on inference from more extensive data suggesting the safety of discontinuation of secondary prophylaxis for other OIs during advanced HIV disease, and while recurrences could occur it may be reasonable to consider discontinuation of chronic maintenance therapy in such patients (CIII). Some experts would perform a lumbar puncture to determine if the CSF is culture negative before stopping therapy even if patients have been asymptomatic; other experts do not believe this is necessary.   Restarting Secondary Prophylaxis Maintenance therapy should be reinitiated if the CD4+ T-lymphocyte count decreases to < 100-200 cells/ L (AIII). Prevention of Recurrence Patients who have completed initial therapy for cryptococcosis should be administered lifelong suppressive treatment, (i.e., secondary prophylaxis or chronic maintenance therapy) (AI) unless immune reconstitution occurs as a consequence of effective ARV 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) Adult and adolescent patients appear to be at low risk for recurrence of cryptococcosis when they have successfully completed a course of initial therapy for cryptococcosis, remain asymptomatic with respect to signs and symptoms of cryptococcosis, and have a sustained increase (e.g., 6 months) in their CD4+ T-lymphocyte counts to >100-200 cells/µL following HAART. The numbers of patients who have been evaluated remain small. Based on these observations and on inference from more extensive data suggesting the safety of discontinuation of secondary prophylaxis for other OIs during advanced HIV disease, and while recurrences could occur it may be reasonable to consider discontinuation of chronic maintenance therapy in such patients (CIII). Some experts would perform a lumbar puncture to determine if the CSF is culture negative before stopping therapy even if patients have been asymptomatic; other experts do not believe this is necessary.   Restarting Secondary Prophylaxis Maintenance therapy should be reinitiated if the CD4+ T-lymphocyte count decreases to < 100-200 cells/ L (AIII).

81. Created 2001, reviewed 6/05 Histoplasmosis: Lifelong Suppressive Therapy Indication: Completion of acute therapy for histoplasmosis When to Consider Discontinuation: Insufficient data (? CD4 >100 cells/µL on ART) Prevention of Recurrence 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).   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 cells/µL, in response to effective ARV therapy, the numbers of patients who have been evaluated are insufficient to warrant a recommendation to discontinue prophylaxis. Prevention of Recurrence 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).   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 cells/µL, in response to effective ARV therapy, the numbers of patients who have been evaluated are insufficient to warrant a recommendation to discontinue prophylaxis.

82. Created 2001, reviewed 6/05 Histoplasmosis: Lifelong Suppressive Therapy Preferred Regimen: Itraconazole 200 mg BID Prevention of Recurrence 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).   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 cells/µL, in response to effective ARV therapy, the numbers of patients who have been evaluated are insufficient to warrant a recommendation to discontinue prophylaxis. Prevention of Recurrence 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).   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 cells/µL, in response to effective ARV therapy, the numbers of patients who have been evaluated are insufficient to warrant a recommendation to discontinue prophylaxis.

83. Created 2001, reviewed 6/05 Salmonella: Prevention of Recurrence Indication: Salmonella septicemia Regimen: Preferred: fluoroquinolones (ciprofloxacin) for susceptible organisms Other Management: Household contacts should be evaluated for carriage so that hygienic measures and/or antimicrobial therapy can be instituted and recurrent transmission can be prevented 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 and/or antimicrobial therapy can be instituted and recurrent transmission to the HIV-infected person can be prevented (CIII).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 and/or antimicrobial therapy can be instituted and recurrent transmission to the HIV-infected person can be prevented (CIII).

84. Created 2001, reviewed 6/05 Infections Requiring Other Management Strategies

85. Created 2001, reviewed 6/05 Human Papillomavirus Infection: Prevention Genital Epithelial Cancers in HIV-Infected Women Pelvic exam + Pap smear twice in first year after HIV diagnosis If normal, repeat Pap smear annually If abnormal, follow consensus guidelines* for management Prevention of Recurrence Careful follow-up and monitoring after treatment No specific therapy recommended HPV-associated Genital Epithelial Cancers in HIV-infected Women After a complete history of previous cervical disease has been obtained, HIV-infected women should have a pelvic examination and a Pap smear. In accordance with the recommendation of the Agency for Health Care Policy and Research, the Pap smear should be obtained twice in the first year after diagnosis of HIV infection and, if the results are normal, annually thereafter (AII). If the results of the Pap smear are abnormal, care should be provided according to the Interim Guidelines for Management of Abnormal Cervical Cytology published by a National Cancer Institute Consensus Panel. No data are available to suggest that these guidelines to prevent cervical disease should be modified for women on ARV therapy. Prevention of Recurrence 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 followup of patients after treatment. Patients should be monitored with frequent cytologic screening and, when indicated, with colposcopic examination for recurrent lesions (AI).HPV-associated Genital Epithelial Cancers in HIV-infected Women After a complete history of previous cervical disease has been obtained, HIV-infected women should have a pelvic examination and a Pap smear. In accordance with the recommendation of the Agency for Health Care Policy and Research, the Pap smear should be obtained twice in the first year after diagnosis of HIV infection and, if the results are normal, annually thereafter (AII). If the results of the Pap smear are abnormal, care should be provided according to the Interim Guidelines for Management of Abnormal Cervical Cytology published by a National Cancer Institute Consensus Panel. No data are available to suggest that these guidelines to prevent cervical disease should be modified for women on ARV therapy. Prevention of Recurrence 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 followup of patients after treatment. Patients should be monitored with frequent cytologic screening and, when indicated, with colposcopic examination for recurrent lesions (AI).

86. Created 2001, reviewed 6/05 HPV-Associated Anal Cancer HIV and HPV coinfected women and men, especially men who have sex with men, are at increased risk for HSIL and anal cancer To date, no formal guidelines recommend anal Pap smear screening, but some specialists recommend this for all HIV-infected adults* Evidence from several studies shows that HPV-positive men who have sex with men and HPV infected women are at increased risk for anal HSILs and might be at increased risk for anal cancer. In view of this evidence, coupled with a recent cost-effectiveness analysis projecting that screening and treatment for anal HSILs provide clinical benefits comparable to other measures to prevent OIs in HIV-infected persons, anal cytology screening of HIV-infected men who have sex with men and women might become a useful preventive measure in the near future. However, further studies of screening and treatment programs for anal HSILs need to be carried out before recommendations for routine anal cytology screening can be made.Evidence from several studies shows that HPV-positive men who have sex with men and HPV infected women are at increased risk for anal HSILs and might be at increased risk for anal cancer. In view of this evidence, coupled with a recent cost-effectiveness analysis projecting that screening and treatment for anal HSILs provide clinical benefits comparable to other measures to prevent OIs in HIV-infected persons, anal cytology screening of HIV-infected men who have sex with men and women might become a useful preventive measure in the near future. However, further studies of screening and treatment programs for anal HSILs need to be carried out before recommendations for routine anal cytology screening can be made.

87. For Additional Information: Sources of Complete Guidelines, Slide Sets and Summaries: AETC Resource Center: www.aids-etc.org AIDSInfo: www.aidsinfo.nih.gov