British HIV Association guidelines for immunization of HIV‐infected adults 2008

Table of contents 1.0 Introduction 1.1 General principles of immunization in HIV-infected adults 1.2 Practical aspects of immunization and general contraindication 2.0 Anthrax 2.1 Background 2.2 Epidemiology and risk groups 2.3 Anthrax vaccine 2.3.1 Vaccine efficacy 2.3.2 Vaccine safety 2.4 Recommendations for anthrax pre-exposure prophylaxis in HIV-infected adults 2.5 Post-exposure prophylaxis 3.0 Cholera 3.1 Background 3.2 Epidemiology and risk groups 3.3 Cholera vaccine 3.3.1 Vaccine efficacy 3.3.2 Vaccine safety 3.3.3 Contraindications 3.4 Recommendations for cholera pre-exposure prophylaxis in HIV-infected adults 4.0 Diphtheria 4.1 Background 4.2 Epidemiology and risk groups 4.3 Diphtheria vaccine 4.3.1 Vaccine efficacy 4.3.2 Vaccine safety 4.4 Recommendations for diphtheria pre-exposure prophylaxis in HIV-infected adults 4.5 Post-exposure prophylaxis 4.6 Auditable outcomes 5.0 Haemophilus influenzae serotype b 5.1 Background 5.2 Epidemiology and risk groups 5.3 Hib vaccine 5.3.1 Vaccine efficacy 5.3.2 Vaccine safety 5.4 Recommendations for H. influenzae pre-exposure prophylaxis in HIV-infected adults 5.5 Post-exposure prophylaxis 5.6 Auditable outcomes 6.0 Hepatitis A 6.1 Background 6.2 Epidemiology and risk groups 6.3 Hepatitis A vaccine 6.3.1 Vaccine efficacy 6.3.2 Vaccine safety 6.4 Human normal immunoglobulin 6.5 Recommendations for hepatitis A pre-exposure prophylaxis in HIV-infected adults 6.6 Post-exposure prophylaxis 6.7 Recommendations for hepatitis A post-exposure prophylaxis in HIV-infected adults 6.8 Auditable outcomes 7.0 Hepatitis B 7.1 Background 7.2 Epidemiology and risk groups 7.3 Hepatitis B vaccine 7.3.1 Vaccine efficacy 7.3.2 Vaccine safety 7.4 Recommendations for hepatitis B pre-exposure prophylaxis in HIV-infected adults 7.5 Post-exposure prophylaxis 7.6 Recommendations for hepatitis B post-exposure prophylaxis in HIV-infected adults 7.7 Auditable outcomes 8.0 Influenza 8.1 Background 8.2 Epidemiology and risk groups 8.3 Influenza vaccine 8.3.1 Vaccine efficacy 8.3.2 Vaccine safety 8.3.3 Contraindication 8.4 Recommendations for influenza pre-exposure prophylaxis in HIV-infected adults 8.5 Antiviral therapy for pre- and post-exposure prophylaxis 8.6 Recommendations for influenza chemoprophylaxis in HIV-infected adults 8.7 Auditable outcomes 9.0 Japanese encephalitis 9.1 Background 9.2 Epidemiology and risk groups 9.3 JEV vaccine 9.3.1 Vaccine efficacy 9.3.2 Vaccine safety 9.3.3 Contraindication 9.4 Recommendations for Japanese encephalitis pre-exposure prophylaxis in HIV-infected adults 9.5 Auditable outcomes 10.0 Measles, mumps and rubella 10.1 Background 10.2 Epidemiology and risk groups 10.3 MMR vaccine 10.3.1 Vaccine efficacy 10.3.2 Vaccine safety 10.3.3 Contraindications 10.4 Human normal immunoglobulin 10.5 Recommendations for measles, mumps and rubella pre-exposure prophylaxis in HIV-infected adults 10.6 Post-exposure prophylaxis 10.7 Recommendations for measles post-exposure prophylaxis in HIV-infected adults 10.8 Auditable outcomes 11.0 Meningococcus 11.1 Background 11.2 Epidemiology and risk groups 11.3 Meningococcus vaccine 11.3.1 Vaccine efficacy 11.3.2 Vaccine safety 11.4 Recommendations for meningococcus pre-exposure prophylaxis in HIV-infected adults 11.5 Post-exposure prophylaxis 11.6 Auditable outcomes 12.0 Pertussis (whooping cough) 12.1 Background 12.2 Epidemiology and risk groups 12.3 Pertussis vaccine 12.3.1 Vaccine efficacy 12.3.2 Vaccine safety 12.4 Recommendations for pre-exposure pertussis prophylaxis in HIV-infected adults 12.5 Post-exposure prophylaxis 12.6 Auditable outcomes 13.0 Pneumococcus 13.1 Background 13.2 Epidemiology and risk groups 13.3 Pneumococcus vaccine 13.3.1 Vaccine efficacy 13.3.2 Vaccine safety 13.3.3 Contraindication 13.4 Recommendations for pneumococcus pre-exposure prophylaxis in HIV-infected adults 13.5 Auditable outcomes 14.0 Poliomyelitis 14.1 Background 14.2 Epidemiology and risk groups 14.3 Polio vaccine 14.3.1 Vaccine efficacy 14.3.2 Vaccine safety 14.3.3 Contraindications 14.4 Recommendations for polio pre-exposure prophylaxis in HIV-infected adults 14.5 Post-exposure prophylaxis 14.6 Recommendations for polio post-exposure prophylaxis in HIV-infected adults 14.7 Auditable outcomes 15.0 Rabies 15.1 Background 15.2 Epidemiology and risk groups 15.2.1 No risk from terrestrial mammals (i.e. excluding bats) 15.2.2 Low risk 15.2.3 High risk 15.3 Rabies vaccine 15.3.1 Vaccine efficacy 15.3.2 Vaccine safety 15.3.3 Contraindications 15.3.4 Pre- and post-vaccination testing 15.4 Rabies immunoglobulin 15.5 Recommendations for rabies pre-exposure prophylaxis in HIV-infected adults 15.6 Recommendations for rabies post-exposure prophylaxis in HIV-infected adults 15.7 Auditable outcomes 16.0 Smallpox 16.1 Background 16.2 Smallpox vaccine 16.2.1 Vaccine efficacy 16.2.2 Vaccine safety 16.2.3 Contraindications 16.3 Recommendations for smallpox prophylaxis in HIV-infected adults 17.0 Tetanus 17.1 Background 17.2 Epidemiology and risk groups 17.3 Tetanus vaccine 17.3.1 Vaccine efficacy 17.3.2 Vaccine safety 17.4 Recommendations for tetanus pre-exposure prophylaxis in HIV-infected adults 17.5 Post-exposure prophylaxis 17.6 Auditable outcomes 18.0 Tick-borne encephalitis 18.1 Background 18.2 Epidemiology and risk groups 18.3 TBE vaccine 18.3.1 Vaccine efficacy 18.3.2 Vaccine safety 18.3.3 Contraindications 18.4 Recommendations for TBE pre-exposure prophylaxis in HIV-infected adults 18.5 Auditable outcomes 19.0 Typhoid fever 19.1 Background 19.2 Epidemiology and risk groups 19.3 Typhoid vaccine 19.3.1 Vaccine efficacy 19.3.2 Vaccine safety 19.3.3 Contraindications 19.4 Recommendations for typhoid pre-exposure prophylaxis in HIV-infected adults 19.5 Auditable outcomes 20.0 Tuberculosis 20.1 Background 20.2 Epidemiology and risk groups 20.3 Bacille Calmette–Guerin vaccine 20.3.1 Vaccine efficacy 20.3.2 Vaccine safety 20.3.3 Contraindications 20.4 Recommendations for TB pre-exposure prophylaxis in HIV-infected adults 20.5 Auditable outcomes 21.0 Varicella zoster virus 21.1 Background 21.2 Epidemiology and risk groups 21.3 VZV vaccine 21.3.1 Vaccine efficacy 21.3.2 Vaccine safety 21.3.3 Contraindication 21.4 Recommendations for varicella pre-exposure prophylaxis in HIV-infected adults 21.5 Post-exposure prophylaxis 21.6 Recommendations for varicella post-exposure prophylaxis in HIV-infected adults 21.7 Auditable outcomes 22.0 Yellow fever 22.1 Background 22.2 Epidemiology and risk groups 22.3 YFV vaccine 22.3.1 Vaccine efficacy 22.3.2 Vaccine safety 22.3.3 Contraindication 22.4 Recommendations for yellow fever pre-exposure prophylaxis in HIV-infected adults 22.5 Auditable outcomes These guidelines provide evidence-graded recommendations on the appropriate use of active and passive immunization in HIV-infected adults. There are several factors that make the formulation of HIV-specific immunization guidelines important at a time when highly active antiretroviral therapy (HAART) is modifying the natural history of HIV infection, vaccination practices are changing and new vaccines are becoming available in clinical care. Compared with healthy individuals, HIV-infected adults may have an increased risk of infection or experience more severe disease following exposure to vaccine-preventable diseases. As a result, a lower threshold for recommending immunization may be indicated relative to the general population. Responses to vaccination are often sub-optimal in HIV-infected persons, who may benefit from higher or more frequent vaccine doses. Furthermore, reduced rates and durability of responses may require more frequent use of serological testing than is generally recommended, in order to determine antibody levels after vaccination and guide boosting requirements. As a result of improved health and prognosis, HIV-infected persons are increasingly likely to engage in exposure-prone activities related to occupation or travel, and may require vaccines that are traditionally contraindicated in immunocompromised persons but may be safe to use in HIV-infected persons with restored immunity. Safety of vaccination remains an important consideration. Inactivated vaccines can be used safely in HIV-infected persons if indicated (Table 1). In some cases, the increased risk of adverse reactions either contraindicates the use of certain vaccines or restricts them to HIV-infected persons with good immune function. Traditionally, live vaccines have been contraindicated in HIV infection. However, HAART-induced immunoreconstitution is either known or expected to reduce the risk of adverse events, in many cases shifting the risk–benefit ratio in favour of vaccination. Important examples of live vaccines that can be used cautiously in HIV-infected persons include those for measles, mumps and rubella (MMR), varicella and yellow fever (Table 2). Other live vaccines remain contraindicated, either because safer inactivated alternatives are available (e.g. typhoid) or because of a lack of safety data and uncertainty about vaccine efficacy [e.g. Bacille Calmette–Guerin (BCG)] (Table 3). Tables 4–6 summarize the recommendations for pre-exposure prophylaxis. Table 7 summarizes the recommendations for travel-related vaccination. Table 8 summarizes the recommendations for post-exposure prophylaxis. The reader should refer to the specific sections for further details. Because there is a paucity of controlled studies to inform the formulation of HIV-specific immunization guidelines, the recommendations given here are often the expression of a consensus derived from descriptive studies, clinical experience and expert opinion (Table 9). They are therefore likely to evolve as new data emerge. Available evidence was obtained from published peer-reviewed studies and from studies presented at international conferences in the last 5 years. In addition, the following websites were consulted: the Health Protection Agency (HPA; http://www.hpa.org.uk); the USA Centers for Disease Control and Prevention (CDC; http://www.cdc.gov); and the World Health Organization (WHO; http://www.who.int/en). The guidelines are generally consistent with and expand the recommendations issued in The Green Book, published by the Department of Health, the Scottish Executive, the Welsh Assembly Government and the Department of Health, Social Services and Public Safety, which should be seen as complementary guidance [1]. It is recognized that the responsibility for providing the recommended immunizations and for meeting the associated costs remains an unresolved issue. It is currently envisaged that the HIV specialist should provide overall guidance on vaccine use and enlist the help of primary care physicians for vaccine administration where feasible. As is the case with HIV-negative travellers, HIV-infected persons should be advised that they will be expected to meet the cost of vaccines required for travel. Finally, while it is hoped that these guidelines will inform immunization practices widely, they are intended primarily for HIV-infected adults in the UK. Persons with symptomatic HIV infection or CD4 counts <200 cells/μL must not be given live vaccines. If indicated, vaccination should be reconsidered following immunoreconstitution. Household and other close contacts of severely immunocompromised HIV-infected persons should not receive the oral polio and the intranasal influenza vaccines, but can receive the MMR, varicella and yellow fever vaccines. Asymptomatic HIV-infected persons with CD4 counts >400 to 500 cells/μL are generally regarded as sufficiently immunocompetent, whereas those with CD4 counts between 200 and 400–500 cells/μL are considered to have limited immunodeficiency. While acknowledging that treated persons with previous symptomatic disease and low nadir CD4 cell counts may have incomplete immunoreconstitution, it is generally recommended that the current CD4 cell count can be used to categorize HIV-infected persons. When safety concerns restrict vaccine use according to the level of immunoreconstitution, it is recommended that the CD4 cell count has been stably above the threshold for at least 3 months before proceeding with vaccination. In all cases, the immunocompetence of individual patients should be judged clinically. Regardless of the CD4 cell count, the contraindications to the use of live vaccines that apply to the general population also apply to HIV-infected persons. For further details the reader should refer to The Green Book [1]. Risk groups include patients in the following categories: Currently being treated for malignant disease with immunosuppressive chemotherapy or radiotherapy, or have terminated such treatment within the previous 6 months; Have received a solid organ transplant and are currently on immunosuppressive treatment; Have received a stem-cell transplant, until at least 12 months after finishing all immunosuppressive treatment (or longer where the patient has developed graft-vs.-host disease); Receiving systemic steroids until at least 3 months after treatment has stopped (in the general population, the threshold is at least 40 mg of prednisolone per day for more than 1 week; lower doses may be associated with significant immunosuppression in HIV-infected persons); Receiving other types of immunosuppressive drugs (e.g. azathioprine, cyclosporin, methotrexate, cyclophosphamide, leflunomide or the newer cytokine inhibitors) alone or in combination with lower doses of steroids, until at least 6 months after terminating such treatment. In vaccine candidates with CD4 counts <200 cells/μL, consideration may be given to delaying immunization until the CD4 cell count has recovered with HAART. Because responses to vaccination can be observed in a substantial proportion of patients with CD4 counts <200 cells/μL, the potential benefit of immunization should not be denied to such persons. Therefore, it is generally recommended that vaccination should be given to persons with CD4 counts <200 cells/μL if indicated and safe, and repeated following immunoreconstitution if required. Considerations on destination and risk behaviour apply equally to HIV-positive and HIV-negative travellers. However, the consequences of not administering an indicated vaccine may be more severe in HIV-infected persons. Modification of the travel itinerary may be required where a vaccine is contraindicated in an HIV-infected person, if the risk of infection is significant. HIV-infected vaccine recipients should be advised that the levels and duration of protection induced by vaccination may be reduced relative to healthy individuals. The importance of additional measures of protection (e.g. against insect bites) should be emphasized. Transient increases in plasma HIV RNA load have been reported after the administration of several vaccines. Available evidence indicates that the transient increases do not have clinical significance [2,3]. These effects will not be discussed further because they should not preclude the use of any vaccine. For these, the reader should refer to The Green Book [1]. In general: Live vaccines can be administered simultaneously in different sites or with an interval of 4 weeks. When multiple vaccines are given at the same time a separate site should be used. If the vaccines are given in the same limb, they should be given at least 2.5 cm apart. Live vaccines should be administered at least 14 days before or 3 months after the administration of antibody-containing blood products, because passively acquired antibodies may interfere with the response to the vaccine. As a general rule, vaccines are contraindicated in persons with a history of previous severe adverse reaction or allergy to the vaccine or its components. In addition, persons with acute moderate or severe febrile illness usually should not be vaccinated until their symptoms have abated. Inactivated vaccines may be used in pregnancy if there is a significant risk of infection. Live vaccines are instead contraindicated in pregnancy, although in most cases the theoretical risk to the developing foetus is expected to be low. The reader should seek specialist advice about vaccination in pregnancy [1]. Bacillus anthracis is a toxin-producing gram-positive bacterium transmitted through spores that can be found in animal products and can remain viable in the environment for years. The infection occurs primarily in herbivorous mammals. Human infection is rare and occurs almost exclusively after contact with infected animals or animal products. Person-to-person transmission may occur through contact with skin lesions but is unusual. The incubation period of anthrax is usually 1–7 days, but can range up to 8 weeks. The disease may present as one of three main syndromes: cutaneous, following direct contact with spores, spore-contaminated material or infected skin lesions (>95% of cases, rare mortality); respiratory, following inhalation of spores (50% mortality); and gastrointestinal, following ingestion of contaminated meat (very rare, 25–60% mortality). Meningitis may occur and is usually fatal. Provided it is recognized early, anthrax can be treated effectively with antibiotics. Post-exposure prophylaxis can also prevent disease if given early enough. Anthrax occurs in Asia, Africa and parts of Europe and the Americas. In the UK, human anthrax is rare and is seen almost entirely as an occupational disease in persons handling imported animal products or working with infected animals. Cases have been reported in abattoir workers, tannery/leather workers, farm workers, butchers, engineers, textile workers and bone meal workers. It is not known whether the natural history of anthrax is modified by HIV infection. The anthrax vaccine is inactivated. It contains alum-precipitated antigen derived from the Sterne strain of B. anthracis. In the UK, the only licensed vaccine is manufactured by the HPA and supplied to the Department of Health for occupational health purposes and to the Ministry of Defence to protect service personnel from the use of anthrax as a biological weapon [1]. The vaccine is given by intramuscular injection (or subcutaneously in persons with bleeding disorders), preferably in the deltoid. There have been no formal efficacy trials with the UK vaccine and no data are available on vaccine efficacy in HIV-infected persons. The vaccine is safe [4]. It may cause mild injection site reactions and (more rarely) lymphadenopathy, fever, flu-like symptoms, rash, itching or other allergic reactions. The anthrax vaccine is indicated in those with a significant risk of exposure [C, IV (see Table 9 for definitions of evidence levels)]. The primary course consists of four doses. The second dose is given at least 3 weeks after the first, the third dose at least 3 weeks after the second, and the fourth dose at least 6 months after the third (C, IV). A single booster dose is given once a year (C, IV). Following credible or confirmed exposure to anthrax, the person at risk should receive post-exposure prophylaxis with oral ciprofloxacin, doxycycline or amoxicillin (if the strain is susceptible) for 60 days and may also be given the vaccine. Immunization is recommended because of the uncertainty of when or if the inhaled spores may germinate. Advice must be obtained from the Immunization Department of the HPA Centre for Infections (tel: + 44 20 8200 6868). Vibrio cholerae is a non-invasive toxin-secreting gram-negative bacterium that colonizes the small bowel. Classification into over 100 serogroups is based on the polysaccharides of the somatic (O) antigen. Cholera epidemics are caused by the O1 serogroup, and more recently by the O139 serogroup in south and south-east Asia [5]. The infection is acquired through the faecal–oral route, primarily by consuming contaminated water or food; person-to-person transmission is rare. Mankind is the only known host. The incubation period of cholera ranges from <1 day to 5 days. The disease is characterized by sudden onset of painless, profuse watery diarrhoea and responds to fluid- and electrolyte-replacement therapy. In extreme cases, hypotension and death can occur within 6–8 h of the onset of symptoms. Approximately 80% of infected people have mild diarrhoea or may be asymptomatic. Seven cholera pandemics have been recorded throughout history. The latest started in 1961 and it is still ongoing in regions of Asia, the Middle East, Africa, and central and Latin America, with 3–8 million cases reported each year. Large outbreaks are usually caused by a contaminated water supply. In developed countries, cases are reported sporadically in travellers, with an overall risk of two to three cases per million travellers. Cholera is rare among UK travellers, and is seen predominantly among those who visit the Indian sub-continent. Travellers who follow the usual tourist itineraries, use standard tourist accommodation and observe food safety recommendations while in countries reporting cholera have little risk. The risk increases for long-term travellers and for those who drink untreated water, eat poorly cooked or raw seafood, or live in unsanitary conditions in disease-endemic areas (e.g. aid workers assisting in disaster relief or refugee camps and adventurous backpackers travelling to remote areas) [6]. Currently, no country requires proof of vaccination against cholera as a condition for entry. However, local authorities may require of vaccination. Persons with disease or may be at increased risk for severe also that in HIV infection is associated with an increased risk for cholera oral cholera vaccines are available The vaccine available in the UK contains inactivated and of cholerae serotype with of the cholera in of cholerae serotype O1 [1]. The cholera vaccine based on inactivated cholerae O1 is still in some countries but it is not generally recommended because it and of the live vaccine has currently been In healthy persons, the oral cholera vaccines days after the second dose and for at least 1 year The level of protection is after 3 years. there is protection of have received the vaccine The vaccine is not expected to protection against cholerae not to provide some protection against diarrhoea caused by toxin-producing the 3 months following vaccination However, use for the specific of diarrhoea remains There have been no published of the efficacy of the vaccine in HIV-infected individuals. A in in a population persons HIV-infected adults with CD4 counts cells/μL may be expected to poorly to oral cholera vaccines, whereas those with CD4 counts cells/μL improved responses after two doses of is in HIV-infected persons. The vaccine may cause symptoms. of and have been reported in rare and are rare. The vaccine is in HIV-infected The vaccine should not be with other oral vaccines. should be considered for HIV-infected persons if they are to travel to highly areas and in one of the risk groups (C, IV). The vaccine is not indicated for most travellers, but should be considered for those who are to in highly or or may be at risk of severe disease if HIV-infected persons should receive two doses of the oral vaccine given at least 1 apart. If more than 6 weeks have the the course should be A single booster dose should be given after if protection is required. If more than have of the primary vaccine the primary course should be repeated (C, IV). The importance of food and water should be emphasized. The live vaccine is contraindicated because of safety Diphtheria is caused by of the gram-positive or The infection is transmitted generally as a result of close contact with patients or with untreated disease may be for up to 4 weeks. may be and the infection for The normal of is rare human cases have been associated with the of raw products. The incubation period of diphtheria is days. The disease the and the include and In countries with vaccine the the of has and there is little risk of exposure of of in of the and diphtheria cases to be reported from the Indian south-east Asia, America, Africa and recently the The potential for infection and into the UK through travel to and from these regions remains a to diphtheria increases with and it is that of UK adults over of are to countries and close contact with or other farm animals are potential risk factors for infection. It is not known whether the natural history of diphtheria is modified by HIV infection. The diphtheria vaccine is from from treated with into diphtheria and or The vaccine is given to adults in combination with tetanus and inactivated polio vaccines in a a lower of diphtheria than for use in [1]. The vaccine is administered by intramuscular injection (or injection in persons with bleeding disorders), preferably in the deltoid. In healthy persons the diphtheria vaccine levels in of after three doses and a clinical efficacy of over responses are seen following a booster dose in adults data on the and clinical efficacy of the vaccine in HIV-infected adults. Vaccine responses may be reduced to HIV-negative persons in those with disease and low CD4 cell counts but may with highly active antiretroviral therapy (HAART) The diphtheria vaccine is safe in HIV-infected persons site reactions are but usually and may occur more following doses. and other systemic reactions are reactions such as or have been reported is recommended in all HIV-infected persons of CD4 cell counts and should be given in with standard A vaccine course consists of doses. who have not been or have vaccination should receive three doses at least 1 apart. further boosting doses should be given after 5 and years. who have received three doses as and one booster at of four require a single booster Persons who have received doses require a booster dose at if at risk of exposure (C, IV). There is no to a if more than the recommended time between doses has who may be to diphtheria in the course of their (e.g. should be for antibodies 3 months after vaccination to immunity. who are close contacts of a case of diphtheria should receive vaccination and prophylaxis as as should receive three doses of should receive a single booster dose of a booster dose was given within the year. The recommended for prophylaxis for adults is a single dose of intramuscular or 500 mg 6 h for 7 days. of primary vaccination Haemophilus influenzae is a gram-negative transmitted through contact with infection is usually caused by