An immunisation (often called a vaccination) is designed to protect the recipient against an infectious disease. Different vaccines are produced in different ways, but all work in a similar way.

For hundreds of years it has been recognised that people who have recovered from an illness tend not to be vulnerable to it again: in other words, they have become immune to it. This is because after the immune system is exposed to an antigen, some immune cells become 'memory cells'. When the individual next encounters the same antigen, these memory cells mean that the immune system is already primed to deal rapidly with the antigen before it can establish a lasting infection.

Vaccines take advantage of this mechanism by priming the immune system using forms of the organism which cannot cause disease, thus stimulating immunity against the 'real' pathogenic (disease-causing) organisms found naturally.

There are three main types of vaccine. Live attenuated vaccines contain the whole actual organism that causes disease, but in a weakened form so that it is unable to cause disease. Inactivated vaccines contain dead organisms which cannot therefore cause infection, but which the immune system can still recognise. Sub-unit vaccines contain only a fragment or part of the organism which is unable to cause infection but which is still sufficient to prime the immune system against the whole organism.

Some sub-unit vaccines prime the immune system against harmful substances produced by micro-organisms. For example, the tetanus toxoid vaccine is an immunisation against the poison which the tetanus organism produces, rather than against the tetanus organism itself.

The most effective form of vaccine is usually the live attenuated vaccine, because it comes closest to the real conditions in which the immune system is exposed to an antigen and develops memory responses against it.

There are particular issues to consider concerning immunisations for people with HIV. Although killed vaccines and sub-unit vaccines are perfectly safe for HIV-positive people because they contain no infectious matter, there is a danger that a damaged immune system may not be able to control even the weakened or low doses of organisms found in live attenuated vaccines. In other words, there is a theoretical risk with live attenuated immunisations that the vaccine might actually cause the illness it is intended to protect against. However, as more evidence has come to light over the years it has become clear that in many cases live vaccines are safe for people with HIV.

Recommendations for people with HIV

The current advice on immunisations for HIV-positive people is contained in the memorandum Immunisation against Infectious Disease, produced by the Joint Committee on Vaccination and Immunisation (JCVI) of the Department of Health.

The standard guidelines for each vaccine should be used to determine whether a person with HIV should be immunised. For example, hepatitis B vaccine is recommended for injecting drug users, people who change sexual partners frequently, people with haemophilia, health care workers and other occupational risk groups. It may be wise for all HIV-positive people to receive hepatitis B immunisation since they are at increased risk of becoming chronic hepatitis B carriers if they become newly infected. Other vaccines are usually only given to people who are travelling to countries where the disease in question is relatively common.

Current advice is that the following live vaccines are safe for all but severely immune suppressed individuals with HIV:

• Measles.

• Mumps.

• Rubella.

• Polio, although the killed polio vaccine is preferred in people with immune deficiency.

HIV-positive people should not receive the Bacille Calmette-Guerin (BCG) vaccine for tuberculosis.

There is no risk with killed vaccines, and people with HIV are advised to receive the following as circumstances require:

• Whooping cough.

• Diphtheria.

• Tetanus.

• Polio.

• Haemophilus influenzae type B (Hib).

• Typhoid, although immuno-suppressed people should not receive the oral live typhoid vaccine.

• Cholera.

• Hepatitis A.

• Hepatitis B.

• Influenza.

• Meningococcus.

The pneumococcal vaccine is also recommended but it is unclear whether pneumococcal it is protective in HIV-positive people, despite United Kingdom guidelines recommending that immunisation should be considered in those for whom pneumococcal infection is likely to be most dangerous. Approval of the vaccine was based on several studies which showed that pneumococcal immunisation stimulates the immune system, leading to a temporary increase in viral load, rather than reducing disease.

Recently, a large, placebo-controlled study found that the vaccine had no impact on rates of pneumoccocal disease among people with HIV in Uganda, and there was an increased risk of all forms of pneumonia in vaccine recipients (French 2000). This raises doubts about the efficacy of the vaccine in people with HIV and suggests that the vaccine is in fact causing harm. Previously, studies suggested low rates of antibody response to the vaccine in HIV-positive people when compared to uninfected people although one study found that many HIV-infected children had a satisfactory response to revaccination (Viani 2000).

Hepatitis A vaccination has been shown to be more successful in individuals with higher CD4 cell counts. Whilst over 60% of HIV-positive people with CD4 cell counts above 500 cells/mm³ developed antibodies within six months, only 13% of people with CD4 cell counts below 200 cells/mm³ had developed antibodies (Kemper 2003). In a similar study, 100% of 45 patients with CD4 cell counts of 300 cells/mm³ or above developed hepatitis A antibodies, in contrast to 87% of 45 with CD4 cell counts below this value (Wallace 2004).

Live vaccines

Several of the live vaccines raise particular issues for people with HIV.

Measles can be a very serious illness in people with HIV. There is a slight risk that the live measles vaccine may cause illness in people with HIV, especially among those with advanced disease. United States authorities now recommend withholding measles vaccination from adults with CD4 cell counts below 200 cells/mm³, children aged 1 to 5 with CD4 counts below 500 cells/mm³, and children aged under 12 months with CD4 counts below 750 cells/mm³. Vaccination is not normally considered necessary in the United Kingdom where the disease is relatively rare, but in areas such as west Africa where measles is endemic, the small risk from the vaccine has been shown to be outweighed by the protection it can provide against catching measles.

In the United Kingdom most people receive the live polio vaccine on a sugar cube when they are children. After receiving this vaccine it is usual for people to excrete the polio virus itself in their faeces for several weeks after immunisation. This is potentially infectious to people who have not been immunised, especially if they are also HIV-positive. For this reason, it may be sensible for babies to be given the killed polio vaccine (which has to be specially ordered) if a carer is HIV-positive. If this is impossible, gloves should be worn when changing the nappies of recently immunised babies.

If people with HIV are travelling to an area where polio is endemic, it is wise to be vaccinated. Those who received the sugar-cube vaccine when children (probably the majority) are advised to have a booster with the live vaccine. There has been one case report of polio in a child with HIV following administration of the live polio vaccine .

A killed polio vaccine is also available. It is equally effective but has to be given by injection. Since there is a choice of polio vaccine, many doctors consider it prudent to use the killed vaccine in HIV-positive people, especially those who did not receive the vaccine when children or those who have developed symptoms.

Yellow fever is another live vaccine. The Department of Health recommends that it should not be given to asymptomatic or symptomatic people with HIV because not enough is yet known as to its safety. However, clinicians report that yellow fever vaccine has been given without problems to many asymptomatic people, and a recent small retrospective study has shown that it is safe and effective in HIV-positive people with CD4 cell counts above 200 cells/mm³. All twelve recipients developed yellow fever antibodies, without affecting CD4 cell counts or viral loads after three months (Tattevin 2004).

People with HIV who are travelling to countries where yellow fever is endemic may be required to produce a certificate of vaccination. If vaccination is inadvisable for medical reasons such as HIV infection your doctor should be able to provide you with a letter of exemption.

Although there has been conflicting evidence about the benefits of the influenza vaccine in people with HIV, more recent studies have found it safe and effective in people on highly active antiretroviral therapy (HAART) with CD4 counts above 150 cells/mm³. One placebo-controlled study of 47 people found that the vaccine may not be warranted, since those who had the vaccine experienced a significant drop in their CD4 percentage at three months. However, a randomised, double-blind, placebo-controlled study of 102 HIV-infected individuals found that the influenza vaccine was highly effective and that it was not associated with significant changes in viral load or CD4 cell counts (Tasker 1999). Another study of the flu vaccine found 20% of 89 HIV-infected patients and 25% of 12 controls developed influenza within 12 weeks. The ability of the vaccine to trigger an immune response was crucial in preventing illness: a majority of individuals who did not experience a four-fold increase in antibodies developed influenza. CD4 cell count fell by more than 75 cells/mm³ in 15 HIV-infected patients and rose by more than 0.5 log₁₀ in 14 (Frederick 2000).

However, the largest influenza vaccine study to date prospectively evaluated the efficacy of and immunologic responses to the vaccine in 328 HIV-positive patients. In total, 10% of the vaccinated patients 26% of the non-vaccinated participants were diagnosed with influenza during the winter of 2002. However, there was no significant difference seen between the vaccinated and non-vaccinated groups in those patients with CD4 counts below 150 cells/mm³. Antibody responses were similar in those both taking and not taking HAART, but specific CD4 responses were seen to be better in those on HAART, suggesting that HAART may improve the efficacy of the influenza vaccine (Yamanaka 2004).

United States guidelines

The United States Public Health Department and the Infectious Diseases Society of America has issued joint guidelines on the prevention of opportunistic infections among people with HIV. Vaccination recommendations include:

• Pneumococcal vaccine for all HIV-infected individuals with a CD4 count above 200 cells/mm³ who have not been vaccinated in the previous five years. Vaccination may be offered to HIV-infected individuals with a CD4 count below 200 cells/mm³ despite diminuished effectiveness, with a repeat vaccination if CD4 count rises above 200 cells/mm³.

• Annual influenza vaccination.

• Hepatitis B vaccination if seronegative.

• Hepatitis A vaccination if seronegative for hepatitis C virus.

Vaccinations for children

There are special considerations for children, particularly in developing countries. In order to prevent childhood infections it is important for children to receive all their routine childhood immunisations. Generally immunisations are effective in children who do not have any symptoms, but they are less effective if the child is symptomatic or has AIDS. All immunisations should be given at the normal time for diphtheria, tetanus, pertussis, polio, mumps and rubella.

Following the death of a young man from measles following a vaccination, the American Academy of Pediatrics reviewed its recommendations. In May 1999, the academy endorsed current practice: that vaccinations for measles, mumps and rubella should be given to all HIV-infected children and young adults, unless they have very low CD4 counts (Halsey 1999).

One exception to the rule is the BCG vaccine against tuberculosis. It is not advised for children known to be HIV-positive, especially if they have symptoms. Hepatitis B vaccine should be given to babies whose mother is a hepatitis B carrier. Varicella zoster virus or measles immunoglobulin should be given to an HIV-infected child who is in contact with chickenpox or measles as this will help to prevent the illness or make it less severe. It is important to tell the doctor if an HIV-infected child has been exposed to these illnesses.

The World Health Organization has recommended that HIV-infected children receive a double dose of the rabies vaccination if they have been exposed to rabies. HIV-infected children have a much weaker immune response to the standard vaccination compared with uninfected children (Thisyakorn 2000).

H. influenzae type B and pneumococcal vaccine are recommended for children with HIV infection. During an influenza epidemic, HIV-positive children should be offered vaccination.

Vaccination and viral load testing

Immunisations and other factors that activate the immune system may boost HIV replication leading to an increase in viral load. Experiments using tetanus booster immunisations found that people with HIV experienced two- to 36-fold increases in viral load following the injection, but that viral levels returned to baseline within six weeks (Stanley 1996).

Increases in viral load have also been seen among people given influenza immunisations. Researchers consider it unlikely that this short-term increase will have any impact on the health of immunised people, although strictly speaking this remains unproven. Nevertheless, there is near universal agreement that if a person would normally be advised to receive an immunisation, the benefits of being protected against the micro-organism in question outweigh the theoretical dangers of the short-term rise in HIV viral load.

A very large review of HIV-positive patients in the United States found no difference in the rate of CD4 cell decline between those who received the influenza vaccine and those who did not. Medical records from 36,100 patients were analysed to review disease progression trends between 1990 and 1999. Vaccination was associated with a slightly lower risk of developing an AIDS-defining illness, but did not significantly improve the survival of people with HIV (Sullivan 2000).

Viral load testing is not recommended for at least four to six weeks after a vaccination, since during the temporary period of increased HIV replication the test may give an artificially high estimate of viral load. In particular, decisions about starting or changing treatment should be postponed until the temporary burst of viral activity stimulated by vaccination has had time to die down.

References

CDC. Measles pneumonitis following measles-mumps-rubella vaccination of a patients with HIV infection, 1993. Morbidity and Mortality Weekly Report 45(28), 19^th July 1996.

Chitsike I et al. Paralytic poliomyelitis associated with live oral poliomyelitis vaccine in child with HIV infection in Zimbabwe: case report. British Medical Journal 318(7187): 841-843, 1999.

Frederick S et al. Evaluation of HIV infected patients post influenza vaccination. Thirteenth International AIDS Conference, Durban, abstract B2163, 2000.

French N et al. 23-valent pneumococcal polysaccharide vaccine in HIV-1-infected Ugandan adults: double-blind, randomised and placebo controlled trial. Lancet 355(9221): 2106-2111, 2000.

Halsey NA et al. Measles immunization in HIV-infected children. Pediatric 103(5): 1057-1060, 1999.

Kemper CA et al. Safety and immunogenicity of hepatitis A vaccine in HIV-infected patients: A double-blind, randomized, placebo-controlled trial. Journal of Infectious Diseases, 187, on-line edition, 2003.

Stanley SK et al. Effect of immunization with a common recall antigen on viral expression in patients infected with human immunodeficiency virus type 1. New England Journal of Medicine 3334(19): 1222-1230, 1996.

Sullivan PS et al. Effect of influenza vaccination on disease progression among HIV-infected persons. AIDS 14: 2781-2785, 2000.

Tasker SA et al. Effects of influenza vaccination in HIV-infected adults: a double-blind, placebo-controlled trial. Vaccine 16(9-10): 1039-1042, 1998.

Tasker SA et al. Efficacy of influenza vaccination in HIV-infected persons. Annals of Internal Medicine 131: 430-433, 1999.

Tattevin P et al. Yellow fever vaccine is safe and effective in HIV infected patients. AIDS 18: 825-827, 2004.

Thisyakorn U et al. Safety and immunogenicity of preexposure rabies vaccination in children infected with human immunodeficiency virus type 1. Clinical Infectious Diseases 30(1): 218, 2000.

Viani R et al. Antibody to pneumococcal polysaccharide vaccine in children with HIV infection: effect of revaccination. Thirteenth International AIDS Conference, Durban, abstract B5135, 2000.

Wallace MR et al. Safety and immunogenicity of an inactivated hepatitis A vaccine among HIV-infected subjects. Clin Infect Dis 39: 1207-1213, 2004.

Yamanaka H et al. Efficacy of and Immunologic Responses to Influenza Vaccine in HIV-1-infected Patients: A Prospective Study Eleventh Conference on Retroviruses and Opportunistic Infections, San Francisco, abstract 231, 2004.