Review
Do children infected with HIV receiving HAART need to be revaccinated?

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Summary

No official recommendations have been made on whether children infected with HIV on highly active antiretroviral therapy (HAART) should be revaccinated. We reviewed published work to establish whether these children have protective immunity to vaccine-preventable diseases and to assess short-term and long-term immune responses to vaccination of children given HAART. In general, children on HAART had low levels of immunity to vaccines given before treatment. Most children on HAART, however, responded to revaccination, although immune reconstitution was not sufficient to ensure long-term immunity for some children. These results suggest that children on HAART would benefit from revaccination, but levels of protective immunity might need to be monitored and some children might need additional vaccine doses to maintain protective immunity. Vaccination policies and strategies for children infected with HIV on HAART should be developed in regions of high HIV prevalence to ensure adequate individual and population immunity.

Introduction

As part of the Expanded Programme on Immunization (EPI), WHO recommends giving routine childhood vaccines to children infected with HIV,1 with the exceptions of BCG vaccine to infants with confirmed HIV infection and measles vaccine to severely immunosuppressed children.2, 3 However, because of the progressive effects of HIV infection on the ability of the immune system to mount an effective response, many infected children have poorer responses to vaccines than do uninfected children.4 In general, fewer children infected with HIV achieve protective immunity, and those who do might experience greater and more rapid waning of immunity.4, 5

Highly active antiretroviral therapy (HAART) is effective in reducing morbidity and mortality in children infected with HIV by suppressing viral replication and restoring immune function.6, 7, 8, 9, 10 However, immune reconstitution in children is primarily through the generation of naive T cells rather than expansion of memory T cells, as in adults.11, 12, 13 Consequently, HAART might not restore vaccine-induced immunity established before the start of therapy. No recommendations have been issued on whether children infected with HIV on HAART should be revaccinated.

In low-income and middle-income countries, particularly those in sub-Saharan Africa that bear the greatest burden of HIV infection in children,14 antiretroviral treatment programmes have been scaled-up substantially, increasing access to life-prolonging treatment for children infected with HIV.15 However, these children often access treatment at a later stage in disease progression and at older ages than in more developed countries,16, 17 and will have received routine immunisations before treatment. As a result, revaccination might be important to ensure protection. In countries heavily affected by the HIV epidemic, children receiving HAART who remain susceptible to infection could become sufficiently numerous to sustain transmission of vaccine-preventable diseases and jeopardise control efforts.18

We reviewed published work (table 1)12, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29, 30, 31, 32, 33, 34, 35, 36, 37, 38, 39, 40, 41, 42, 43, 44, 45, 46, 47, 48, 49, 50, 51, 52, 53, 54, 55 to establish whether children taking HAART have protective immunity to vaccine-preventable diseases and to explore short-term (≤3 months) and long-term (>3 months) immune responses to immunisation. The implications of these findings for revaccination of children infected with HIV on HAART are discussed.

Section snippets

Studies of vaccines and HAART

We identified 38 studies that addressed at least one of the questions of interest (table 1). For the question of whether children taking HAART have protective immunity to vaccine-preventable diseases, studies were included if children were vaccinated before being started on HAART and measures of immunity were reported after the start of HAART but before revaccination. Studies of influenza were not included for this question because vaccine-induced immune responses could not be distinguished

Non-replicating vaccines

For non-replicating vaccines, including diphtheria tetanus pertussis vaccine (DTP), hepatitis B vaccine (HBV), pneumococcal vaccines, and conjugate Haemophilus influenzae type b vaccines (Hib), the proportion of children with an immune response, as defined by each study, after being started on HAART was highly variable, with no clear trend by type of vaccine (table 2). The proportion of children with an immune response after being started on HAART ranged from 38% to 77% for tetanus, 40% to 65%

Non-replicating vaccines

Studies of DTP, conjugate Hib, HBV, pneumococcal, and inactivated influenza vaccines involved revaccination of children on HAART who had previously received the same vaccines before starting HAART (table 3). Within the first 3 months after revaccination, the proportion of children responding to vaccination, as defined by each study, was 53–100% for tetanus toxoid,24, 26, 27, 28, 52, 55 75% for conjugate Hib vaccine,55 46–92% for HBV vaccine,35, 37 29–96% by serotype for pneumococcal vaccine,29,

Discussion

The proportion of children with immunity after being started on HAART is low for most vaccines studied, but no characteristic consistently predicted immunity after starting HAART. In general, children infected with HIV on HAART developed immune responses within several months of vaccination, with no differences in the level of primary or secondary responses to new or previously received vaccines. However, immunity waned in some children. In some studies, children on HAART who had a higher

Search strategy and selection criteria

We searched PubMed for articles published in English before April 1, 2010, by use of the terms “HIV”, “antiretroviral therapy”, and “vaccine” (n=835), and also “HIV”, “therapy”, and “vaccine” in combination with “tetanus” (n=60), “pertussis” (n=11), “diphtheria” (n=16), “mumps” (n=21), “hepatitis” (n=229), “influenza” (n=89), “pneumococcal” (n=93), “measles” (n=35), “Haemophilus” (n=19), “varicella” (n=25), and “yellow fever” (n=4). Additionally, we reviewed citations within relevant

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