Long-term immune response to vaccines is impaired in people with HIV

The long-term immune response to most vaccines is impaired in people with HIV, according to the results of a meta-anlaysis published in the online edition of Clinical Infectious Diseases. Comparison with vaccination outcomes in HIV-negative individuals showed that the effect of immunisations waned more rapidly in people with HIV.

“Our analyses showed a rapid decrease in seroprotection after immunization in HIV-infected patients,” comment the authors.

The study has important implications, showing that vaccine responses needed to be closely monitored in people living with HIV and revaccination provided when antibody levels are no longer protective.

It’s already known that initial immune responses to most vaccines are impaired in people with HIV. However, little is known about the persistence of vaccine-induced antibodies in the long-term. This is an important gap in knowledge. Recommendations about booster injections for people with HIV are currently based on data obtained from HIV-negative individuals.

A team of French investigators therefore performed a meta-analysis and systematic review of data from prospective studies reporting on the long-term persistence of antibody concentrations after vaccination with licensed products.

A total of 59 studies were reviewed and 19 were included in the meta-analysis.

Results of the meta-analysis showed that less of half of people with HIV who had a primary response to hepatitis B vaccination still had protective immunity two years after immunisation (28% in adults; 61% in children), and that only 17% were still protected after five years. Doubling the vaccine dose did not improve long-term responses.

A slight decrease over time in the protective immunity provided by hepatitis A vaccination was also observed. Pooled results showed that 92% of individuals were still protected two years after vaccination, and 82% after five years.

Meta-analysis of the measles vaccine was restricted to studies focusing on children who had acquired HIV vertically (through mother-to-baby transmission), immunised between the ages of 6 and 42 months with the MMR vaccine. Pooled results showed that 68% of initial responders still have protective antibodies after two years, falling to 40% after five years.

Protective levels of antibodies to tetanus were present in 74 and 43% of initial responders two and five years after immunisation, respectively. Few studies reported on the long-term responses to vaccination against polio, pertussis and diphtheria. However, all showed that the duration of protection was shorter for children with HIV compared to HIV-negative children.

Analysis of long-term responses to immunisation against Streptococcus pneumoniae included studies examining either the PCV or PPSV23 vaccines. After PPSV23 in adults, rates of decrease in antibody concentrations were either similar or more rapid than those observed in HIV-negative adults. After five years, antibody levels were no longer protective. This was more likely to be the case for people with a low CD4 cell count or detectable viral load at the time of vaccination. Children with HIV who initially responded to Streptococcus pneumoniae immunisation had a significantly greater decline in antibody levels during follow-up compared to HIV-negative children.

Rates of long-term sero-protection among vertically infected children with an initial response to Haemophilus inluenzae b varied between 16% and 78%.

One study looked at responses to the varicella vaccine, showing that less than 50% of children still had detectable antibodies one year after immunisation. Response to yellow fever vaccine was only examined in retrospective studies, their results showing that antibody levels fell more rapidly in people with HIV compared to HIV-negative individuals, with only 17 to 23% still having protective antibody levels ten years post-vaccination. A single study examined the long-term response to vaccination against Japanese encephalitis among children taking HIV therapy. Only a handful of initial responders had lost protective immunity after three years, suggesting the long-term effectiveness of the vaccination in this population.

“Duration of seroprotection…is shorter in HIV-infected patients than in otherwise healthy persons for most licensed vaccines,” comment the authors.

They believe their results have several implications:

• Hepatitis B: Antibodies should be measured yearly in adults and every two to five years in children. Closer monitoring could be considered for people whose initial response to the vaccine is weak.
• Hepatitis A: Individuals with an increased risk of this infection (men who have sex with men, individuals with chronic liver disease, travellers) should have antibody responses checked every five years.
• Tetanus: A booster every ten years should be administered.
• Measles: The initial should ideally be administered after children have started HIV therapy. If viral load is undetectable, two doses are recommended. Children who are vaccinated before they start antiretrovirals, or who have a detectable viral load, should receive a third dose two to five years after initial vaccination.
• Yellow fever: Immunity wanes more rapidly in people with HIV. Antibody levels should be assessed in people at risk of this infection and revaccination is recommended for people who lack protective immunity.
• Streptococcus pneumoniae: Data are too preliminary to inform optimal timing of booster injections for adults.

The investigators were concerned that the median number of participants per study was only 40. They comment: “Data on immunogenicity of vaccines in the immunocompromised host are scarce and the small samples in each category give little power for comparisons between age classes or vaccine schemes.”

The authors suggest that the clinical implications of their findings should be explored in larger prospective studies. They also believe their results have implications for future vaccine research: “The evaluation of new vaccines that specifically target persons with impaired immunity…should confront clinical effectiveness with precise evaluation of both humoral and cellular responses, in an attempt to establish reliable correlates of protection in these populations.”