Diminished immunity despite MMR immunisation in children with perinatally-acquired HIV

Immunity to measles, mumps and rubella in US children with perinatal HIV infection or perinatal HIV exposure without infection.

Siberry GK, Patel K, Bellini W, Karalius B, Purswani M, Burchett SK, Meyer WA, 3rd, Sowers SB, Ellis A, Van Dyke RB, Pediatric HIVACS, Pediatric  HIV AIDS Cohort Study PHACS. Clin Infect Dis. 2015 Jun 9. pii: civ440. [Epub ahead of print]

Background: Children with perinatal HIV infection (PHIV) may not be protected against measles, mumps and rubella because of impaired initial vaccine response or waning immunity. Our objectives were to estimate seroimmunity in PHIV and perinatally HIV-exposed but uninfected (HEU) children and identify predictors of immunity in the PHIV cohort.

Methods: PHIV and HEU were enrolled in the Pediatric HIV/AIDS Cohort Study (PHACS) at ages 7-15 years from 2007-2009. At annual visits, demographic, laboratory, immunization and clinical data were abstracted and serologic specimens were collected. Most recent serologic specimen was used to determine measles seroprotection by plaque-reduction neutralization assay and rubella seroprotection and mumps seropositivity by enzyme immunoassay. Sustained cART was defined as taking cART for at least 3 months.

Results: Among 428 PHIV and 221 HEU PHACS participants, the prevalence was significantly lower in PHIV children for measles seroprotection (57%[95% CI: 52-62%] vs. 99% [95% CI: 96-100%]), rubella seroprotection (65% [95% CI: 60-70%] vs. 98% [95% CI: 95-100%]), and mumps seropositivity (59% [95% CI: 55-64%] vs. 97% [95% CI: 94-99%]). On multivariable analysis, greater number of vaccine doses while receiving sustained cART and higher nadir CD4 percentage between last vaccine dose and serologic testing independently improved the cumulative prediction of measles seroprotection in PHIV. Predictors of rubella seroprotection and mumps seropositivity were similar.

Conclusions: High proportions of PHIV children, but not HEU children, lack serologic evidence of immunity to measles, mumps and rubella, despite documented immunization and current cART. Effective cART before immunization is a strong predictor of current seroimmunity.

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Editor’s notes: Administration of combination measles, mumps and rubella (MMR) vaccine has resulted in dramatic declines in these diseases. Children with HIV, however, may be susceptible to vaccine-preventable diseases despite immunisation, due to weaker or short-lived immunological responses following immunisation. Children living with HIV may be at higher risk of more severe disease. In addition, children who are susceptible to these diseases may contribute to community risk of outbreaks as control of measles, mumps and rubella depends upon a high proportion of the population being immune.

This study demonstrates that sero-protection to rubella and measles and sero-positivity to mumps was substantially lower among children with HIV aged seven to 15 years than among HIV-exposed but HIV-negative children. Notably, nearly all children with HIV in this study had received the full two-dose series of MMR vaccines, in contrast to previous studies where HIV infection has been a risk factor for failure to receive recommended immunisations. Also, despite concerns that HIV-exposed, but HIV-negative children may have subtle immunological abnormalities that could impair their responses to vaccines, the rates of sero-protection and sero-immunity in this group were high, and comparable to rates in the general population.

Previous studies have illustrated that immunosuppression, lack of antiretroviral therapy (ART) or incomplete HIV virologic suppression are associated with a poor response to vaccines. This study demonstrates that a high proportion of older children and youth (all infected perinatally) may not be protected against MMR despite achieving virologic suppression and good immune status with ART.  Timing of receipt of MMR immunisation in relation to ART, but not overall number of vaccine doses, was independently associated with seropositivity to MMR vaccine. Children who received MMR doses after being on sustained ART had significantly higher levels of sero-positivity and sero-protection than children who received MMR vaccine before ART was instituted.    

This study has important policy implications. ART coverage in children globally is still less than coverage in adults. Many children with HIV start ART only in older childhood. Early ART for children followed by the standard MMR schedule as well as repeating MMR vaccine dosing for older children, particularly children who received MMR vaccine prior to starting ART, will be important to avert the risk of these vaccine-preventable infections in this vulnerable population.     

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