HIV-positive children who have experienced immune recovery due to treatment with potent anti-HIV therapy have a good response revaccination with the measles, mumps and rubella (MMR) vaccine, according to a Thai study published in the September 1st edition of Clinical Infectious Diseases.
The investigators also found that revaccination was safe, causing neither significant side-effectors nor a decline in CD4 cell percentage nor an increase in HIV viral load.
In 2006, UNAIDS estimated that there were 2.3 million HIV-positive children around the world. Access to antiretroviral therapy for HIV-positive children is improving, and in Thailand, free anti-HIV treatment has been available for both adults and children since 2002. Thanks to HIV treatment, there has been a significant improvement in the prognosis of HIV-infected Thai children who now have the opportunity to participate in normal childhood activities, such as schooling, and can look forward to surviving into adulthood.
Common childhood illnesses, such as measles, can be more severe in HIV-positive children. Although 98% of Thai children receive measles vaccination, with 88% - 95% developing protective antibodies, the efficacy of such vaccination is much lower in children with weak immune systems. A previous study in Thailand revealed that only 42% of HIV-positive children who received the MMR vaccine developed protective antibodies against measles.
Children who are taking effective anti-HIV therapy have a better response to measles vaccination. But there are outstanding questions about the efficacy of revaccinating such children. Questions also remain unanswered about the optimal timing of revaccination, the efficacy of revaccination, the risk of side-effects, and the possible impact of revaccination on immunological and virological markers.
To answer these questions, investigators at Chiang Mai University Hospital in Thailand designed a prospective study involving 51 antiretroviral-treated HIV-positive children.
All the children were aged over five years, had a nadir CD4 percentage of 15% or below, but had experienced immune reconstitution with an increase in their CD4 cell percentage to above 15% after three months of anti-HIV therapy. None of the children had protective antibodies against measles.
Vaccination with the single-dose MMR vaccine was provided in October 2005.
The children had a mean age of 10 years, 53% were boys, 76% were known to have previously received MMR vaccination, and at the time of vaccination, 55% of children had protective antibodies against rubella and 20% had protective antibodies against mumps. The children had their antibody response to MMR vaccination checked four and 24 weeks after receiving the vaccination.
Approximately half the children (51%) were classified as having AIDS, and the mean nadir CD4 cell percentage was 5%. Anti-HIV therapy was commenced when the children had a mean age of eight years, and the mean duration of HIV therapy at the time of revaccination was 127 weeks. Mean CD4 cell percentage at the time of revaccination was 27% and 92% of children had a viral load below 50 copies/ml.
Four weeks after revaccination with the MMR vaccine, 90% of children had protective levels of antibodies against measles, 78% had protective antibody levels for rubella, and all had protective antibodies against mumps.
After 24 weeks, the percentage of children with protective antibodies against each of the infections covered by the MMR vaccine had declined to 80% for measles, 61% for mumps and 94% for rubella.
No significant adverse events were observed, although 45% of children did report pain at the injection site lasting between one and three days. Nor did revaccination with the MMR vaccine lead to any significant changes in either CD4 cell percentage or HIV viral load.
“The majority of HIV-infected children with immune recovery after HAART developed protective antibodies after MMR revaccination”, comment the investigators.
The investigators note that in a previous US study, only 64% of antiretroviral-treated children who received measles vaccination developed protective antibodies against the infection. But children in that study had been taking HIV therapy for a significantly shorter period (mean, 40 weeks) than the children in the Thai study, and significantly fewer of the US children had an undetectable viral load (64% versus 92%).
Investigators were encouraged by the “excellent” response rate to the rubella component of the vaccination seen in their study. They write, “the excellent response to rubella revaccination that was demonstrated in our study suggests that revaccination of HIV-infected female teenagers who are entering reproductive age decreases the risk of congenital rubella infection in their offspring.”
As regards the proportion of children who developed protective antibodies to mumps after revaccination, the investigators note that this was lower than the proportion of HIV-negative children in other studies. However, three to six months after vaccination, the proportion of healthy children still protected against mumps by vaccination was similar to that seen in the Thai study.
Aurpibul L et al. Response to measles, mumps, and rubella revaccination in HIV-infected children with immune recovery after highly active antiretroviral therapy. Clin Infect Dis 45: 637 – 642, 2007.