Booster dose of measles vaccine achieves high levels of protection for children taking effective HIV treatment

A booster dose of the measles vaccine produces protective antibody responses and immunologic memory in children receiving HIV therapy, US investigators report in the online edition of the Journal of Infectious Diseases.  A viral load below 400 copies/ml was associated with vaccine response.

“The present study reinforces the safety and potential value of measles (re)vaccination, when administered with an adequate CD4 cell % in the context of HAART [highly active antiretroviral therapy], to achieve high response rates with persisting immunologic memory,” write the investigators.

Measles can cause severe disease in HIV-positive children. The infection is endemic in the world regions that have the highest prevalence of HIV, and measles is therefore the cause of significant levels of serious illness and death in HIV-positive children in resource-poor countries.

A measles vaccine has been available since the 1960s. However, response rates to this live vaccine are reduced in immune-suppressed people. There are also concerns about its safety when administered to children with a low CD4 cell count.

Little is known about the immunity that a booster dose of the vaccine provides to children taking antiretroviral therapy.

Investigators from the International Maternal Adolescent AIDS Clinical Trials Group (IMPAACT) therefore designed a study to assess the protective effect of measles revaccination. Their study sample involved 193 children aged between 2 and 19 years. All were on stable antiretroviral therapy and had a CD4 cell percentage above 15% and a viral load below 30,000 copies. The children had previously received one or more dose of the combined measles, mumps and rubella (MMR) vaccine. Measles antibody concentrations were monitored before revaccination and then 8, 32 and 80 weeks after receiving the booster. A sub-set of 65 children was given another dose of the MMR vaccine approximately four years later. Measles antibody levels were measured before, and then 7 and 28 days later. The investigators conducted a series of analyses to see which factors were associated with a response to revaccination and the persistence of antibody memory.

On entry to the study, 83% of children had detectable measles antibodies. In 52%, antibody levels were sufficient to provide protection against the infection (plaque reduction neutralisation of or above 120 miu/ml). Eight weeks after receiving the booster, the proportion of patients with protective levels of antibodies had increased to 89%.

After controlling for potential confounders, the investigators’ analysis showed that the only factor associated with antibody response at this time was a viral load below 400 copies/ml (p < 0.03).

The vaccine appeared to be safe. Only 2% of children experienced moderate to severe side-effects (three cases of fever; one of fatigue).

Revaccination provided long-term benefits. When antibody levels were assessed 80 weeks after revaccination, the investigators found that they were at protective levels in 80% of children.

The subgroup analysis indicated  there were high levels of immunologic memory following revaccination. The children in this analysis had a median CD4 cell percentage of 35%. They received their second MMR booster dose a median of 4.24 years after initial revaccination. At this time, some 98% had detectable levels of measles antibodies, and in 75% their level was sufficient to protect against the infection. Seven days after revaccination, the proportion with protective levels of antibodies had increased to 83% and this had increased again to 95% by day 28. A response to revaccination was associated with a viral load below 400 copies/ml (p = 0.03).

None of the children undergoing this second revaccination experienced moderate or severe side-effects.

The author of an accompanying editorial believes the study “provides promising information guiding measles vaccine use among HIV-infected children”. However, she cautions that “A number of obstacles still remain to reduction of global measles infection, especially among the larger population of HIV-infected infants and children living in resource poor settings.” These include sub-optimal prevention and diagnosis of HIV; inadequate access to HIV therapy; and poor uptake of measles vaccination.

She concludes that the “study provides further evidence to support recommendations for measles booster vaccination of HIV-infected children on stable antiretroviral therapy with suppressed viral loads”, adding “This observation can only be successful in preventing measles morbidity and mortality if it is coupled globally with aggressive identification and antiretroviral treatment of children with HIV infection.”

Abzug MJ et al. Immunogenicity, immunologic memory, and safety following measles re-vaccination in HIV-infected children receiving highly active antiretroviral therapy.  J Infect Dis, online edition, 2012.

Maldonado Y et al. Measles vaccine, HIV infection, and antiretroviral therapy – a window of opportunity.  J Infect Dis, online edition, 2012.