Children receiving ART may benefit from revaccination

Sutcliffe CG. Lancet Infect Dis. 2010;10:630-642.

Many children with HIV who initiated antiretroviral therapy experience waning immunity after vaccination, and booster doses later in life may play an important role in preventing disease, researchers from the Johns Hopkins Bloomberg School of Public Health in Baltimore noted in a study published this week.

There are currently no recommendations on revaccination of children with HIV.

“Immune reconstitution in children is primarily through the generation of naïve T cells rather than expansion of memory T cells, as in adults,” wrote William J. Moss, MD, and colleagues. “Consequently, [antiretroviral therapy] might not restore vaccine-induced immunity established before the start of therapy.”

The researchers reviewed 38 studies that examined the duration of protective immunity conferred by vaccination in children with HIV who are receiving antiretroviral therapy (ART). Short-term immunity was defined as protection lasting 3 months or less while long-term immunity was defined as protection lasting longer than 3 months.

Non-replicating vaccines, such as the diphtheria tetanus pertussis vaccine (DTP), hepatitis B vaccine (HepB), pneumococcal vaccines and conjugate Haemophilus influenzae type b vaccines (Hib), were examined in several studies, while others analyzed live vaccines, such as the measles, mumps and rubella vaccine.

Several studies analyzing these non-replicating vaccines suggested a positive link between immunity and vaccination after initiating ART at an older age, while beginning treatment at a young age correlated with loss of immunity. The researchers found similar results among studies involving live vaccines, noting that seropositivity appeared higher before ART initiation.

Studies of DTP, conjugate Hib, HepB, pneumococcal and inactivated influenza vaccines also examined the effects of revaccination in children who were immunized before starting ART. Data demonstrated decreases in immunity among this population after the first vaccination, although a high number of children maintained immunity for approximately 1 year.

Revaccination occurred after a median of 4.6 years in these studies. Results indicated that 37% of children who were seronegative within 1 week of revaccination seroconverted after 4 weeks, the researchers said.

Research on live vaccines primarily involved revaccination with vaccines received before initiation of ART. Children generally responded well and achieved some level of immunity, according to the researchers, yet the protection appeared to drop off over time in long-term studies.

“These results suggest that children on [ART] would benefit from revaccination, but levels of protective immunity might need to be monitored and some children may need additional vaccine doses to maintain protective immunity,” Moss said in a press release.

Antibody and lympoproliferative responses to revaccination also appeared adequate in children receiving ART, according to the data.

The researchers noted that predictors for immunity could not be pinpointed. However, age of ART initiation in relation to timing of vaccination may be a factor. Results from one study indicated that children who began treatment in infancy had greater protective immunity that was nearly on par with children who did not have HIV.

“Early administration of [ART] preserved the memory B-cell compartment,” wrote the researchers. “The restoration of immune function in infants on [ART] might be similar to the immunological benefits noted among adults treated during acute infection.”

The researchers also noted many children who began ART early were most likely immunized after they were already receiving treatment and therefore had a higher likelihood of achieving immunity from vaccination.

“For all vaccines studied, immune reconstitution seems to have allowed this group to both preserve immune responses to previously received vaccines and successfully mount and maintain an immune response to new vaccines,” the researchers wrote. “These findings support recommendations for early administration of [ART] among infants, which reduces HIV-related morbidity and mortality.”

They pointed out, however, that gaps in knowledge remain, and the best timeline for vaccination or revaccination remains unclear.

“Continued efforts are needed to identify and treat HIV-infected children at younger ages and at earlier stages of disease,” said study researcher Catherine Sutcliffe, PhD. “Vaccination policies and strategies for children infected with HIV and on [ART] should be developed in regions of high HIV prevalence to ensure adequate individual and population immunity. Without such recommendations, as treatment programs scale up and more children receive [ART] and live into adolescence and adulthood, a larger proportion of these children could be susceptible to childhood diseases.”

There are precious few studies examining the level and duration of vaccine-specific immune responses following administration of either inactivated or live-attenuated vaccines in immune compromised hosts. This study provides guidance based on solid findings - a breath of fresh air in a situation that is often driven by recommendations in the absence of data.

– Paul Offit, MD

Children's Hospital of Philadelphia

Philadelphia, PA