MCV4 appeared safe, immunogenic in adolescents with HIV

The quadrivalent meningococcal conjugate vaccine appeared safe for use and effective at preventing disease in adolescents with HIV, although response rates still remained lower than in healthy children, according to recent study results.

Researchers from several institutions conducted a phase-1/2 trial — P1605 — at 27 sites in the IMPAACT network from July 2007 to October 2007 to determine the safety and efficacy of quadrivalent MCV4 (Menactra, Sanofi-Pasteur) in children infected with HIV.

“The Advisory Committee on Immunization Practices has acknowledged the potential benefit of giving MCV4 to HIV-infected children and adolescents, since HIV infection likely increases the risk of meningococcal disease,” the researchers wrote. “In addition, most perinatally acquired and all new adolescent cases of HIV infection in the United States are age-eligible for MCV4. However, there are no data regarding the use of MCV4 in HIV-infected patients of any age.”

The study population was composed of patients with HIV aged 11 to 24 years who had no personal or family history of Guillain-Barré syndrome. They also had to be on stable antiretroviral therapy or not receiving ART for at least 90 days before immunization, the researchers said. Additionally, only patients who had not received MCV4 within the past two years qualified for inclusion.

The researchers administered MCV4 at study entry, and, at 24 weeks, children with CD4 less 15% received second doses. Patients with 15%, 24% or at least 25% CD4, however, were randomly assigned to either receive second or no additional doses.

Results indicated that 3.1% of 319 study participants experienced local vaccine reaction adverse events after administration of the first dose, with most children reporting pain and tenderness at the injection site. These adverse reactions, however, were mild, and only 2.2% of children had grade 3 events or worse. These problems also appeared unrelated to MCV4, the researchers noted, and no deaths were reported within 42 days of immunization.

Serologic data were available for 305 children with a median age of 17 years. Data showed that 41% demonstrated baseline immunity to serogroup A; 11% to C; 15% to W-135; and 35% to Y. Postvaccination response rates also varied according to serogroup, the researchers reported, with 68% having immunity to A; 52% to C; 73% to W-135; and 63% to Y.

The researchers also said lower entry CD4 percentage, higher viral load and CDC Class B/C diagnosis were predictors of lower immunogenic response to serogroup C.

“The association of higher VL (viral load), lower CD4% and more advanced HIV disease stage with lower odds of vaccine response was consistent across all four serogroups contained in the MCV4 vaccine, and all remained independently and strongly associated with vaccine nonresponse in the multivariable model,” the researchers wrote.

A single dose of MCV4 was safe and produced immunogenicity in children infected with HIV according to results, but they said their study had limitations and encouraged future study in this area.

This article highlights that adolescents with HIV respond to quadrivalent meningococcal conjugate vaccines well with few associated adverse events after vaccination. Although the study did not enroll adolescents with HIV and a direct comparison of the immune responses between infected and uninfected subjects cannot be made, historical data suggest that the immune responses in the patients with HIV are likely somewhat less than in those seen in the uninfected. Variables in the patients with HIV that were associated with significantly lower immune responses were low CD4 counts, elevated viral loads, and CDC Class B/C diagnoses, as would be expected.

– Kathryn Edwards, MD
Vanderbilt University

Siberry GK. Pediatr Infect Dis J. 2010;29:391-396.