HIV-positive children vaccinated against influenza have weaker protective immune response

Influenza vaccine is effective in HIV-positive children who have responded well to antiretroviral therapy, but the protective immune response is weaker than that seen in healthy HIV-negative children, according to a study appearing in the July 1^stJournal of Acquired Immune Deficiency Syndromes.

Some immune system defects persist in people who have responded well to antiretroviral therapy, and those defects appear to have the potential to compromise protective vaccine-induced immune responses. Children taking antiretroviral therapy may be able to experience greater immune restoration than their adult counterparts because of immunologic developments taking place in earlier stages of life. However, the question remains whether HIV-positive children have the immune capacity to respond in the same way as healthy children to vaccinations.

The influenza vaccine study, which took place at a University of Milan paediatric clinic, enrolled 24 HIV-positive children and 14 healthy age- and gender-matched children who served as controls. Researchers used an observational, prospective, open-label study design.

The HIV-positive study participants met the following inclusion criteria: undetectable viral load, use of antiretroviral therapy for at least six months, and no prior experience of being vaccinated against influenza. Mean time on antiretroviral therapy was 85 months, and mean age was 12.6 years.

All study participants were assessed at baseline before being given one dose (0.5 ml) of a trivalent virasome-adjuvanted influenza vaccine containing three vaccine strains: A/New Caledonia/20/99 (H1N1), A/California/7/2004 (H3N2) and B/Shanghai/361/2002. Participants were reassessed one month and six months after receiving the vaccination.

At one month, many HIV-positive and HIV-negative children met seroconversion and seroprotection criteria for all three strains, but a larger proportion of HIV-negative children had these outcomes. The seroconversion rates were 54% versus 71% of children for A/H3N2; 71% versus 93% for A/H1N1; and 71% versus 86% for B, respectively. These differences were not statistically significant.

Regarding seroprotection findings, protective A/H1N1-specific antibody titres were seen in a significantly lower proportion of HIV-positive children than HIV-negative children at baseline (≥ 1:40, 38% versus 79%; p = 0.014). The proportion of children with protective antibody titres against all three strains increased from baseline to one-month follow-up in both groups, but a higher proportion of HIV-negative children showed improvements. Better seroprotection persisted in the HIV-negative group six months after vaccination, with one difference achieving statistical significance (B-specific antibody titers; 63% HIV-positive versus 93% HIV-negative; p = 0.04).

Both groups of children displayed significant increases in geometric mean antibody titres (GMTs) against all three strains, but HIV-positive children had significantly lower A/H3N2- and A/H1N1-specific GMTs (p > 0.01). Another significant difference was found in influenza-specific IgG3 titres one month after vaccination; although these increased for both HIV-positive and HIV-negative children, a much greater overall increase could be seen in the HIV-negative group (p = 0.01).

The behaviour of T lymphocytes also varied according to HIV status. One month after vaccination, both the HIV-positive group and the HIV-negative group had significant increases in gamma interferon-producing influenza-specific CD8 T lymphocytes (p > 0.001, p = 0.02, respectively). However, the difference only remained significant for the HIV-negative group at six months (p > 0.01). Furthermore, only the HIV-negative group had a statistically significant increase in the number of IL-2-producing influenza-specific CD4 T lymphocytes (p > 0.001 at months 1 and 6 compared to baseline).

“The persistence of immune defects in HIV-infected children prevents the possibility of mounting fully efficient immune responses to vaccination,” the authors conclude. “The efficacy of different, more frequent and/or more intense vaccine schedules should be considered in these children.”

The fact that the HIV-positive children in the study had very low viral loads and normal CD4 cell counts points to a need for a better understand of the persistence of some immune impairments in the face of therapeutic success. Citing a number of additional studies, the authors observe: “Whereas it was convincingly shown that [antiretroviral therapy] can restore CD4 T-cell counts to an almost optimal degree, functional immune defects are much less susceptible to being fully reverted by therapy.”