Early Highly Active Antiretroviral Therapy Enhances B-cell Longevity

Background: We have previously reported that an early initiation of highly active antiretroviral therapy (HAART) in HIV-1 vertically infected children enhanced the function of memory B-cells gained during childhood routine vaccinations. On the other hand, a significant waning of immunity was observed for patients with a late treatment. In this follow-up study, we report data from a sample of patients in our cohort including late-treated patients being revaccinated with routine childhood vaccines. Methods: The levels of serum antibodies and cellular immunity were measured by antigen-specific enzyme-linked immunosorbent assay and B-cell ELISpot. Moreover, flow cytometry on the frequencies of mature-activated (CD10-CD21-) and double-negative (CD27-IgD-) B-cells as hallmarks of immune activation and immune senescence, respectively, was performed for all patients. Results: Reduced protective humoral immunity and cellular immunity to routine childhood vaccines was observed in late-treated patients. Moreover, we found that timing of HAART related with the frequencies of mature activated and double negative. Conclusions: Altogether the data presented in this follow-up study reenforce the importance for an early start of HAART in HIV-1 vertically infected individuals and suggest that timing of HAART is a fundamental factor to take into account for vaccination design in this population.