Background:  Standard clinical laboratory measures of HIV-1 disease status are viral load and CD4 count. Disease progression-associated changes in these signal post hoc an immune system that has failed for HIV-1. More sensitive pre hoc measures are needed to better monitor and direct treatment.

Methods:  A study was made of 60 HIV-1-infected children and adolescents (9, 33, 18; < 2, 2 to 10, > 10 years old) attending a clinic in Houston, Texas. Outcomes included measurement by isotype of number of antibody secreting cells in peripheral blood (a measure of B-cell activation) and capacity of peripheral blood mononuclear cells (PBMC) to undergo in vitro replication spontaneously or in response to mitogen or selected microbial antigens including HIV-1 antigens (measure of T-cell function and memory). Comparison of groups was by 2-tailed Mann Whitney and Wilcoxon methods.

Results:  Outcomes were stratified as functions of groupings on patient viral load (< 400, 400 to < 10⁴, 10⁴ to < 10⁵, ≥ 10⁵ copies/mL), CD4 level (< 15%, 15 to 25%, >25%), CD4/CD8 ratio (< 1.5 or ≥ 1.5), and age (< 2, 2 to 10, > 10 years). Antibody secreting cells changed markedly as viral load increased; there were by isotype unique patterns. Patients with undetectable viral load had low levels of antibody secreting cells/10⁶ MNC whereas those with > 10⁵ viral load (median 226,000) had high levels of activation (564 vs 2365, 215 vs 1642, 775 vs 2010, for IgA, IgM, and IgG, respectively; bold p ≤ 0.05). Progression from undetectable to about 10⁴ was paralleled by a > 3-fold increase in IgG antibody secreting cells in the absence of increases in the other isotypes; further progression to about 10⁵ associated with a selective 5-fold increase of IgM only and increase to > 10⁵ viral load linked with increases in all isotypes. LPA responses differed as a function of increasing viral load group and presence and type of stimulant (no change with no stimulant; decrease for mitogen and microbial antigens; moderately increase for HIV-1 antigens). Stratification on the other classifications identified patterns of response that differed both as functions of the category and in a pattern different from that identified by viral load or CD4.

Conclusions:  Expanding the immunologic assessment of pediatric/adolescent patients to include measurements of type and quantity of PBMC activation and function revealed changes in immunological status not revealed through application of conventional measures. These measures may provide improved epidemiological classifications and guides to patient management.

Keywords: Pediatric; Lymphocyte; ASC