SENSITIVE DETECTION AND EARLY PROGNOSTIC SIGNIFICANCE OF p24 ANTIGEN IN HEAT-DENATURED PLASMA OF HUMAN IMMUNODEFICIENCY VIRUS TYPE 1-INFECTED INFANTS

Abstract

Purpose of Study. To investigate the effect of heat-dissociated release of complexed antigen on the sensitivity of commercial p24 antigen assays, to compare it with polymerase chain reaction (PCR) and viral culture, and to examine its prognostic utility in HIV-1 infected infants. Acid-mediated release of antigen from immune complexes is inefficient in the presence of high titers of antibody to p24 antigen.

Study Population. Six hundred ninety banked serum or plasma samples from 305 patients of a cohort were studied (median age, 11 months), including 142 samples from 53 infected patients. In addition, 113 samples from cohort children were analyzed prospectively.

Methods. Standard commercial p24 enzyme immuno-assay (EIA) with and without heat dissociation of serum prior to assay. Positive results were subjected to confirmatory neutralization. PCR and culture were performed by standard techniques.

Results. In the retrospective cohort study, the specificity of heat dissociation was 96.9% in 390 uninfected samples after initial testing and 100% after neutralization. Sensitivity among 125 postnatal infected samples was, at a detection level of 2 pg/mL, 96% (97% neutralizable) compared with 47.7% for nonheat-dissociated antigen (76% neutalizable), 96% for PCR, and 77% for viral culture. These results were confirmed in the prospective study. Symptomatic children had heat-dissociated p24 antigen levels twice that of asymptomatic patients, most noticeable in the first 2 years of life (P = .004). Four of five patients with a heat-dissociated p24 assay absorbance greater than 0.9 in the first 6 months of life died (range, 5 to 18 months of age), while only four of 15 with lower absorbance within the first 6 months died (range, 5 to 26 months), suggesting a prognostic use for this test.