Quantitative Human Immunodeficiency Virus (HIV)-1 Antibodies Correlate With Plasma HIV-1 RNA and Cell-associated DNA Levels in Children on Antiretroviral Therapy

Abstract

Background: This study measured serial plasma human immunodeficiency virus (HIV)-1-specific antibody (Ab) levels in children who initiated antiretroviral therapy (ART) prior to 2 years of age, and evaluated their relationship to peripheral blood HIV-1 RNA and DNA levels.

Methods: We studied 46 HIV-1-infected children, stratified by age at ART initiation (<3 mo, early therapy [ET]; >3 mo-2 years, late therapy [LT]) and by virologic response (R) or non-response (NR), before and up to 4 years following ART. We studied 20 HIV-1-uninfected children born to HIV-1-infected mothers (seroreverters [SR]) as controls. Plasma immunoglobulin G (IgG) Ab levels directed against HIV-1 envelope (gp160, gp41), gag (capsid, p24; matrix, p17), reverse transcriptase (p66/51), and integrase (p31) were serially measured using quantitative enzyme-linked immunosorbent assays. HIV-1 Ab rates of decline were estimated over the first 15 months of the study.

Results: The HIV-1 Ab rates of decline in the ET-R group were similar to those in the SR group for all Ab specificities, except for p17 (P = .01). Ab decline rates in the LT-R group and the NR group were significantly slower than in the SR group for all tested Ab specificities. After 1 year of age, Ab levels to p31 and p17 were significantly associated with HIV-1 RNA levels (P < .001); Ab levels to gp160 (P < .001) and gp41 (P < .001) were significantly associated with cell-associated HIV-1 DNA levels.

Conclusions: Quantitative HIV-1-specific Ab levels may be useful for screening children on ART for viral suppression or for residual, cell-associated HIV-1 DNA levels.

Clinical trials registration: NCT00000872.

Keywords: HIV-1 persistence; HIV-1 quantitative antibodies; pediatric early antiretroviral therapy.

Figure 1.

Human immunodeficiency virus (HIV)-1–specific antibody (Ab) decay rates in HIV-1–uninfected infants born to HIV-1–infected women (SR) in ET-R and LT-R groups. Quantitative (Quant) Ab levels of HIV-1 gp160, gp41, RT, p24, p31, and p17 in SR, ET-R, and LT-R children over the first 24 months of age. Ab decline rates, calculated over the first 15 months, in the ET-R group are similar to the SR group for all Ab specificities, except for p17 (P = .01). Fitted lines for the SR and ET-R groups were calculated with parameters from the linear mixed effects model. SR are shown as blue circles; ET-R as red squares; and LT-R as black, hollow squares. Abbreviations: Ab, antibody; ET, early therapy; HIV, human immunodeficiency virus; LT, late therapy; OD, optical densities; Quant, quantitative; R, viral responders; SR, seroreverters.

Figure 2.

Prediction of human immunodeficiency virus (HIV)-1 RNA and DNA based on linear and logistic models using quantitative antibody levels as predictors. A, Coefficient plot: coefficients and the 95% confidence intervals for the antibody (Ab) specificities, derived from a linear regression model predicting HIV-1 RNA levels (c/ml) from Ab levels. Bars which do not cross the line at 0 indicate a significant predictor. Model results: F(6,134) = 36; P < .001; R² = 0.62. B, The estimated probability of detectable HIV-1 RNA (>50 c/ml) based on Ab levels of p31 derived from the logistic model. C, Coefficient plot: coefficients and the 95% confidence interval for the Ab specificities, derived from a linear regression model predicting HIV-1 DNA levels (c/million peripheral blood mononuclear cell) from Ab levels. Bars which do not cross the line at 0 indicate a significant predictor. Model results: F(6,61) = 7.1; P < .001; R² = 0.41. D, The estimated probability of HIV-1 DNA > 1000 based on Ab levels of gp160 derived from the logistic model. Abbreviations: Ab, antibody; ELISA, enzyme-linked immunosorbent assay; HIV, human immunodeficiency virus; OD, optical densities; PBMC, peripheral blood mononuclear cell; Pr, probability; RT, reverse transcriptase.