Age- and time-related changes in extracellular viral load in children vertically infected by human immunodeficiency virus.

BACKGROUND It is known that plasma or serum viral load is high in vertically HIV-infected children during the first year of life, but the changes in these titers after the first birthday have not been described. Information on the natural history of circulating extracellular virus will be useful in elucidating the pathogenesis of pediatric HIV infection and in using viral load measurement to guide prognosis and therapy. METHODS We measured serum RNA by reverse transcriptase-polymerase chain reaction and immune complex-dissociated p24 antigen enzyme-linked immunosorbent assay over time in 48 unselected children followed in our clinics and analyzed the findings in relation to age and clinical outcome. RESULTS In first-available samples from the 48 children there was a gradual reduction in HIV RNA values with increasing age, with a slope of -0.21 log copy/ml/year (P < 0.001, R2 = 0.6022). This downward trend was seen in subsets of children with all degrees of immunodeficiency. The mean slope of repeated HIV RNA measurements in individual children was similarly in a downward direction (slope -0.11 (P = 0.007 for difference from zero)). The slope was more negative in children who were younger at baseline. Immune complex-dissociated p24 antigen values were much less predictable and predictive. CONCLUSIONS Viral load in vertically infected children, measured by reverse transcriptase-polymerase chain reaction, falls very gradually over time, descending from very high titers at the end of the first year, and reaching values seen in horizontally infected adults at approximately 5 years of age.

[1]  P. Hartigan,et al.  Changes in plasma HIV-1 RNA and CD4+ lymphocyte counts and the risk of progression to AIDS. Veterans Affairs Cooperative Study Group on AIDS. , 1996, The New England journal of medicine.

[2]  M. Giacca,et al.  Dynamics of viral replication in infants with vertically acquired human immunodeficiency virus type 1 infection. , 1996, The Journal of clinical investigation.

[3]  J. Mellors,et al.  Quantitation of HIV-1 RNA in Plasma Predicts Outcome after Seroconversion , 1995, Annals of Internal Medicine.

[4]  S. Kwok,et al.  Viral measurement by polymerase chain reaction-based assays in human immunodeficiency virus-infected infants. , 1995, The Journal of pediatrics.

[5]  A. Perelson,et al.  Rapid turnover of plasma virions and CD4 lymphocytes in HIV-1 infection , 1995, Nature.

[6]  Martin A. Nowak,et al.  Viral dynamics in human immunodeficiency virus type 1 infection , 1995, Nature.

[7]  I. Chen,et al.  Rapid increases in load of human immunodeficiency virus correlate with early disease progression and loss of CD4 cells in vertically infected infants. , 1994, The Journal of infectious diseases.

[8]  J. Sninsky,et al.  Rapid and simple PCR assay for quantitation of human immunodeficiency virus type 1 RNA in plasma: application to acute retroviral infection , 1994, Journal of clinical microbiology.

[9]  L. Mofenson,et al.  Effect of intravenous immunoglobulin (IVIG) on CD4+ lymphocyte decline in HIV-infected children in a clinical trial of IVIG infection prophylaxis. The National Institute of Child Health and Human Development Intravenous Immunoglobulin Clinical Trial Study Group. , 1993, Journal of acquired immune deficiency syndromes.

[10]  S. J. Clark,et al.  High levels of HIV-1 in plasma during all stages of infection determined by competitive PCR. , 1993, Science.

[11]  R. Koup,et al.  Deficient human immunodeficiency virus type 1-specific cytotoxic T cell responses in vertically infected children. , 1991, The Journal of pediatrics.

[12]  M. Salimans,et al.  Rapid and simple method for purification of nucleic acids , 1990, Journal of clinical microbiology.

[13]  B. Walker,et al.  HIV-specific cytotoxic T lymphocytes in seropositive individuals , 1987, Nature.

[14]  W M Moore,et al.  Physical growth: National Center for Health Statistics percentiles. , 1979, The American journal of clinical nutrition.

[15]  C. Alford,et al.  Comparative serial virologic and serologic studies of symptomatic and subclinical congenitally and natally acquired cytomegalovirus infections. , 1975, The Journal of infectious diseases.