Clinical and biological disease progression in vertically acquired paediatric HIV infection

With available interventions in Europe, mother-to-child, or vertical transmission of HIV has been reduced from 15-20%, but still occurs in around one or two of every 100 pregnancies of HIV infected women. Progression of disease in vertically-infected children is most rapid in early life and without early treatment about one-fifth progress to serious clinical illness or die before one year of age. However, those surviving the first few years of life, including the ones with previous serious illness are generally clinically well throughout childhood, sometimes even without antiretroviral treatment. With the increasingly common use of aggressive therapy at an early stage of infection, progression to serious disease or death is now rare. Clinical disease progression is closely associated with HIV RNA viral load which peaks at around age three months, with a subsequent decline thereafter in vertically-infected children. Levels in girls are different to those of boys, but the pattern of this difference is not consistent over age. Progression of HIV infection is also related to the levels of immunological components such as CD4, CD8 and absolute lymphocyte cell counts. Patterns over age differ by both gender and race in both infected and uninfected children with absolute lymphocyte values and subsets being generally higher for girls and white children. Levels in infected children differ markedly to those of uninfected children but much of the ranges of measurements are common to both. Early-life measurements of CD4 percentage and absolute lymphocyte count independently predict rapid progression to serious disease or death during the first year of life, while early persistent hepatomegaly or splenomegaly is prognostic of serious disease progression thereafter. However, there are no differences in progression by gender and race, nor are the prognostic abilities of markers altered by gender or race, which would suggest that clinical guidelines need not account for such factors. Of the early prognostic indicators, CD4 percentage measurement is the most useful and beyond six months of age a CD4 percentage cut-off of 10% best informs subsequent disease progression risk.