Effect of changing antiretroviral therapy on human immunodeficiency virus viral load: experience with fifty-four perinatally infected children

Background, Experience in adults has shown that combination therapy includi ng HIV protease inhibitors (PI) can profoundly affect viral replication and slow progression of HIV-associated disease. Trials defining the influence of PI and combination therapies on long term outcome of HIV infection in ch ildren have not yet been completed, Experience with infants and children wh o were receiving routine care in an HIV specialty clinic was reviewed to ch aracterize the effect of changes involving one, two or three antiretroviral s. Methods. Clinical and laboratory findings of children in whom antiretrovira l therapy was changed were retrospectively reviewed. Successful response wa s defined as a reduction of viral load of at least 0.7 log(10) RNA copies/m l lasting for at least 3 months. Differences in characteristics and the cha racter of the response associated with successful and unsuccessful changes were analyzed. Results, Of the 72 changes in therapy that were made in 54 children, 29 res ulted in a successful response. A change involving 3 antiretrovirals was mo re likely to produce a successful response than a change involving 1 agent (6 of 9 vs. 6 of 24; P < 0.04). Reduction of viral load by > 100-fold or to undetectable amounts occurred more frequently in children who responded to a regimen containing a PI than in children who responded to reverse transc riptase inhibitors (11 of 21 vs. 1 of 8; P = 0.05). Furthermore successful responses associated with addition of a PI were associated with a greater r eduction in viral load than those that involved reverse transcriptase inhib itors (1.63 +/- 0.60 vs. 0.99 +/- 0.12 log(10); P = 0.003), Conclusions, This experience suggests that changing antiretroviral therapy in HIV infected children to regimens containing three drugs is more likely to result in a successful virologic outcome than changes in therapy involvi ng one drug. This experience further supports the conclusion that including a PI as part of an antiretroviral regimen is more likely to result in a gr eater reduction in viral load in children.