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Longitudinal follow-up of pediatric human immunodeficiency virus infection Baker, Jennie N.


This longitudinal follow-up study was undertaken to document the clinical history of virologic parameters in HIV-infected children, including the evolution of resistance to the antiretroviral agents zidovudine and lamivudine. The effect of differing therapeutic regimens on these parameters was studied. Nine pediatric patients from the Oak Tree Clinic in Vancouver were evaluated. Serial CD4 cell counts, plasma viral loads and all combinations of antiviral therapy were recorded from the time of diagnosis. Results showed that eight out of nine patients received either single or double drug combinations as initial therapy and the remaining patient was started on a triple combination therapy regimen. At last follow-up, the median viral load was 2,415 copies/mL and the median CD4 count was 765 cells/μL. The median change in viral load from baseline was -53,180 copies/mL and CD4 count was +54 cells/μL. For the entire observation period, only four cases achieved undetectable plasma viral loads. Of these four, there is only one case of durable suppression, this being the only patient to start on a triple drug regimen. Sequencing showed that 7/9 patients carried isolates that were AZT resistant. Of the two patients with susceptible isolates, one is on triple therapy and the other remains on dual therapy (including AZT) with a viral load of 16,000 copies/mL. There were six cases of 3TC resistance, with three patients carrying susceptible isolates. Of these three, one is no longer on the drug and another is the maximally suppressed, receiving triple combination therapy as the initial regimen. Studies in adults have shown that dual combination therapy is inadequate in suppressing viral replication and preventing the evolution of drug resistance and disease progression. It is during the developmental stages of childhood that adequate antiretroviral therapy will have its greatest impact in minimizing the neurodevelopmental effects of HIV disease. Thus, triple combination regimens must be selected to achieve maximal virologic containment and minimize the development of antiretroviral resistance.

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