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UBC Theses and Dissertations

Virologic studies in pediatric HIV-1 infection Binns, Christine Ruth


The proportion of HIV-1-infected children is increasing in parallel with that of women of child-bearing age. There are currently over 200 HIV-1-infected Canadian children. This study was undertaken with the main objective being to evaluate several clinical and laboratory measures in this population to gain a better understanding of their disease status and their risk for progressing to AIDS. These measures included viral load testing, drug resistance testing, CD4+ T cell levels, and viral phenotype testing. It was hypothesized that a group of clinical and/or laboratory tests exist which would be optimal markers by which to assess a pediatric HIV-1 patient's current status as well as the risk of disease progression over time. Secondary objectives included to determine the prevalence of resistance to zidovudine (ZDV) in HIV-1-infected Canadian children and to determine the association of drug resistance with the other clinical and laboratory variables evaluated. HIV-1-infected pediatric patients were recruited from seven healthcare centers across Canada. Plasma and peripheral blood mononuclear cells (PBMCs) were isolated from whole blood samples donated by these patients. Plasma viral load determinations were performed. PBMCs were co-cultured to generate viral stocks from which viral phenotype and standardized ZDV resistance testing assays were performed. PBMCs were also used to set up quantitative micrococultures which were used as the basis for our rapid phenotypic resistance assay and for determining cell-associated viral loads. Data was available for a total of 86 patients. 23/78 (30%) HIV-1 positive viral isolates were of the SI phenotype. 14/60 (23%) isolates showed resistance to ZDV according to the rapid phenotypic resistance assay. Median cell-associated viral load was 125 IU/106 cells and median plasma viral load was 25000 copies/ml. 26/53 (49%) isolates showed resistance to ZDV according to the genotypic resistance assay. A positive correlation was observed between cell-associated and plasma viral load (r=0.37, p=0.004). Plasma viral load and the presence of encephalopathy were also highly correlated (p=0.023), as were plasma viral load and perinatal transmission (p=0.004). In contrast, cell-associated viral load tended to be higher in children without encephalopathy and who had acquired HIV-1 non-perinatally (highly significant (p=0.001)). 35/45 (78%) of the samples on which comparative analysis of genotypic and phenotypic resistance was performed produced concordant results. Phenotypic resistance, genotypic resistance, and SI phenotype were found to be correlated with lower CD4 cell counts and percents. According to the results obtained in this study, the prevalence of ZDV resistance among HIV-1-infected Canadian children is high. It is surprising that more significant associations between different parameters were not found in establishing this "viral inventory". Associations may become more clear as prospective data are obtained.

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