Allen UD, Conway B, Lapointe N, King SM, Read S, Forbes J, Moore D, Gilmour J, Wells G, Bortolussi B, Cassol S, Marshall C, Tobin J; International Conference on AIDS.
Int Conf AIDS. 1996 Jul 7-12; 11: 311 (abstract no. Th.B.4353).
Tobin J
Objectives: To assess the extent of zidovudine (ZDV) resistance and to determine the association between resistance and clinical, virologic and epidemiologic variables among HIV-infected Canadian children. Methods: Subjects were recruited from 7 Canadian centres affiliated with the CPARG. Collectively, these centres follow greater than 90% of HIV-infected children in Canada. Epidemiologic, clinical and laboratory data were collected on all subjects. Mononuclear cells from anticoagulated blood from each subject were isolated by density gradient centrifugation. Quantitative cultures were performed with and without 5 micromolars of zidovudine for 14 days; a reduction in viral titre in the presence of drug was taken as a marker of susceptibility. Resistance testing was confirmed on selected isolates using genomic testing and the ACTG consensus protocol. Laboratory analyses were done without knowledge of the clinical status of the subjects. Results: To date complete data on ZDV resistance have been obtained from 73 of 98 subjects enrolled. Of these 73 subjects, 68% had perinatally-acquired and 32% had transfusion-related infection. The country of maternal birth was Canada in 51%. The mean age was 7.6 yrs (sd plus or minus 5.3). 83% of subjects had symptomatic HIV disease. The mean CD4 count was 485/mm3 (sd. plus or minus 560). The mean duration of ZDV treatment was 16.3 months (sd. plus or minus 17.1). ZDV-resistance was found in 24.7% (18/73), while 11.0% (8/73) had intermediate susceptibility. The majority of resistant isolates (82%) occurred among children on uninterrupted ZDV therapy for greater than or equal to 12 months. Mean values for haematologic parameters among those with resistant isolates versus those with sensitive isolates were: CD4 436 vs 503/mm3; CD8 847 vs 974/mm3; CD3 1325 vs 1467/mm3; haemoglobin 106 vs 114 g/L and platelets 227 vs 274 x 109/L; though lower values were consistently occurred in the group with ZDV resistance, these relationships were not statistically significant. Summary: Approximately 25% of children analyzed (or a minimum of 18.4% of those enrolled) had zidovudine-resistant HIV. There was a trend for resistance to be associated with prolonged ZDV therapy and to a lesser extent hematological markers of advanced disease. Survival patterns among subjects with and without ZDV-resistant HIV will be examined. Given the emerging problem of ZDV resistance, a revision of antiretroviral treatment strategies is warranted in Canada.
Publication Types:
Keywords:
- AIDS Vaccines
- Acquired Immunodeficiency Syndrome
- CD4 Lymphocyte Count
- Canada
- Child
- HIV Infections
- HIV Seropositivity
- Humans
- Zidovudine
Other ID:
UI: 102220632
From Meeting Abstracts