Study of Human Immunodeficiency Virus Resistance to 2′-3′-Dideoxyinosine and Zidovudine in Sequential Isolates from Pediatric Patients on Long-Term Therapy

Resistance to zidovudine (3′-azido-3′-deoxythymidine) and 2′,3′-dideoxyinosine (ddI) has been reported for human immunodeficiency virus (HIV) isolates from adults, but little is known about these drugs in children. A new micrococulture assay was developed for evaluation of drug susceptibility using single-passage HIV isolates cocultured with peripheral blood mononuclear cells from healthy donors. HIV isolates from children treated with zidovudine or ddI were evaluated to define the emergence of resistance to these antiretroviral agents. Four patients were treated with ddI and 3 with zidovudine for >15 months. There was a ⩾20-fold decrease in susceptibility to ddI for sequential isolates ofHIV recovered from 4 patients treated with ddI for 22-31 months and a 4- to 10-fold decrease in susceptibility to zidovudine in 3 patients. HIV isolates from 3 patients treated with ddI or zidovudine alone showed a minor amount of cross-resistance to the other antiretroviral agent. Results indicate the importance of monitoring antiretroviral drug susceptibility of HIV isolates when assessing clinical deterioration in children treated for >1 year.