New mutations associated with resistance not detected following zidovudine monotherapy in pregnancy when used in accordance with British HIV Association guidelines*

Abstract

To determine whether mutations conferring drug resistance are detectable after zidovudine monotherapy (ZDVm) in pregnancy, using both standard genotyping and more sensitive cloning assays. Post-delivery samples from women meeting the British HIV Association guidelines criteria for the use of ZDVm in the prevention of mother-to-child transmission (MTCT) and who received ZDVm were analysed using the Trugene HIV-1 genotyping assay. In order to detect drug-resistant minority species, samples from a sub-group of 14 women were evaluated for minority drug-resistant variants. Nested polymerase chain reaction (PCR) products from the reverse transcriptase (RT) gene (codons 1-258) were cloned into the pCR4 Blunt TOPO cloning vector. Sequences were submitted to the Stanford University HIV Drug Resistance Database for analysis. Eighty women met the inclusion criteria. Successful genotypes were obtained from 53. There were no new mutations conferring resistance to ZDV detected post-delivery using either standard genotyping or cloning for minority species. A short course of ZDVm in carefully selected women does not lead to the emergence of drug resistance based on either standard genotyping or cloning for the detection of minority species. Therefore, this strategy can still be considered in women wishing to prevent MTCT while minimizing antiretroviral exposure, without fear of compromising their future HIV care.