Emergence of resistance in children treated with ddI/d4T after treatment to reduce MTCT
Polly Clayden, HIV i-Base
The main obstacle to using short course and single dose antiretrovirals as an intervention to reduce MTCT is the development of resistance not only for the mothers but also for the infected infants.
One study, first presented in Durban, looked at different nucleoside regimens from the most frequently used drugs used in MTCT programmes . In this trial, women were randomised to four arms and received d4T; ddI; d4T plus ddI and ZDV from 34/36 weeks of gestation until delivery. In addition infants received the same drugs as their mothers within 36 hours of birth and continuing for a six weeks, and infants received off study ddI plus d4T after the six week study period.
A poster presented in Barcelona looked at resistance data from 22 infected infants from this study, that showed no evidence of resistance mutations associated with any of the drugs used at of six-12 weeks of age . One of the infants had the A98G mutation, which is associated with low level nevirapine resistance. This mutation was also evident in the child’s mother who did not report having ever received nevirapine, so is therefore likely to be a naturally occurring polymorphism of HIV-1 subtype C viruses.
Samples were available for 12/22 of the infants at nine-18 months who had received off ddI and d4T study. Of this group six infants had evidence of resistance – five had the rarely reported T69N mutation conferring low-level resistance to ddI and potential low-level resistance to d4T. Two had the Q151M mutation associated with multi-nucleoside resistance and one had the V75I, F77L and F116Y mutations associated with multi-nucleoside resistance.
The investigators concluded that ‘These data indicate that HIV-1 infection in infants is not due to the transmission of drug resistant virus following short-course therapy with ddI, d4T and AZT. However continued therapy with ddI plus d4T was associated with resistance in half of the infants.’
- Gray G et al. Preliminary efficacy, safety, tolerability and pharmacokinetics of short course regimens of nucleoside analogues for the prevention of mother to child transmission of HIV. Programme and Abstracts XIII International AIDS conference, Durban, Abstract TuOrB35
- Pillay C, Gray G, Stevens G et al. Emergence of resistance mutations in children treated with ddI plus d4T after treatment to prevent mother-to-child transmission Program and Abstracts XIV International AIDS Conference Barcelona 2002. Abstract TuPeB4583