Short Communication: Selection of Thymidine Analogue Resistance Mutational Patterns in Children Infected from a Common HIV Type 1 Subtype G Source

Abstract

In HIV-1, thymidine analogue mutations (TAMs) cluster in one of two groups (215Y, 41L, 210W, or 215F, 219E/Q), representing two independent mutational patterns (T215Y and T215F cluster, respectively). The mechanisms by which these pathways are selected are not fully understood. To investigate possible factors driving the selection of the TAMs, we analyzed the TAM patterns with regard to the respective treatment, viral load, and HLA in 18 children all infected from a common source of HIV-1 clade G virus and initially treated with zidovudine. The HIV reverse transcriptase sequences of 14/18 children carried at least one TAM. At first sampling date, the T215Y-linked pattern was observed in five cases and the T215F cluster was seen in nine. During the follow-up period, three patients changed their patterns. Children treated with identical NRTI combinations at the first sampling date developed different pathways. Under AZT/d4T therapies, an association was found between the HLA B*13 (in combination with HLA DRB1*0701) and the mutation T215Y. The mutation T215Y reverted in three out of four patients who discontinued AZT/d4T treatment. We speculate that in the context of these subtype G viruses, the development of the T215Y mutation may be strongly disfavored whereas the presence of HLA B*13 may counteract this effect and permit its development.