AEGiS-14IAC: Identification of polymorphisms and silent mutations at sites associated with resistance to inhibitors of transcriptase (RT) and protease (PR) in HIV-1 clade C isolates.

14th International AIDS Conference


Barcelona, Spain - July 7-12, 2002

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Identification of polymorphisms and silent mutations at sites associated with resistance to inhibitors of transcriptase (RT) and protease (PR) in HIV-1 clade C isolates.

Int Conf AIDS 2002 Jul 7-12; 14:(abstract no. ThOrA1433)

Loemba HD, Brenner B, Ma'ayan S, Spira B, Moisi D, Oliveira M, Detorio M, Essex M, Wainberg MA
McGill University AIDS Centre, LDI, Jewish General Hospital, Montreal, Canada

BACKGROUND: To study the potential impact of HIV-1 clade C genetic diversity on emergence of drug resistance.

METHODS: The subtype origin of HIV-1 isolates from 9 drug-naïve patients from Botswana and 5 from Ethiopia was determined by heteroduplex mobility assays (HMA) of the envelope gene and sequencing of RT and PR regions. Resistant viruses to non-nucleoside RT inhibitors (NNRTIs), including nevirapine (NVP), delavirdine (DLV) and efavirenz (EFV), were selected in tissue culture assays. Phenotypic and genotypic variations in clade C isolates were compared to clade B controls .

RESULTS: Phylogenetic analysis revealed that all tested isolates from Botswana and Ethiopia were of subtype C. Various pre-existing mutations associated with resistance to RT and PR inhibitors were detected. All subtype C RTs contained a specific KVEQ motif of silent mutations at sites corresponding to codons 65, 106, 138 and 161 respectively and associated with resistance to NRTIs and NNRTIs . A silent mutation A(GCC) to A(GCT) found at codon 62 mutated to A62V, i.e. A(GCT) to V(GTA), following DLV selection. This mutation is associated with NRTI multi-drug resistance. Similarly, EFV selection resulted in a novel mutation V106M, i.e. V(GTG) to M(ATG), at a site conferring NNRTI multi-drug primary resistance. At this site, a silent mutation V(GTA) to V(GTG) was pre-existing.

CONCLUSIONS: These findings suggest that silent mutations and polymorphisms in clade C viruses could impact on the development of drug resistance.

Keywords: AEGIS, HIV-1, HIV-1 Reverse Transcriptase, Mutation, Polymorphism (Genetics), HIV Infections, HIV Protease, Oxazines, Nevirapine, DNA-Directed RNA Polymerases, Variation (Genetics), Endopeptidases, Botswana, Ethiopia, efavirenz, Human, geneticsKWDaegis,hiv-1,hiv-1reversetranscriptase,mutation,polymorphism(genetics),hivinfections,hivprotease,oxazines,nevirapine,dna-directedrnapolymerases,variation(genetics),endopeptidases,botswana,ethiopia,efavirenz,human,genetics

020707
ThOrA1433

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