AEGiS-04CROI: Zidovudine associated resistance mutations among zidovudine treated Thai adults infected with HIV-1 subtype E.

4th Conference on Retroviruses and Opportunistic Infections


Washington, DC - January 22-26, 1997

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Zidovudine associated resistance mutations among zidovudine treated Thai adults infected with HIV-1 subtype E.

Conf Retroviruses Opportunistic Infect 1997 Jan 22-26; 4th:172 (abstract no. 581)

Sirivichayakul S, Du B, Gillis J, Terwilliger E, Phanuphak P, Hammer S; Chulalongkorn University, Bangkok, Thailand.

Objective: To characterize the zidovudine (ZDV) associated resistance mutations in HIV-1 E subtype strains derived from ZDV treated Thai adults.

Methods: Peripheral blood mononuclear cells (PBMCs) were harvested from five HIV-1 subtype E-infected patients pre- and 8-24 months post-ZDV initiation. HIV-1 isolates were recovered using a standard ACTG macrococultivation protocol. Culture supernatants were titrated and ZDV susceptibility was determined using the ACTG/DoD consensus assay. The entire 1.7 kb reverse transcriptase (RT) coding region was amplified from PBMC extracts by PCR and then sequenced by standard dideoxy methods.

Results: Diminished phenotypic ZDV susceptibility was seen in 4/4 patients treated for greater than or equal to 20 months. All resistant post-treatment subtype E isolates in this study had 4 of the 5 classically described ZDV associated resistance mutations at residues 67,70,215,219. As has been described with subtype B, two isolates had a pre-treatment K70R. However, in contrast to subtype B, a different baseline and post-ZDV mutation (m) was observed at position 245 (E245K). Additionally, all resistant subtype E isolates remained wildtype (wt) at residues 41 and 210. (Table: see text)

Conclusion: Although genotypic similarities conferring ZDV resistance exist between HIV-1 subtypes E and B, unique baseline and mutational features within the subtype E RT coding region may be present. The significance of the E245K substitution is being investigated by site directed mutagenesis.

Keywords: AEGIS, Zidovudine, HIV-1, Anti-HIV Agents, HIV-1 Reverse Transcriptase, Reverse Transcriptase Inhibitors, Mutation, RNA-Directed DNA Polymerase, Adult, Human, genetics, AIDSKWDaegis,zidovudine,hiv-1,anti-hivagents,hiv-1reversetranscriptase,reversetranscriptaseinhibitors,mutation,rna-directeddnapolymerase,adult,human,genetics,aids

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Copyright © 1980, 1997 - Foundation for Retrovirology and Human Health. Reproduction of this abstract (other than one copy for personal reference) must be cleared through the Foundation for Retrovirology and Human Health. Licensed through AIDSLINE, National Library of Medicine.