AEGiS-13IAC: Selection by azt and rapid replacement in the absence of drugs of HIV-1 resistant to multiple nucleoside analogs.

13th International AIDS Conference


Durban, South Africa - July 9-July 14, 2000

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Selection by azt and rapid replacement in the absence of drugs of HIV-1 resistant to multiple nucleoside analogs.

Int Conf AIDS 2000 Jul 9-14; 13:(abstract no. TuOrA351)

Lukashov V, Huismans R, de Boer R, Goudsmit J
V. Lukashov, Meibergdreef 15, 1105AZ Amsterdam, Netherlands, Tel.: +31 20 566 58 61, Fax: +31 20 691 65 31, E-mail: v.lukashov@amc.uva.nl

OBJECTIVE: To study the evolution and fitness of multidrug-resistant HIV-1 with an insertion of two amino acids between positions 68 and 69 of the RT gene and aa changes at positions 67 and 215 in an individual receiving intermittent therapy.

METHODS: 17-20 full-length molecular clones of RT from serum-derived viruses were amplified at each of 12 consecutive time points.

RESULTS: In the 3.5-year period prior to the first course of therapy, only wt viruses were present. As soon as 6 months after the start of AZT monotherapy, all viruses contained the insertion and aa changes at positions 67 and 215, a combination conferring resistance to AZT, d4T, 3TC, ddI, and ddC. After termination of therapy, the insertion mutants were rapidly and completely replaced by the wt viruses. In turn, the insertion mutants replaced the wt viruses after initiation of therapy with 3TC, d4T, and SQV. After termination of triple therapy, the wt viruses replaced the insertion mutants completely within one month. Based on the dynamics of replacements of virus populations in relation to availability of therapy, the relative fitness of the insertion mutant was estimated to be 37% lower in a drug-free competitive environment and 55% higher in a drug-loaded noncompetitive environment.

CONCLUSIONS: The insertion mutants do arise and may be selected during AZT monotherapy. Despite their competitive disadvantage, the insertion mutants maintained high virus loads (up to 100000 per ml) in the presence of drugs and CD4+ cell counts >50/ul.

Keywords: AEGIS, Zidovudine, HIV-1, Stavudine, HIV-1 Reverse Transcriptase, Didanosine, Lamivudine, Zalcitabine, Pharmaceutical PreparationsKWDaegis,zidovudine,hiv-1,stavudine,hiv-1reversetranscriptase,didanosine,lamivudine,zalcitabine,pharmaceuticalpreparations
000709
TuOrA351

Copyright © 2000 - International AIDS Society (IAS). Reproduction of this abstract (other than one copy for personal reference) must be cleared through the IAS.