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Multicenter Study
. 2000 Aug;44(8):2109-17.
doi: 10.1128/aac.44.8.2109-2117.2000.

Prevalence and Characteristics of Multinucleoside-Resistant Human Immunodeficiency Virus Type 1 Among European Patients Receiving Combinations of Nucleoside Analogues

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Free PMC article
Multicenter Study

Prevalence and Characteristics of Multinucleoside-Resistant Human Immunodeficiency Virus Type 1 Among European Patients Receiving Combinations of Nucleoside Analogues

K Van Vaerenbergh et al. Antimicrob Agents Chemother. .
Free PMC article

Abstract

The prevalence and the genotypic and phenotypic characteristics of multinucleoside-resistant (MNR) human immunodeficiency virus type 1 (HIV-1) variants in Europe were investigated in a multicenter study that involved centers in nine European countries. Study samples (n = 363) collected between 1991 and 1997 from patients exposed to two or more nucleoside analogue reverse transcriptase inhibitors (NRTIs) and 274 control samples from patients exposed to no or one NRTI were screened for two marker mutations of multinucleoside resistance (the Q151M mutation and a mutation with a 2-amino-acid insertion at codon 69, T69S-XX). Q151M was identified in six of the study samples (1. 6%), and T69S-XX was identified in two of the study samples (0.5%; both of them T69S-SS), but both patterns were absent among control samples. Non-NRTI (NNRTI)-related changes were observed in viral strains from two patients, which displayed the Q151M resistance pattern, although the patients were NNRTI naive. The patients whose isolates displayed multinucleoside resistance had received treatment with zidovudine and either didanosine, zalcitabine, or stavudine. Both resistance patterns conferred broad cross-resistance to NRTIs in vitro and a poor response to treatment in vivo. MNR HIV-1 is found only among multinucleoside-experienced patients. Its prevalence is low in Europe, but it should be closely monitored since it seriously limits treatment options.

Figures

FIG. 1
FIG. 1
Evolution of CD4-cell count (number of cells per microliter), viral load (log10 number of copies of RNA per milliliter) and resistance-related genotype of the RT gene for patients SW3 (A) and CHG (B) who harbored viruses with the T69S-SS mutation. The times of retrieval of the original samples included in the screening, SW3-10125 and CHG-4815, respectively, are indicated by the bold arrow. Patient CHG had been treated with zidovudine (ZDV) since December 1990. ddI, didanosine; 3TC, lamivudine; d4T, stavudine; IDV, indinavir; WT, wild type.

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