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09 September 2002

Resistance mutations in HIV-infected patients experiencing early failure with nelfinavir-containing triple combinations

Marina Núńez, Carmen de Mendoza, Luisa Valer, Esperanza Casas, Soledad López-Calvo, Ángeles Castro, Beatriz Rosón, Daniel Podzamczer, Amalia Rubio, Juan Berenguer, Vincent Soriano

Med Sci Monit 2002; 8(9): CR620-623 :: ID: 13277

Abstract

Summary
Background: The purpose of our study was to assess the presence of nelfinavir (NFV)-associated resistance mutations at the time of early virological failure in subjects receiving NFV as part of a first protease inhibitor (PI)-based triple regimen.
Material/Methods: Subjects failing their first PI-based NFV-containing triple regimen were identified in six Spanish hospitals. HIV genotyping was carried out in plasma samples collected at the time of
the first viral rebound.
Results: Upon initiation of NFV-based therapy, 19 of the 30 subjects (63%) were naïve; 11 (37%) had been exposed to nucleoside analogues. Median HIV-RNA at the time of viral rebound was 4,
180 copies/ml. PCR-amplified products were obtained in 22 subjects (73%). These products were sequenced and primary PI resistance mutations were recognized in 6 patients (27%). All six individuals harbored the D30N mutation, and none presented the L90M mutation. Other PI resistance mutations were present in 5 subjects (at codons 36, 63, 71, 77, 82 and/or 88). Secondary PI resistance mutations were present in another 9 subjects. By contrast, mutations conferring resistance to reverse transcriptase inhibitors were present in 50% of the patients, and the M184V substitution was the most frequently seen.
Conclusions: Nearly 75% of patients failing their first PI-based triple regimen containing NFV do not harbor PI resistance mutations. The D30N substitution, rather than L90M, is the most frequently
recognized, which does not challenge the efficacy of further rescue interventions with other PIs. This observation supports the use of nelfinavir as first protease inhibitor

Keywords: Drug Resistance, Genes, Viral, Genotype, HIV - genetics, HIV Protease - genetics, HIV Protease Inhibitors - therapeutic use, HIV Seropositivity - drug therapy, HIV-1 Reverse Transcriptase - genetics, Mutation, Nelfinavir - therapeutic use

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