Naturally occurring resistance mutations to HIV-1 entry inhibitors in subtypes B, C, and CRF31_BC

详细信息	查看全文 | 推荐本文 |

• 作者：Leonardo Augusto Luvison Ara&uacute ; jo^a ; ^{leonardo_luvison@hotmail.com} ; Dennis Maletich Junqueira^a ; ^b ; Rubia Mar&iacute ; lia de Medeiros^a ; ^b ; Maria Cristina Cotta Matte^a ; ^b ; Sabrina Esteves de Matos Almeida^a
• 关键词：ARV ; antiretroviral ; FDA ; Food and Drug Administration ; ENF ; Enfuvirtide ; MVC ; Maraviroc ; VCV ; Vicriviroc ; HR1 ; first heptad repeat region ; HR2 ; second heptad repeat region ; pol ; polimerase ; env ; envelope ; CRF ; circulating recombinant form ; URF ; unique re
• 刊名：Journal of Clinical Virology
• 出版年：2012
• 期刊代码：150_13866532
• 类别：med
• 出版时间：May, 2012
• 卷：54
• 期：1
• 页码：6-10
• 文件大小：258 K

摘要

class="h4">Background

Entry inhibitors are a class of antiretroviral (ARV) drugs that prevent HIV replication by blocking viral entry into the host cell. The investigation of naturally occurring mutations associated with entry inhibitors across subtypes is required because genetic differences between HIV-1 variants may influence the emergence of drug resistance. Despite the importance of subtype C, which predominates globally, the majority of studies include only subtype B strains.

class="h4">Objectives

To investigate the presence of natural resistance mutations to entry inhibitors in HIV-1 subtypes B, C, and CRF31_BC strains.

class="h4">Study design

Eighty samples were collected from antiretroviral-na茂ve patients. The gp41 gene from 67 patients and the gp120 gene from 65 patients were partially sequenced. Resistance mutations to entry inhibitors Enfuvirtide, Maraviroc, and Vicriviroc were screened.

class="h4">Results

ENF resistance-associated mutations of HR1 and HR2 on gp41 were not associated with any subtype. However, the major polymorphisms detected in HR1: N42S, L54M, and A67T were most prevalent in subtype C (p < 0.001). Mutations A316T and R315Q in gp120, which are related to MVC and VCV reduced susceptibility respectively, were predominant in subtype C (p < 0.05).

class="h4">Conclusions

This study shows that many more resistance-associated mutations to entry inhibitors in ARV-na茂ve patients occur in subtype C compared with subtype B strains. However, further studies will be necessary to elucidate if the differential genetic background of HIV subtypes can affect the efficacy of treatment with entry inhibitors.