加蓬利伯维尔接受二线抗逆转录病毒治疗的患者中的 HIV 蛋白酶耐药突变。

HIV protease resistance mutations in patients receiving second-line antiretroviral therapy in Libreville, Gabon.

机构信息

Département de Bactériologie- Virologie, Laboratoire National de Référence IST/VIH/Sida, Université des Sciences de la Santé, Libreville, Gabon.

出版信息

BMC Infect Dis. 2024 Mar 14;24(1):316. doi: 10.1186/s12879-024-09156-9.

DOI:10.1186/s12879-024-09156-9

PMID:38486188

原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC10941465/

Abstract

INTRODUCTION

In 2022, the WHO reported that 29.8 million people around the world were living with HIV (PLHIV) and receiving antiretroviral treatment (ART), including 25‌ 375 people in Gabon (54% of all those living with HIV in the country). The literature reports a frequency of therapeutic failure with first-line antiretrovirals (ARVs) of between 20% and 82%. Unfortunately, data relating to the failure of second-line ARVs are scarce in Gabon. This study aims to determine the profiles of HIV drug resistance mutations related to protease inhibitors in Gabon.

METHODOLOGY

Plasma from 84 PLHIV receiving ARVs was collected from 2019 to 2021, followed by RNA extraction, amplification, and sequencing of the protease gene. ARV resistance profiles were generated using the Stanford interpretation algorithm version 8.9-1 ( https://hivdb.stanford.edu ) and statistical analyses were performed using EpiInfo software version 7.2.1.0 (CDC, USA).

RESULTS

Of 84 HIV plasma samples collected from 45 men and 39 women, 342 mutations were detected. Of these, 43.3% (148/342) were associated with nucleoside reverse transcriptase inhibitors (NRTIs), 30.4% (104/342) with non-nucleoside reverse transcriptase inhibitors (NNRTIs), and 26.3% (90/342) with protease inhibitors (PIs). Most NRTI mutations were associated with thymidine analogues (TAMs) (50.7%; 75/148), including T215F/V (14.9%; 22/148), D67DN/E/G/N/T (10.1%; 15/148), M41L (9.5%; 14/148), and K70E/KN/S/R (9.5%; 14/148). Resistance mutations related to non-TAM NRTIs (33.1%; 49/148) were M184V (29.1%; 43/148), and L74I/V (8.1%; 12/148). NNRTI mutations were predominantly K103N/S (32.7%; 34/104), V108I (10.6%; 11/104), A98G (10.6%; 11/104), and P225H (9.6%; 10/104). Minor mutations associated with PIs (60.0%; 54/90) were predominantly K20I (15.6%; 14/90) and L10F/I/V (14.5%; 13/90). The major mutations associated with PIs (40.0%; 36/90) were M41L (12.2%; 11/90), I84V (6.7%; 06/90), and V82A (6.7%; 06/90). The four most prescribed therapeutic regimens were TDF + 3TC + LPV/r (20.3%; 17/84), ABC + DDI + LPV/r (17.9%; 15/84), TDF + FTC + LPV/r (11.9%; 10/84), and ABC + 3TC + LPV/r (11.9%; 10/84).

CONCLUSION

This study revealed that HIV drug resistance mutations are common in Gabon. The major mutations associated with PIs were M41L, I84V, and V82A. There is a need for access to new NRTIs, NNRTIs, and PIs for a better therapeutic management of PLHIV in Gabon.

摘要

简介

2022 年，世界卫生组织报告称，全球有 2980 万人（PLHIV）携带艾滋病毒并接受抗逆转录病毒治疗（ART），其中包括加蓬的 25375 人（占该国所有携带艾滋病毒者的 54%）。文献报道，一线抗逆转录病毒药物（ARVs）的治疗失败频率在 20%至 82%之间。不幸的是，有关加蓬二线 ARV 治疗失败的数据很少。本研究旨在确定与蛋白酶抑制剂相关的 HIV 耐药突变体在加蓬的情况。

方法

从 2019 年至 2021 年，采集了 84 名接受 ARV 治疗的 PLHIV 的血浆，随后提取 RNA、扩增和测序蛋白酶基因。使用斯坦福解释算法版本 8.9-1（https://hivdb.stanford.edu）生成 ARV 耐药谱，并使用 EpiInfo 软件版本 7.2.1.0（CDC，美国）进行统计分析。

结果

从 45 名男性和 39 名女性中采集了 84 份 HIV 血浆样本，共检测到 342 个突变。其中，43.3%（148/342）与核苷逆转录酶抑制剂（NRTIs）相关，30.4%（104/342）与非核苷逆转录酶抑制剂（NNRTIs）相关，26.3%（90/342）与蛋白酶抑制剂（PIs）相关。大多数 NRTI 突变与胸苷类似物（TAMs）相关（50.7%；75/148），包括 T215F/V（14.9%；22/148）、D67DN/EGNT（10.1%；15/148）、M41L（9.5%；14/148）和 K70E/KN/S/R（9.5%；14/148）。与非 TAM NRTIs 相关的耐药突变（33.1%；49/148）为 M184V（29.1%；43/148）和 L74I/V（8.1%；12/148）。NNRTI 突变主要为 K103N/S（32.7%；34/104）、V108I（10.6%；11/104）、A98G（10.6%；11/104）和 P225H（9.6%；10/104）。与 PIs 相关的次要突变（60.0%；54/90）主要为 K20I（15.6%；14/90）和 L10F/I/V（14.5%；13/90）。与 PIs 相关的主要突变（40.0%；36/90）为 M41L（12.2%；11/90）、I84V（6.7%；06/90）和 V82A（6.7%；06/90）。最常开的四种治疗方案为 TDF+3TC+LPV/r（20.3%；17/84）、ABC+DDI+LPV/r（17.9%；15/84）、TDF+FTC+LPV/r（11.9%；10/84）和 ABC+3TC+LPV/r（11.9%；10/84）。