Department of Pharmacology and Experimental Neuroscience, College of Medicine, University of Nebraska Medical Center, Omaha, NE, USA.
Virology Laboratory, Chantal BIYA International Reference Centre for research on HIV/AIDS prevention and management, Yaoundé, Cameroon.
Sci Rep. 2017 Oct 26;7(1):14136. doi: 10.1038/s41598-017-14095-4.
In HIV-1 subtype-B, specific mutations in Gag cleavage sites (CS) are associated with treatment failure, with limited knowledge among non-B subtypes. We analyzed non-B HIV-1 gag and pol (protease/reverse-transcriptase) sequences from Cameroonians for drug resistance mutations (DRMs) in the gag P2/NC CS, and pol major DRMs. Phylogeny of the 141 sequences revealed a high genetic diversity (12 subtypes): 67.37% CRF02_AG versus 32.6% non-CRF02_AG. Overall, 7.3% transmitted and 34.3% acquired DRMs were found, including M184V, thymidine analogue mutations (T215F, D67N, K70R, K219Q), NNRTIs (L100I, Y181C, K103N, V108I, Y188L), and PIs (V82L). Twelve subjects [10 with HIV-1 CRF02_AG, 8 treatment-naïve and 4 on 3TC-AZT-NVP] showed 3 to 4 mutations in the Gag P2/NC CS: S373Q/T/A, A374T/S/G/N, T375S/A/N/G, I376V, G381S, and R380K. Subjects with or without Gag P2/NC CS mutations showed no significant difference in viral loads. Treatment-naïve subjects harboring NRTI-DRMs had significantly lower CD4 cells than those with NRTI-DRMs on ART (p = 0.042). Interestingly, two subjects had major DRMs to NRTIs, NNRTIs, and 4 mutations in the Gag P2/NC CS. In this prevailing CRF02_AG population with little exposure to PIs (~3%), mutations in the Gag P2/NC CS could increase the risk of treatment failure if there is increased use of PIs-based therapy.
在 HIV-1 亚型 B 中，Gag 切割位点（CS）的特定突变与治疗失败相关，但在非 B 亚型中知之甚少。我们分析了来自喀麦隆人的非 B HIV-1 gag 和 pol（蛋白酶/逆转录酶）序列，以研究 gag P2/NC CS 和 pol 主要耐药突变（DRMs）中的耐药突变（DRMs）。141 条序列的系统发育显示出高度的遗传多样性（12 种亚型）：67.37%为 CRF02_AG，32.6%为非 CRF02_AG。总体而言，发现了 7.3%的传播和 34.3%的获得性 DRMs，包括 M184V、胸苷类似物突变（T215F、D67N、K70R、K219Q）、NNRTIs（L100I、Y181C、K103N、V108I、Y188L）和 PIs（V82L）。12 名受试者[10 名携带 HIV-1 CRF02_AG，8 名未接受治疗，4 名接受 3TC-AZT-NVP 治疗]在 gag P2/NC CS 中显示 3 到 4 种突变：S373Q/T/A、A374T/S/G/N、T375S/A/N/G、I376V、G381S 和 R380K。携带或不携带 gag P2/NC CS 突变的受试者的病毒载量没有显著差异。携带 NRTI-DRMs 的未接受治疗的受试者的 CD4 细胞明显低于接受 ART 治疗的携带 NRTI-DRMs 的受试者（p=0.042）。有趣的是，两名受试者对 NRTIs、NNRTIs 和 gag P2/NC CS 的 4 种突变具有主要的 DRMs。在这种流行的主要为 CRF02_AG 人群中，很少接触到 PIs（~3%），如果增加使用基于 PIs 的治疗，Gag P2/NC CS 中的突变可能会增加治疗失败的风险。
