Department of Microbiology and Parasitology, University of Buea, Buea, SW Region, Cameroon.
BioCollections Worldwide Inc., Regional Office, Buea, SW Region, Cameroon.
PLoS One. 2019 Nov 21;14(11):e0225575. doi: 10.1371/journal.pone.0225575. eCollection 2019.
Antiretroviral therapy (ART) has improved the survival of HIV infected persons. However, rapid scale-up of ART and the high HIV-1 genetic variability, has greatly influenced the emergence of drug-resistant strains. This constitutes a potential threat to achieving the UNAIDS' 90-90-90 goals by 2020. We investigated the prevalent HIV-1 genotypes, drug resistance-associated mutations and assessed some predictors of the occurrence of these mutations.
This was a hospital-based cross-sectional study conducted between October 2010 and June 2012. Participants were consecutively enrolled from selected HIV treatment centers of the Southwest and Northwest regions of Cameroon. Viral load was determined with the automated Abbott Real-time HIV-1 m2000rt System. HIV genotyping and antiretroviral resistance mutations analysis were performed using Bayer's HIV-1 TRUGENE™ Genotyping Kit and OpenGene DNA Sequencing system. The drug resistance mutation was interpreted with the Stanford HIV database. Epidemiological data were obtained using pre-tested semi-structured questionnaires.
Of the 387 participants, 239 were successfully genotyped. The median age of these participants was 33 years (interquartile range, IQR: 28-40 years), and a majority (65.7%) were female. A total of 29.3% of the participants were receiving ART. The median duration of ART was 10.5 months (IQR: 4-17.25 months). The median CD4 count and log10 viral load of study participants were 353.5 cells/ml (IQR:145-471) and 4.89 copies/ml (IQR: 3.91-5.55) respectively. CRF02 (A/G) (69%) was the most prevalent subtype followed by G (8.2%) and F (6.7%). Overall, resistance mutations were present in 37.1% of ART-experienced and 10.7% of ART-naive patients. Nucleoside reverse transcriptase inhibitors (NRTI) mutations occurred in 30% of ART-experienced and 2.4% of ART-naïve patients, while non-nucleoside reverse transcriptase inhibitors (NNRTI) mutations occurred in 34.2% of ART-experienced and 10.1% of -naïve patients. M184V (8.4%, 20/239) and K103N (5.4%, 13/239) were the most prevalent mutations. Major protease inhibitor mutations occurred in 3 (1.3%) out of the 239 sequences. The duration of ART independently predicted the occurrence of resistance mutation among ART-experienced patients.
The high resistance to NNRTIs, which are the main support to the backbone (NRTIs) first-line antiretroviral regimen in Cameroon, has prompted the need to rollout an integrase strand transfer inhibitor regimen (containing Dolutegravir) with a higher genetic barrier to resistance as the preferred first line regimen.
抗逆转录病毒疗法（ART）改善了 HIV 感染者的生存状况。然而，ART 的快速推广以及 HIV-1 高度的遗传变异性，极大地影响了耐药菌株的出现。这对 2020 年实现联合国艾滋病规划署的 90-90-90 目标构成了潜在威胁。我们调查了 HIV-1 基因型、耐药相关突变的流行情况，并评估了这些突变发生的一些预测因素。
这是一项在 2010 年 10 月至 2012 年 6 月期间进行的基于医院的横断面研究。参与者是从喀麦隆西南部和西北部选定的 HIV 治疗中心连续招募的。采用自动 Abbott Real-time HIV-1 m2000rt 系统测定病毒载量。使用 Bayer 的 HIV-1 TRUGENE™ Genotyping Kit 和 OpenGene DNA Sequencing system 进行 HIV 基因分型和抗逆转录病毒耐药性突变分析。耐药突变的解释采用斯坦福 HIV 数据库。通过预先测试的半结构式问卷获得流行病学数据。
在 387 名参与者中，有 239 名成功进行了基因分型。这些参与者的中位年龄为 33 岁（四分位间距 IQR：28-40 岁），大多数（65.7%）为女性。共有 29.3%的参与者正在接受 ART。ART 的中位持续时间为 10.5 个月（IQR：4-17.25 个月）。研究参与者的中位 CD4 计数和 log10 病毒载量分别为 353.5 个细胞/ml（IQR：145-471）和 4.89 拷贝/ml（IQR：3.91-5.55）。最常见的亚型是 CRF02（A/G）（69%），其次是 G（8.2%）和 F（6.7%）。总体而言，耐药突变在 37.1%的 ART 经验患者和 10.7%的 ART 初治患者中存在。核苷类逆转录酶抑制剂（NRTI）突变发生在 30%的 ART 经验患者和 2.4%的 ART 初治患者中，而非核苷类逆转录酶抑制剂（NNRTI）突变发生在 34.2%的 ART 经验患者和 10.1%的 ART 初治患者中。M184V（8.4%，20/239）和 K103N（5.4%，13/239）是最常见的突变。主要蛋白酶抑制剂突变发生在 239 个序列中的 3 个（1.3%）。ART 经验患者中，ART 持续时间是耐药突变发生的独立预测因素。
对 NNRTIs 的高度耐药性，这是喀麦隆一线抗逆转录病毒方案（NRTIs）的主要支持，促使需要推出一种具有更高遗传耐药屏障的整合酶链转移抑制剂方案（包含多替拉韦）作为首选一线方案。
