Department of Immunology & Infectious Diseases, Harvard T. H. Chan School of Public Health, Boston, MA, USA.
Department of Haematology and Blood Transfusion, College of Medicine of the University of Lagos, Lagos, Nigeria.
J Antimicrob Chemother. 2019 Jan 1;74(1):172-176. doi: 10.1093/jac/dky380.
Many lines of evidence point to HIV-1 subtype-specific differences in the development of drug resistance mutations. While variation between subtype C and others has been extensively explored, there has been less emphasis on subtypes common to West Africa. We examined a previously described national survey of pretreatment drug resistance in HIV-1-infected Nigerian children aged <18 months, to explore the association between subtypes and patterns of resistance.
Five hundred and forty-nine dried blood spots, from 15 early infant diagnostic facilities in Nigeria, were amplified and HIV-1 polymerase was sequenced. Four hundred and twenty-four were analysed for surveillance drug resistance mutations (SDRMs). Associations between subtype and SDRMs were evaluated by Fisher's exact test and logistic regression analysis, controlling for geographical region and exposure.
Using the sub-subtypes of HIV-1 G defined by Delatorre et al. (PLoS One 2014.
9: e98908) the most common subtypes were CRF02_AG (174, 41.0%), GWA-I (128, 30.2%), GWA-II (24, 5.7%), GCA (11, 2.6%), A (21, 5.0%) and CRF06_cpx (18, 4.2%). One hundred and ninety infants (44.8%) had ≥1 NNRTI mutation, 92 infants (21.7%) had ≥1 NRTI mutation and 6 infants (1.4%) had ≥1 PI mutation. By logistic regression, 67N was more common in GWA-II/GCA than CRF02_AG (OR 12.0, P = 0.006), as was 70R (OR 23.1, P = 0.007), 184I/V (OR 2.92, P = 0.020), the presence of ≥1 thymidine analogue mutation (TAM) (OR 3.87, P = 0.014), ≥1 type 2 TAM (OR 7.61, P = 0.001) and ≥1 NRTI mutation (OR 3.26, P = 0.005).
This dataset reveals differences among SDRMs by subtype; in particular, between the GWA-II and GCA subclades, compared with CRF02_AG and GWA-I.
大量证据表明，HIV-1 亚型特异性差异会导致耐药突变的发展。虽然已经广泛研究了 C 型与其他亚型之间的变异，但对西非常见亚型的关注较少。我们研究了之前描述的尼日利亚 18 个月以下感染 HIV-1 的儿童治疗前耐药的全国性调查，以探讨亚型与耐药模式之间的关系。
从尼日利亚 15 个早期婴儿诊断机构采集了 549 个干血斑，扩增了 HIV-1 聚合酶并进行了测序。对 424 个样本进行了监测耐药突变（SDRMs）分析。通过 Fisher 精确检验和逻辑回归分析评估了亚型与 SDRMs 之间的关联，控制了地理位置和暴露因素。
使用 Delatorre 等人定义的 HIV-1 G 的亚亚型（PLoS One 2014.
9: e98908），最常见的亚型是 CRF02_AG（174，41.0%）、GWA-I（128，30.2%）、GWA-II（24，5.7%）、GCA（11，2.6%）、A（21，5.0%）和 CRF06_cpx（18，4.2%）。190 名婴儿（44.8%）有≥1 种 NNRTI 突变，92 名婴儿（21.7%）有≥1 种 NRTI 突变，6 名婴儿（1.4%）有≥1 种 PI 突变。通过逻辑回归，67N 在 GWA-II/GCA 中比 CRF02_AG 更常见（OR 12.0，P=0.006），70R（OR 23.1，P=0.007）、184I/V（OR 2.92，P=0.020）、存在≥1 种胸苷类似物突变（TAM）（OR 3.87，P=0.014）、≥1 种 2 型 TAM（OR 7.61，P=0.001）和≥1 种 NRTI 突变（OR 3.26，P=0.005）也更常见。
该数据集揭示了不同亚型之间 SDRMs 的差异；特别是在 GWA-II 和 GCA 亚群之间，与 CRF02_AG 和 GWA-I 相比。
