Kalu Amare Worku, Telele Nigus Fikrie, Gebreselasie Solomon, Fekade Daniel, Abdurahman Samir, Marrone Gaetano, Sönnerborg Anders
Division of Clinical Microbiology, Department of Laboratory Medicine, Karolinska Institute, Alfred Nobels Alle 8, F68, Huddinge, Stockholm, 14186, Sweden.
Department of Microbiology, Immunology and Parasitology, Addis Ababa University, Addis Ababa, Ethiopia.
BMC Infect Dis. 2017 Jan 6;17(1):37. doi: 10.1186/s12879-016-2163-1.
CCR5 coreceptor using HIV-1 subtype C (HIV-1C) has been reported to dominate the Ethiopian epidemic. However, almost all data have been obtained from two large cities in the central and north-west regions and recent data is lacking.
Plasma were obtained from 420 treatment-naïve patients recruited 2009-2011 to a large country-wide Ethiopian cohort. The V3 region was sequenced and the co-receptor tropism was predicted by the clinical and clonal models of the geno2pheno tool at different false positive rates (fpr) and for subtype. In an intention to treat analysis the impact of baseline tropism on outcome of antiretroviral therapy was evaluated.
V3 loop sequencing was successful in 352 (84%) patients. HIV-1C was found in 350 (99.4%) and HIV-1A in two (0.6%) patients. When comparing the geno2pheno fpr10% clonal and clinical models, 24.4% predictions were discordant. X4-virus was predicted in 17.0 and 19.0%, respectively, but the predictions were concordant in only 6%. At fpr5%, concordant X4-virus predictions were obtained in 3.1%. The proportion of X4-tropic virus (clonal fpr10%) increased from 5.6 to 17.3% (p < 0.001) when 387 Ethiopian V3 loop sequences dated from 1984 to 2003 were compared with ours. In an intention to treat analysis, 67.9% reached treatment success at month 6 and only 50% at month 12. Only age and not tropism predicted therapy outcome and no difference was found in CD4+ cell gain between R5-tropic and X4-tropic infected patients. At viral failure, R5 to X4 switch was rare while X4 to R5 switch occurred more frequently (month 6: p = 0.006; month 12: p = 0.078).
The HIV-1C epidemic is monophylogenetic in all regions of Ethiopia and R5-tropic virus dominates, even in patients with advanced immunodeficiency, although the proportion of X4-tropic virus seems to have increased over the last two decades. Geno2pheno clinical and clonal prediction models show a large discrepancy at fpr10%, but not at fpr5%. Hence further studies are needed to assess the utility of genotypic tropism testing in HIV-1C. In ITT analysis only age and not tropism influenced the outcome.
据报道，使用CCR5共受体的HIV-1 C亚型（HIV-1C）在埃塞俄比亚的艾滋病流行中占主导地位。然而，几乎所有数据均来自中部和西北部地区的两个大城市，且缺乏近期数据。
从2009年至2011年招募到埃塞俄比亚一个大型全国队列中的420例未经治疗的患者获取血浆。对V3区进行测序，并通过geno2pheno工具的临床和克隆模型在不同假阳性率（fpr）下预测共受体嗜性及亚型。在一项意向性分析中，评估基线嗜性对抗逆转录病毒治疗结果的影响。
352例（84%）患者的V3环测序成功。350例（99.4%）患者检测到HIV-1C，2例（0.6%）患者检测到HIV-1A。比较geno2pheno fpr10%的克隆模型和临床模型时，24.4%的预测结果不一致。分别有17.0%和19.0%的患者预测为X4病毒，但仅6%的预测结果一致。在fpr5%时，X4病毒预测结果的一致性为3.1%。将1984年至2003年的387条埃塞俄比亚V3环序列与我们的数据进行比较时，X4嗜性病毒的比例（克隆fpr10%）从5.6%增至17.3%（p<0.001）。在意向性分析中，67.9%的患者在第6个月治疗成功，第12个月时仅为50%。仅年龄而非嗜性可预测治疗结果，R5嗜性和X4嗜性感染患者的CD4 +细胞增加无差异。在病毒学失败时，R5向X4转换少见，而X4向R5转换更频繁（第6个月：p = 0.006；第12个月：p = 0.078）。
埃塞俄比亚所有地区的HIV-1C流行均为单系发生，R5嗜性病毒占主导地位，即使在免疫缺陷严重的患者中也是如此，尽管在过去二十年中X4嗜性病毒的比例似乎有所增加。geno2pheno临床和克隆预测模型在fpr10%时差异较大，但在fpr5%时并非如此。因此，需要进一步研究以评估HIV-1C基因嗜性检测的实用性。在意向性分析中，仅年龄而非嗜性影响治疗结果。
