Onywera Harris, Maman David, Inzaule Seth, Auma Erick, Were Kennedy, Fredrick Harrison, Owiti Prestone, Opollo Valarie, Etard Jean-François, Mukui Irene, Kim Andrea A, Zeh Clement
Center for Global Health Research (CGHR), Kenya Medical Research Institute (KEMRI), Kisumu, Kenya.
Epicentre, Médecins Sans Frontières (MSF), Paris, France.
PLoS One. 2017 Feb 8;12(2):e0171124. doi: 10.1371/journal.pone.0171124. eCollection 2017.
HIV-1 transmitted drug resistance (TDR) is of increasing public health concern in sub-Saharan Africa with the rollout of antiretroviral (ARV) therapy. Such data are, however, limited in Kenya, where HIV-1 drug resistance testing is not routinely performed. From a population-based household survey conducted between September and November 2012 in rural western Kenya, we retrospectively assessed HIV-1 TDR baseline rates, its determinants, and genetic diversity among drug-naïve persons aged 15-59 years with acute HIV-1 infections (AHI) and recent HIV-1 infections (RHI) as determined by nucleic acid amplification test and both Limiting Antigen and BioRad avidity immunoassays, respectively. HIV-1 pol sequences were scored for drug resistance mutations using Stanford HIVdb and WHO 2009 mutation guidelines. HIV-1 subtyping was computed in MEGA6. Eighty seven (93.5%) of the eligible samples were successfully sequenced. Of these, 8 had at least one TDR mutation, resulting in a TDR prevalence of 9.2% (95% CI 4.7-17.1). No TDR was observed among persons with AHI (n = 7). TDR prevalence was 4.6% (95% CI 1.8-11.2) for nucleoside reverse transcriptase inhibitors (NRTIs), 6.9% (95% CI 3.2-14.2) for non- nucleoside reverse transcriptase inhibitors (NNRTIs), and 1.2% (95% CI 0.2-6.2) for protease inhibitors. Three (3.4% 95% CI 0.8-10.1) persons had dual-class NRTI/NNRTI resistance. Predominant TDR mutations in the reverse transcriptase included K103N/S (4.6%) and M184V (2.3%); only M46I/L (1.1%) occurred in the protease. All the eight persons were predicted to have different grades of resistance to the ARV regimens, ranging from potential low-level to high-level resistance. HIV-1 subtype distribution was heterogeneous: A (57.5%), C (6.9%), D (21.8%), G (2.3%), and circulating recombinant forms (11.5%). Only low CD4 count was associated with TDR (p = 0.0145). Our findings warrant the need for enhanced HIV-1 TDR monitoring in order to inform on population-based therapeutic guidelines and public health interventions.
随着抗逆转录病毒（ARV）疗法在撒哈拉以南非洲地区的推广，HIV-1传播性耐药（TDR）日益引起公共卫生领域的关注。然而，在肯尼亚，此类数据有限，该国并未常规开展HIV-1耐药性检测。我们从2012年9月至11月在肯尼亚西部农村地区开展的一项基于人群的家庭调查中，对15至59岁未接受过治疗、经核酸扩增检测确诊为急性HIV-1感染（AHI）以及经限量抗原和伯乐亲和力免疫测定确诊为近期HIV-1感染（RHI）的人群，回顾性评估了HIV-1 TDR基线率、其决定因素以及基因多样性。使用斯坦福HIV数据库和世界卫生组织2009年突变指南对HIV-1 pol序列进行耐药性突变评分。在MEGA6中进行HIV-1亚型分析。87份（93.5%）符合条件的样本成功测序。其中，8份样本至少有一个TDR突变，TDR患病率为9.2%（95%置信区间4.7 - 17.1）。在AHI患者（n = 7）中未观察到TDR。核苷类逆转录酶抑制剂（NRTIs）的TDR患病率为4.6%（95%置信区间1.8 - 11.2），非核苷类逆转录酶抑制剂（NNRTIs）为6.9%（95%置信区间3.2 - 14.2），蛋白酶抑制剂为1.2%（95%置信区间0.2 - 6.2）。3人（3.4%，95%置信区间0.8 - 10.1）存在NRTI/NNRTI双重耐药。逆转录酶中的主要TDR突变包括K103N/S（4.6%）和M184V（2.3%）；蛋白酶中仅出现M46I/L（1.1%）。预计所有8人均对ARV治疗方案具有不同程度的耐药性，从潜在的低水平耐药到高水平耐药。HIV-1亚型分布不均：A（57.5%）、C（6.9%）、D（21.8%）、G（2.3%）以及循环重组型（11.5%）。仅低CD4细胞计数与TDR相关（p = 0.0145）。我们的研究结果表明有必要加强HIV-1 TDR监测，以便为基于人群的治疗指南和公共卫生干预提供依据。
