Tebit Denis M, Sangaré Lassana, Tiba Fabrice, Saydou Yameogo, Makamtse Aline, Somlare Hermann, Bado Guillaume, Kouldiaty Boris G, Zabsonre Inoussa, Yameogo Sibiri L, Sathiandee Kanokporn, Drabo Joseph Y, Kräusslich Hans-Georg
Abteilung Virologie, Universitaetsklinikum Heidelberg, Heidelberg, Germany.
J Med Virol. 2009 Oct;81(10):1691-701. doi: 10.1002/jmv.21600.
A cross-sectional study was undertaken among drug-naïve HIV patients at the University Hospital in Ouagadougou shortly before and after the introduction of large-scale antiretroviral therapy (ART) in Burkina Faso. Baseline clinical and virological data as well as protease (PR) and 5' reverse transcriptase (RT) sequences from 104 HIV infected patients were analyzed. Genotypic classification revealed the following subtypes and recombinant forms: CRF06_cpx, n = 46 (44.2%); CRF02_AG, n = 39 (37.5%); subtype A, n = 4 (3.8%); CRF09_cpx, n = 2 (1.9%); and unclassified, n = 13 (12.5%). Bootstrap analysis of CRF02_AG and CRF06_cpx viruses showed that >80% had a similar structure to their respective prototypes. The prevalence of primary drug resistance mutations was 12.5%, all mutations arising in the RT sequences in accordance with the dominance of this drug class in Burkina Faso. The mutations were distributed as follows: NRTI (10.6%): M41L (n = 2), D67N (n = 2), K70K/E (n = 2), L210W (n = 1), T215S/Y (n = 2), and K219K/Q (n = 2); NNRTI (6.1%): K103K/N (n = 2), Y181C (n = 2), G190G/A (n = 1), and P236P/L (n = 1). Subtype specific secondary polymorphisms such as K20I and M36I in the PR were observed in almost all patients. Drug resistance mutations occurred at similar frequencies (12.8% and 10.8%, respectively) among patients infected with CRF02_AG and CRF06_cpx. Some subtype specific polymorphisms were observed within important HLA epitopes, including B35, B7, and A2 in the RT, and A*6802 in the PR sequences. The observed resistance mutations are most likely to have been transmitted based on the timing of the study but prior undocumented use of ART cannot be excluded.
在布基纳法索大规模引入抗逆转录病毒疗法（ART）之前和之后不久，对瓦加杜古大学医院未接受过治疗的HIV患者进行了一项横断面研究。分析了104例HIV感染患者的基线临床和病毒学数据以及蛋白酶（PR）和5'逆转录酶（RT）序列。基因分型显示了以下亚型和重组形式：CRF06_cpx，n = 46（44.2%）；CRF02_AG，n = 39（37.5%）；A亚型，n = 4（3.8%）；CRF09_cpx，n = 2（1.9%）；未分类，n = 13（12.5%）。对CRF02_AG和CRF06_cpx病毒的自展分析表明，>80%的病毒与各自的原型具有相似的结构。原发性耐药突变的发生率为12.5%，所有突变均出现在RT序列中，这与该药物类别在布基纳法索的主导地位一致。突变分布如下：核苷类逆转录酶抑制剂（NRTI）（10.6%）：M41L（n = 2）、D67N（n = 2）、K70K/E（n = 2）、L210W（n = 1）、T215S/Y（n = 2）和K219K/Q（n = 2）；非核苷类逆转录酶抑制剂（NNRTI）（6.1%）：K103K/N（n = 2）、Y181C（n = 2）、G190G/A（n = 1）和P236P/L（n = 1）。在几乎所有患者中都观察到PR中的K20I和M36I等亚型特异性二级多态性。CRF02_AG和CRF06_cpx感染患者中耐药突变的发生频率相似（分别为12.8%和10.8%）。在重要的HLA表位内观察到一些亚型特异性多态性，包括RT中的B35、B7和A2，以及PR序列中的A*6802。根据研究时间，观察到的耐药突变很可能是传播而来的，但不能排除之前未记录的ART使用情况。
