Vignoles Moira, Barboni Graciela, Agosti María R, Quarleri Jorge, García Mariel K, Ayala Silvia González, Salomón Horacio
National Reference Center for AIDS, School of Medicine, University of Buenos Aires, Buenos Aires, Argentina.
Antivir Ther. 2009;14(8):1175-81. doi: 10.3851/IMP1461.
The aim of this study was to describe the frequency of minority populations of viruses carrying mutations K103N and M184V in drug-naive HIV type-1 (HIV-1)-infected children, and to further evaluate their effect on the selection of drug-resistant viruses within highly active antiretroviral therapy (HAART).
Newly diagnosed vertically HIV-1-infected children were evaluated. The HIV-1 pol gene was sequenced for subtyping and antiretroviral drug resistance analysis. Standard genotypic sequencing and sequence-selective real-time PCR (SPCR) to quantify minority viral populations were used.
From December 2004 to July 2006, we included 35 children who were studied at baseline and during their first HAART regimen (follow-up median time 29.4 months). Of them, 82.9% were infected with intersubtype B/F recombinant variants. At baseline, all children had a drug-susceptible viral population that was studied by bulk sequencing. SPCR showed that 4 children had between 2-10% of M184V, 11 had <0.7%, 18 had no detectable mutation and 2 could not be amplified. No K103N minority populations were found. Once under HAART, children who had 2-10% of M184V at baseline further selected it in percentages >20% in less time than those with -0.1-0.6% or without minority populations (P=0.01).
It was shown that having 2-10% of M184V at baseline enhanced its selection in high percentages in a short time after HAART initiation. Further research regarding the presence of minority quasispecies before initiation of HAART in large paediatric populations should be undertaken to evaluate their clinical effect during HAART.
本研究旨在描述初治的1型人类免疫缺陷病毒（HIV-1）感染儿童中携带K103N和M184V突变的病毒少数群体的频率，并进一步评估它们对高效抗逆转录病毒治疗（HAART）中耐药病毒选择的影响。
对新诊断的垂直感染HIV-1的儿童进行评估。对HIV-1 pol基因进行测序以进行亚型分析和抗逆转录病毒药物耐药性分析。使用标准基因分型测序和序列选择性实时PCR（SPCR）来定量少数病毒群体。
从2004年12月至2006年7月，我们纳入了35名儿童，在基线期和他们的首个HAART治疗方案期间对其进行研究（随访中位时间29.4个月）。其中，82.9%感染了B/F亚型间重组变体。在基线时，所有儿童通过群体测序研究均有药物敏感的病毒群体。SPCR显示，4名儿童有2%-10%的M184V，11名儿童<0.7%，18名儿童未检测到突变，2名儿童无法扩增。未发现K103N少数群体。一旦接受HAART，基线时有2%-10% M184V的儿童比那些有-0.1%-0.6%或没有少数群体的儿童在更短时间内将其选择比例提高到>20%（P=0.01）。
结果表明，基线时有2%-10%的M184V会在HAART开始后的短时间内促使其在高比例中被选择。应在大量儿科人群中对HAART开始前少数准种的存在进行进一步研究，以评估它们在HAART期间的临床影响。
