Pediatric Day Hospital at Maputo Central Hospital, Maputo, Mozambique.
Pediatr Infect Dis J. 2009 Dec;28(12):e283-7. doi: 10.1097/INF.0b013e3181ba6c92.
Resistant virus may be selected by sub-optimal control of HIV-1 replication during antiretroviral treatment. The incidence and profile of resistance in children receiving World Health Organization-recommended treatment remains to be evaluated on a large scale.
Assessment of the frequency and profile of resistant virus in HIV-1-infected children, treated for at least 6 months with stavudine/zidovudine + lamivudine + nevirapine and presenting virological failure in a large access program in Maputo, Mozambique.
Cross-sectional evaluation of plasma HIV-1 viral load (VL) in 495 evaluable children among 512 treated for at least 6 months showed that 360 (72.7%) had a VL of <50 copies/mL of HIV-1 RNA. Genotypic resistance tests were performed in the 84 available samples from the 135 treated children with VL > or = 50 copies/mL: 92% of the viruses were resistant to lamivudine and/or nevirapine, and 15% were resistant to stavudine. Twenty children (24%) harbored virus with a extended spectrum of cross-resistance defined as resistance to the 3 drugs of the combination received by the child and/or at least 1 resistance to a drug to which the child had never been exposed (abacavir: 5%, tenofovir: 6%, didanosine: 3.5% and the new generation non nucleoside inhibitor, etravirine: 6%). The only factor identified by multivariate analysis as being associated with this extended resistance profile was the duration of treatment (aOR: 6.67 [95% CI: 1.24-35.93], P = 0.015 for treatment >24 months) with a per month increase of 1.09 (1.02-1.16) P = 0.007.
Residual viral replication in children receiving stavudine/zidovudine + lamivudine + nevirapine treatment is associated with a time-dependent risk of acquiring cross-resistance, including resistance to drugs currently used for second-line treatment and also to the new generation of non nucleoside reverse transcriptase inhibitors.
在抗逆转录病毒治疗期间，如果 HIV-1 复制的控制不理想，可能会选择耐药病毒。在世界卫生组织推荐的治疗方案下，接受治疗的儿童的耐药发生率和耐药谱仍需大规模评估。
评估在莫桑比克马普托一个大型治疗项目中，至少接受 6 个月齐多夫定/司他夫定+拉米夫定+奈韦拉平治疗，且病毒学治疗失败的 HIV-1 感染儿童中耐药病毒的发生频率和耐药谱。
在 512 名至少接受 6 个月治疗的患儿中，对 495 名可评估患儿进行了血浆 HIV-1 病毒载量（VL）的横断面评估，结果显示 360 名（72.7%）患儿的 HIV-1 RNA 病毒载量＜50 拷贝/mL。对 135 名 VL≥50 拷贝/mL 的治疗患儿中 84 份可用样本进行了基因型耐药检测：92%的病毒对拉米夫定和/或奈韦拉平耐药，15%对司他夫定耐药。20 名患儿（24%）携带具有广泛交叉耐药谱的病毒，定义为对患儿所接受联合用药的 3 种药物耐药，和/或对患儿从未接触过的药物耐药（阿巴卡韦：5%，替诺福韦：6%，地达诺辛：3.5%，新型非核苷类逆转录酶抑制剂依曲韦林：6%）。多因素分析确定的唯一与这种广泛耐药谱相关的因素是治疗时间（OR：6.67[95%CI：1.24-35.93]，P=0.015，治疗时间＞24 个月），每月增加 1.09（1.02-1.16），P=0.007。
接受齐多夫定/司他夫定+拉米夫定+奈韦拉平治疗的儿童中残留病毒复制与获得交叉耐药的时间依赖性风险相关，包括对目前用于二线治疗的药物以及新型非核苷类逆转录酶抑制剂的耐药。
