Machado Elizabeth S, Lambert John S, Watson Douglas C, Afonso Adriana O, da Cunha Silvia M, Nogueira Susie A, Caride Elena, Oliveira Ricardo H, Sill Anne M, DeVico Anthony, Tanuri Amilcar
Serviço de Doenças Infecciosas e Parasitárias, Hospital Universitário Clementino Fraga Filho, Rio de Janeiro, Brazil.
J Clin Virol. 2004 May;30(1):24-31. doi: 10.1016/j.jcv.2003.08.001.
Antiretroviral therapy is provided by the Brazilian Ministry of Health to eligible HIV-infected individuals. Based on clinical and immunological classification, the Brazilian guidelines recommend dual or triple therapy for children. However, the development of drug-resistant strains or poor adherence to therapy could impact the efficacy of this approach.
We examined relationships between RNA levels, CD4+ T-cell counts, treatment history, and the prevalence of drug-resistant variants in a cohort of HIV-1-infected children in Rio de Janeiro, Brazil.
Direct sequencing of reverse transcriptase and protease genes from plasma was performed. Virologic and CD4+ T-cell counts responses to therapy were assessed by changes in HIV-1 RNA levels and CD4+ T-cell counts from baseline.
Thirty-seven patients were receiving dual therapy and 38 were on triple therapy at enrollment, segregated by antiretroviral history. Both groups had a higher increase in CD4+ T cell counts and a lower viral load in pre-treatment antiretroviral-naïve subjects. Notably, there was a direct correlation between the higher frequencies of drug-resistance mutations and cross-resistance with previous usage of antiretroviral (ARV) therapy in both groups. Non-B subtypes isolates were found in 21.3% of samples. A smaller increase in CD4+ T cell counts was found between non-B subtypes when compared to B-subtypes.
These results suggest that less immunological recovery and a higher number of mutations related to drug resistance were associated with previous usage of ARV and consequent higher time under drug selective pressure in these HIV-infected Brazilian children. These facts suggest the preferential use of triple drug combination as first line regimen in children.
巴西卫生部为符合条件的艾滋病毒感染者提供抗逆转录病毒治疗。根据临床和免疫学分类，巴西指南建议对儿童采用双重或三重疗法。然而，耐药菌株的出现或对治疗的依从性差可能会影响这种治疗方法的疗效。
我们研究了巴西里约热内卢一组感染HIV-1的儿童中RNA水平、CD4+T细胞计数、治疗史与耐药变异体患病率之间的关系。
对血浆中的逆转录酶和蛋白酶基因进行直接测序。通过HIV-1 RNA水平和CD4+T细胞计数相对于基线的变化来评估对治疗的病毒学和CD4+T细胞计数反应。
根据抗逆转录病毒治疗史，37例患者在入组时接受双重疗法，38例接受三重疗法。两组在治疗前未接受过抗逆转录病毒治疗的受试者中，CD4+T细胞计数增加更高，病毒载量更低。值得注意的是，两组中耐药突变的较高频率与先前使用抗逆转录病毒（ARV）治疗的交叉耐药之间存在直接相关性。在21.3%的样本中发现了非B亚型分离株。与B亚型相比，非B亚型的CD4+T细胞计数增加较小。
这些结果表明，在这些感染艾滋病毒的巴西儿童中，免疫恢复较差以及与耐药相关的突变数量较多与先前使用ARV以及随后在药物选择压力下的较长时间有关。这些事实表明在儿童中优先使用三联药物组合作为一线治疗方案。
