Hospital Clínic de Barcelona, IDIBAPS, Barcelona, Spain.
PLoS One. 2012;7(12):e47391. doi: 10.1371/journal.pone.0047391. Epub 2012 Dec 6.
Consequences of lack of viral monitoring in predicting the effects of development of HIV drug resistance mutations during HAART in resource-limited settings (RLS) is still a matter of debate.
To assess, among HIV+ patients receiving their first-line HAART, prevalence of virological failure and genotypic resistance mutations pattern in a Médécins Sans Frontières/Ministry of Health programme in Busia District (Kenya).
Patients with HAART treatment for ≥12 months were eligible for the study and those with HIV-RNA ≥5000 copies/ml underwent genotypic study. Total HIV-1 RNA from Dried Blood Spots was extracted using Nuclisens method.
926 patients were included. Among 274 (29.6%) patients with detectable viral load, 55 (5.9%) experienced treatment failure (viral load >5.000 copies/ml); 61.8% were female and 10 (18.2%) had clinical failure. Median CD4 cell count was 116 cell/mm3 (IQR: 54-189). Median HIV-RNA was 32,000 copies/ml (IQR: 11000-68000). Eighteen out of 55 (33%) samples could be sequenced on PR and RT genes, with resistance associated mutations (RAMs) in 15 out of 18 samples (83%). Among patients carrying RAMs, 12/15 (81%) harboured RAMs associated to thymidine analogues (TAMs). All of them (100%) showed M184V resistance associated mutation to lamivudine as well as NNRTI's RAMS.
Virological failure rate in resource-limited settings are similar to those observed in developed countries. Resistance mutation patterns were concordant with HAART received by failing patients. Long term detectable viral load confers greater probability of developing resistance and as a consequence, making difficult to find out a cost-effective subsequent treatment regimen.
在资源有限的环境下(RLS),缺乏病毒监测对预测 HIV 耐药突变发展对高效抗逆转录病毒治疗(HAART)效果的影响仍然存在争议。
评估在布西亚区(肯尼亚)无国界医生组织/卫生部的一个项目中,接受一线 HAART 的 HIV+患者中病毒学失败的流行率和基因型耐药突变模式。
接受 HAART 治疗≥12 个月的患者有资格参加研究,HIV-RNA≥5000 拷贝/ml 的患者进行基因型研究。使用 Nuclisens 方法从干血斑中提取总 HIV-1 RNA。
共纳入 926 例患者。在 274 例(29.6%)可检测到病毒载量的患者中,有 55 例(5.9%)发生治疗失败(病毒载量>5.000 拷贝/ml);61.8%为女性,10 例(18.2%)发生临床失败。中位 CD4 细胞计数为 116 个细胞/mm3(IQR:54-189)。中位 HIV-RNA 为 32,000 拷贝/ml(IQR:11000-68000)。55 例中有 18 例(33%)可对 PR 和 RT 基因进行测序,其中 18 例(83%)样本中存在耐药相关突变(RAMs)。在携带 RAMs 的患者中,15 例(81%)中存在与胸腺嘧啶类似物(TAMs)相关的 RAMs。所有患者(100%)均显示对拉米夫定和非核苷类逆转录酶抑制剂(NNRTI)RAMs的 M184V 耐药相关突变。
资源有限环境下的病毒学失败率与发达国家观察到的相似。耐药突变模式与失败患者接受的 HAART 一致。长期可检测到的病毒载量增加了耐药的可能性,因此难以找到具有成本效益的后续治疗方案。