Predictors of long-term viral failure among Ugandan children and adults treated with antiretroviral therapy
Predictors of long-term viral failure among Ugandan children and adults treated with antiretroviral therapy
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DOI：
10.1097/qai.0b013e31814278c0
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发表时间：
2007-10-01
影响因子：
3.6
通讯作者：
Kekitiinwa, Adeodata
中科院分区：
文献类型：
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作者：
Kamya, Moses R.;Mayanja-Kizza, Harriet;Kekitiinwa, Adeodata
背景：HIV RNA 病毒载量检测费用昂贵，并且在资源有限的环境中通常无法进行。我们确定了病毒衰竭的预测因子，并记录了接受抗逆转录病毒治疗 (ART) 12 个月后出现病毒衰竭的患者的基因型突变。 方法：从 2004 年 4 月到 2005 年 6 月，连续招募了在乌干达一所大学诊所开始 ART 的初治患者。在基线时和每 3 至 6 个月收集一次临床信息、CD4 细胞计数和 HIV RNA 水平。使用多变量逻辑回归确定了病毒失败的独立预测因素。在基线以及 6 个月和 12 个月时测量了 8 名在 12 个月时病毒衰竭的患者的基因型耐药性。结果：526 名成人和 250 名儿童（0 至 18 岁）开始接受一线 ART 治疗方案，并随访 12 个月。 13% 的患者无法评估结果（79 例死亡，21 例退出）。与成人相比，儿童出现病毒感染失败的可能性几乎是成人的两倍（26% vs. 14%；P = 0.0001）。在成人中，病毒失败的唯一独立预测因子是司他夫定 (d4T)/拉米夫定 (3TC)/奈韦拉平 (NVP) 与齐多夫定 (ZDV)/3TC/依非韦伦 (EFV) 治疗（比值比 [OR] = 2.59，95% 置信区间 [CI]：1.20 至 5.59）。在儿童中，病毒失败的独立预测因素包括男性（OR = 2.44，95% CI：1.20至4.93）、基线CD4% < 5（OR = 2.69，95% CI：1.28至5.63）以及d4T/3TC/NVP与ZDV/3TC/EFV治疗（OR = 2.46，95% CI：1.23）至 4.90）。所有 8 名具有病毒突破和基因型耐药结果的患者均具有非核苷逆转录酶抑制剂 (NNRTI) 和 3TC 相关突变。结论：这些数据证明了 ART 在资源匮乏环境中的有效性。接受 d4T/3TC/NVP 方案的儿童和所有年龄段的患者更有可能出现病毒衰竭。我们的数据表明，乌干达常用的 ART 治疗方案开始后 6 个月或更长时间发生的病毒衰竭可能与 NNRTI 和 3TC 耐药病毒有关。
Background: HIV RNA viral load testing is costly and is generally unavailable in resource-limited settings. We identified predictors of viral failure and documented genotypic mutations in a subset of patients with viral failure after 12 months on antiretroviral therapy (ART).Methods: From April 2004 to June 2005, consecutive treatment-naive patients beginning ART at a university clinic in Uganda were enrolled. Clinical information, CD4 cell count, and HIV RNA level were collected at baseline and every 3 to 6 months. Independent predictors of viral failure were identified using multivariate logistic regression. Genotypic drug resistance for 8 patients with viral failure at 12 months was measured at baseline and at 6 and 12 months.Results: Five hundred twenty-six adults and 250 children (0 to 18 years of age) were started on first-line ART regimens and followed for 12 months. Outcomes could not be assessed in 13% of patients (79 died and 21 were withdrawn). Children were almost twice as likely to have viral failure compared with adults (26% vs. 14%; P= 0.0001). In adults, the sole independent predictor of viral failure was treatment with stavudine (d4T)/lamivudine (3TC)/nevirapine (NVP) versus zidovudine (ZDV)/3TC/efavirenz (EFV) (odds ratio [OR] =2.59, 95% confidence interval [CI]: 1.20 to 5.59). In children, independent predictors of viral failure included male gender (OR = 2.44, 95% CI: 1.20 to 4.93), baseline CD4% < 5 (OR = 2.69, 95% CI: 1.28 to 5.63), and treatment with d4T/3TC/NVP versus ZDV/3TC/EFV (OR = 2.46, 95% CI: 1.23 to 4.90). All 8 patients with viral breakthrough and genotypic drug resistance results had nonnucleoside reverse transcriptase inhibitor (NNRTI)- and 3TC-associated mutations.Conclusions: These data demonstrate the effectiveness of ART in a low-resource setting. Children and patients of all ages taking the d4T/3TC/NVP regimen were more likely to have viral failure. Our data suggest that viral failure occurring 6 months or more after the start of ART regimens commonly used in Uganda is likely to be associated with NNRTI- and 3TC-resistant virus.