Center for AIDS Prevention Studies and the Division of Infectious Diseases, University of California, San Francisco, CA 94105, USA.
J Int AIDS Soc. 2013 Jun 3;16(1):18449. doi: 10.7448/IAS.16.1.18449.
Routine HIV viral load (VL) testing is not available in India. We compared test performance characteristics of immunologic failure (IF) against the gold standard of virologic failure (VF), examined evolution of drug resistance among those who stayed on a failing regimen because they did not meet criteria for IF and assessed implications for second-line therapy.
Participants on first-line highly active antiretroviral therapy (HAART) in Bangalore, India, were monitored for 24 months at six-month intervals, with CD4 count, VL and genotype, if VL>1000 copies/ml. Standard WHO criteria were used to define IF; VF was defined as having two consecutive VL>1000 copies/ml or one VL>10,000 copies/ml. Resistance was assessed using standard International AIDS Society-USA (IAS-USA) recommendations.
Of 522 participants (67.6% male, mean age of 37.5; 85.1% on nevirapine-based and 40.4% on d4T-containing regimens), 57 (10.9%) had VF, 38 (7.3%) had IF and 13 (2.5%) had both VF and IF. The sensitivity of immunologic criteria to detect VF was 22.8%, specificity was 94.6% and positive predictive value was 34.2%. Forty-four participants with VF only continued on their failing first-line regimen; by the end of the study period, 90.9% had M184V, 63.6% had thymidine analogue mutations (TAMs), 34.1% had resistance to tenofovir, and 63.6% had resistance to etravirine.
WHO IF criteria have low sensitivity for detecting VF, and the presence of IF poorly predicts VF. Relying on CD4 counts leads to unnecessary switches to second-line HAART and continuation of failing regimens, jeopardizing future therapeutic options. Universal access to VL monitoring would avoid costly switches to second-line HAART and preserve future treatment options.
印度常规 HIV 病毒载量（VL）检测不可用。我们比较了免疫失败（IF）与病毒学失败（VF）的金标准的检测性能特征，检查了因不符合 IF 标准而继续使用失败方案的患者中耐药性的演变，并评估了对二线治疗的影响。
在班加罗尔，印度的一线高效抗逆转录病毒治疗（HAART）参与者每六个月监测 24 个月，CD4 计数、VL 和基因型，如果 VL>1000 拷贝/ml。使用标准的世卫组织标准来定义 IF；VF 定义为连续两次 VL>1000 拷贝/ml 或一次 VL>10,000 拷贝/ml。使用标准的国际艾滋病协会-美国（IAS-USA）建议评估耐药性。
在 522 名参与者（67.6%为男性，平均年龄 37.5；85.1%使用基于奈韦拉平的方案，40.4%使用包含 d4T 的方案）中，57 名（10.9%）出现 VF，38 名（7.3%）出现 IF，13 名（2.5%）同时出现 VF 和 IF。免疫标准检测 VF 的敏感性为 22.8%，特异性为 94.6%，阳性预测值为 34.2%。仅出现 VF 的 44 名参与者继续使用他们失败的一线方案；在研究结束时，90.9%出现 M184V，63.6%出现胸苷类似物突变（TAMs），34.1%对替诺福韦耐药，63.6%对依曲韦林耐药。
世卫组织 IF 标准对检测 VF 的敏感性较低，IF 的存在不能很好地预测 VF。依靠 CD4 计数会导致不必要地切换到二线 HAART 并继续使用失败的方案，从而危及未来的治疗选择。普遍获得 VL 监测将避免昂贵的二线 HAART 切换，并保留未来的治疗选择。
