Vidya Madhavan, Saravanan Shanmugam, Uma Shanmugasundaram, Kumarasamy Nagalingeswaran, Sunil Solomon S, Kantor Rami, Katzenstein David, Ramratnam Bharat, Mayer Kenneth H, Suniti Solomon, Balakrishnan Pachamuthu
YRG Centre for AIDS Research and Education, Chennai, India.
Antivir Ther. 2009;14(7):1005-9. doi: 10.3851/IMP1411.
HIV type-1 (HIV-1) monitoring in resource-limited settings relies on clinical and immunological assessment. The objective of this study was to study the frequency and pattern of reverse transcriptase (RT) drug resistance among patients with immunological failure (IF) to first-line therapy.
A cross-sectional study of 228 patients with IF was done, of which 126 were drug-naive (group A) when starting highly active antiretroviral therapy (HAART) and 102 were exposed to mono/dual therapy prior to HAART initiation (group B). A validated in-house genotyping method and Stanford interpretation was used. Means, sd, median and frequencies (as percentages) were used to indicate the patient characteristics in each group. The chi(2) test and Fisher's exact test were used to compare categorical variables as appropriate. All analyses were performed using SPSS software, version 13.0. P-values <0.05 were considered to be statistically significant.
RT drug resistance mutations were found in 92% and 96% of patients in groups A and B, respectively. Median (interquartile range) CD4(+) T-cell count at failure was 181 cells/microl (18-999) and time to failure was 40 months (2-100). M184V (80% versus 75%), thymidine analogue mutations (63% versus 74%), Y181C (39% versus 39%) and K103N (29% versus 39%) were predominant RT mutations in both groups. Extensive nucleoside reverse transcriptase inhibitor cross-resistance mutations were observed in 51% and 26% of patients in group B and A, respectively.
Alternative strategies for initial therapy and affordable viral load monitoring could reduce resistance accumulations and preserve available drugs for future options in resource-limited settings.
在资源有限的环境中,1型人类免疫缺陷病毒(HIV-1)监测依赖于临床和免疫评估。本研究的目的是研究一线治疗免疫失败(IF)患者中逆转录酶(RT)耐药的频率和模式。
对228例IF患者进行了横断面研究,其中126例在开始高效抗逆转录病毒治疗(HAART)时未接受过治疗(A组),102例在HAART开始前接受过单药/双药治疗(B组)。采用经过验证的内部基因分型方法和斯坦福大学的解读标准。均值、标准差、中位数和频率(以百分比表示)用于描述每组患者的特征。适当情况下,使用卡方检验和Fisher精确检验比较分类变量。所有分析均使用SPSS软件13.0版进行。P值<0.05被认为具有统计学意义。
A组和B组分别有92%和96%的患者发现RT耐药突变。失败时CD4(+) T细胞计数的中位数(四分位间距)为181个细胞/微升(18 - 999),失败时间为40个月(2 - 100)。两组中主要的RT突变是M184V(80%对75%)、胸苷类似物突变(63%对74%)、Y181C(39%对39%)和K103N(29%对39%)。分别在B组和A组51%和26%的患者中观察到广泛的核苷类逆转录酶抑制剂交叉耐药突变。
在资源有限的环境中,初始治疗的替代策略和可负担的病毒载量监测可以减少耐药性积累,并为未来保留可用药物。