Department of Pathology, Johns Hopkins University School of Medicine, 720 Rutland Avenue, Baltimore, MD 21205, USA.
AIDS. 2011 Apr 24;25(7):911-7. doi: 10.1097/QAD.0b013e328344fedc.
In the Post Exposure Prophylaxis of Infants (PEPI)-Malawi trial, infants received up to 14 weeks of extended nevirapine (NVP) or extended NVP with zidovudine (NVP + ZDV) to prevent postnatal HIV transmission. We examined emergence and persistence of NVP resistance in HIV-infected infants who received these regimens prior to HIV diagnosis.
Infant plasma samples collected at 14 weeks of age were tested using the ViroSeq HIV Genotyping System and a sensitive point mutation assay, LigAmp (for K103N and Y181C). Samples collected at 6 and 12 months of age were analyzed using LigAmp.
At 14 weeks of age, NVP resistance was detected in samples from 82 (75.9%) of 108 HIV-infected infants. Although the frequency of NVP resistance detected by ViroSeq was lower in the extended NVP + ZDV arm than in the extended NVP arm, the difference was not statistically significant (38/55 = 69.1% vs. 44/53 = 83.0%, P = 0.12). Similar results were obtained using LigAmp. Using LigAmp, the proportion of infants who still had detectable NVP resistance at 6 and 12 months was similar among infants in the two study arms (at 6 months: 17/20 = 85.0% for extended NVP vs. 21/26 = 80.8% for extended NVP + ZDV, P = 1.00; at 12 months: 9/16 = 56.3% for extended NVP vs.10/13 = 76.9% for extended NVP + ZDV, P = 0.43).
Infants exposed to extended NVP or extended NVP + ZDV had high rates of NVP resistance at 14 weeks of age, and resistant variants frequently persisted for 6-12 months. Frequency and persistence of NVP resistance did not differ significantly among infants who received extended NVP only vs. extended NVP + ZDV prophylaxis.
在婴儿暴露后预防(PEPI)-马拉维试验中,婴儿接受了长达 14 周的扩展奈韦拉平(NVP)或扩展 NVP 联合齐多夫定(NVP+ZDV)治疗,以预防产后 HIV 传播。我们检查了在 HIV 诊断之前接受这些方案的 HIV 感染婴儿中出现和持续的 NVP 耐药情况。
在 14 周龄时收集婴儿血浆样本,使用 ViroSeq HIV 基因分型系统和敏感点突变检测 LigAmp(用于 K103N 和 Y181C)进行检测。在 6 个月和 12 个月时收集的样本使用 LigAmp 进行分析。
在 14 周龄时,在 108 名 HIV 感染婴儿中,有 82 名(75.9%)的样本中检测到 NVP 耐药。尽管在扩展 NVP+ZDV 臂中通过 ViroSeq 检测到的 NVP 耐药率低于扩展 NVP 臂,但差异无统计学意义(38/55=69.1%vs.44/53=83.0%,P=0.12)。使用 LigAmp 也得到了类似的结果。使用 LigAmp,在两个研究臂中的婴儿在 6 个月和 12 个月时仍有可检测到的 NVP 耐药的比例相似(在 6 个月时:扩展 NVP 组为 20/20=85.0%,扩展 NVP+ZDV 组为 26/26=80.8%,P=1.00;在 12 个月时:扩展 NVP 组为 16/16=56.3%,扩展 NVP+ZDV 组为 13/13=76.9%,P=0.43)。
暴露于扩展 NVP 或扩展 NVP+ZDV 的婴儿在 14 周龄时具有很高的 NVP 耐药率,耐药变异体在 6-12 个月内经常持续存在。仅接受扩展 NVP 治疗与接受扩展 NVP+ZDV 预防的婴儿之间,NVP 耐药的频率和持续时间没有显著差异。