暴露前预防治疗试验中感染 HIV 的患者的耐药情况。

Drug resistance among patients who acquired HIV infection in a preexposure prophylaxis trial.

机构信息

Virologie, Hôpital Saint-Louis, Assistance Publique Hôpitaux de Paris.

INSERM UMR 941, Université de Paris Diderot, Sorbonne Paris Cité.

出版信息

AIDS. 2018 Oct 23;32(16):2353-2361. doi: 10.1097/QAD.0000000000001960.

DOI:10.1097/QAD.0000000000001960

PMID:30096070

Abstract

BACKGROUND

The IPERGAY ANRS trial showed that on-demand preexposure prophylaxis (PrEP) with tenofovir (TDF) and emtricitabine (FTC) was highly effective in preventing HIV infection among highly exposed MSM. Here, we analyzed drug resistance-associated mutations (RAMs) among all participants who acquired HIV infection during this trial.

METHODS

Resistance was analyzed on frozen plasma at the time of HIV diagnosis among participants enrolled in the double-blind and open-label phases of the ANRS IPERGAY trial. Reverse transcriptase sequencing was performed, using population-based and ultradeep sequencing (454 GS Flex). Adherence was measured by pill counting and by plasma tenofovir and FTC assay.

RESULTS

During the trial, 31 participants were diagnosed with HIV-1 infection (subtype B, 64.5%), using antigen/antibody immune assay in 29 cases and plasma HIV RNA assay in two. The median plasma HIV-1 RNA level was 5.52 log10 copies/ml. Drug resistance was tested in 12 participants before starting PrEP, in six assigned to TDF/FTC group and in 13 assigned to placebo group. Primary resistance to nucleoside reverse transcriptase inhibitors (zidovudine) and/or nonnucleoside reverse transcriptase inhibitors was detected in six participants (19%; 95% confidence interval 7-42). No major or minor TDF-resistant or FTC-resistant variants were detected.

CONCLUSION

No TDF or FTC resistance-associated mutations were found among participants who acquired HIV in the ANRS IPERGAY trial.

摘要

背景

IPERGAY ANRS 试验表明，按需暴露前预防（PrEP）用替诺福韦（TDF）和恩曲他滨（FTC）对高度暴露的男男性行为者（MSM）预防 HIV 感染非常有效。在此，我们分析了这项试验中所有感染 HIV 的参与者的耐药相关突变（RAMs）。

方法

在 ANRS IPERGAY 试验的双盲和开放标签阶段入组的参与者中，在 HIV 诊断时对冷冻血浆进行了耐药分析。使用基于人群的和超深度测序（454 GS Flex）进行逆转录酶测序。通过计算药丸数量和检测血浆替诺福韦和 FTC 来测量依从性。

结果

在试验期间，31 名参与者被诊断为 HIV-1 感染（亚型 B，64.5%），29 例使用抗原/抗体免疫检测，2 例使用血浆 HIV RNA 检测。中位血浆 HIV-1 RNA 水平为 5.52 log10 拷贝/ml。在开始 PrEP 之前，对 12 名参与者进行了耐药性检测，其中 6 名被分配到 TDF/FTC 组，13 名被分配到安慰剂组。在 6 名参与者（19%；95%置信区间 7-42）中检测到对核苷逆转录酶抑制剂（齐多夫定）和/或非核苷逆转录酶抑制剂的原发性耐药。未检测到主要或次要的 TDF 耐药或 FTC 耐药变异。