替诺福韦酯/恩曲他滨暴露前预防研究中HIV血清阳转者的特征：HPTN 067/ADAPT研究
Characterization of HIV Seroconverters in a TDF/FTC PrEP Study: HPTN 067/ADAPT.
作者信息
Sivay Mariya V, Li Maoji, Piwowar-Manning Estelle, Zhang Yinfeng, Hudelson Sarah E, Marzinke Mark A, Amico Rivet K, Redd Andrew, Hendrix Craig W, Anderson Peter L, Bokoch Kevin, Bekker Linda-Gail, van Griensven Frits, Mannheimer Sharon, Hughes James P, Grant Robert, Eshleman Susan H
机构信息
*Department of Pathology, Johns Hopkins University School of Medicine, Baltimore, MD; †Vaccine and Infectious Disease Division, Fred Hutchinson Cancer Research Center, Seattle, WA; ‡Department of Health Behavior and Health Education, School of Public Health, University of Michigan, Ann Arbor, MI; §Department of Medicine, Johns Hopkins University School of Medicine, Baltimore, MD; ‖Division of Intramural Research, National Institute of Allergy and Infectious Diseases, National Institute of Health, Bethesda, MD; ¶Division of Clinical Pharmacology, Johns Hopkins University School of Medicine, Baltimore, MD; #Department of Pharmaceutical Sciences, University of Colorado Anschutz Medical Campus, Aurora, CO; **FHI 360, Durham, NC; ††Faculty of Health Sciences, University of Cape Town, Cape Town, South Africa; ‡‡Department of Epidemiology and Biostatistics, University of California San Francisco School of Medicine, San Francisco, CA; §§Departments of Medicine and Epidemiology, Columbia University Affiliation at Harlem Hospital, New York, NY; ‖‖Columbia University Mailman School of Public Health, New York, NY; ¶¶Department of Biostatistics, University of Washington, Seattle, WA; and ##University of California, San Francisco Gladstone Institutes, San Francisco, CA.
出版信息
J Acquir Immune Defic Syndr. 2017 Jul 1;75(3):271-279. doi: 10.1097/QAI.0000000000001374.
BACKGROUND
HIV Prevention Trials Network (HPTN) 067/ADAPT evaluated tenofovir disoproxil fumarate/emtricitabine (TDF/FTC) pre-exposure prophylaxis (PrEP) in women (South Africa) and men who have sex with men (Thailand, US). Participants received once-weekly directly observed therapy (DOT) of TDF/FTC, and were then randomized to daily, time-driven, or event-driven PrEP. This report describes characterization of 12 HIV seroconversion events in this trial.
METHODS
HIV rapid testing was performed at study sites. Retrospective testing included fourth generation assays, HIV RNA testing, Western blot, an HIV-1/2 discriminatory assay, resistance testing, and antiretroviral drug testing.
RESULTS
Six of the 12 seroconverters received TDF/FTC in the DOT phase, but were not randomized (3 were acutely infected at enrollment; 2 were infected during the DOT phase; 1 was not randomized because of pregnancy). One of the 6 randomized participants had acute infection at randomization but was not diagnosed for 3-4 months because HIV rapid tests were nonreactive; continued daily PrEP use was associated with false-negative antibody tests and low HIV RNA levels. The 5 participants infected after randomization included 4 with low adherence to the PrEP regimen, and one who reported a 7-day period without dosing before infection. Three participants had TDF/FTC resistance (M184I, K65R), including 2 who received only 4 once-weekly TDF/FTC doses; most TDF/FTC mutations were detected by next generation sequencing only.
CONCLUSIONS
In HPTN 067/ADAPT, participants who acquired HIV infection had infrequent PrEP dosing or low/suboptimal adherence. Sensitive assays improved detection of HIV infection and drug resistance. Drug resistance was observed with limited PrEP exposure.
背景
艾滋病预防试验网络（HPTN）067/ADAPT研究在女性（南非）和男男性行为者（泰国、美国）中评估了替诺福韦酯/恩曲他滨（TDF/FTC）暴露前预防（PrEP）措施。参与者接受每周一次的TDF/FTC直接观察治疗（DOT），然后被随机分配至每日、定时或事件驱动的PrEP组。本报告描述了该试验中12例HIV血清转化事件的特征。
方法
在研究地点进行HIV快速检测。回顾性检测包括第四代检测、HIV RNA检测、免疫印迹法、HIV-1/2鉴别检测、耐药性检测和抗逆转录病毒药物检测。
结果
12例血清转化者中有6例在DOT阶段接受了TDF/FTC治疗，但未被随机分组（3例在入组时急性感染；2例在DOT阶段感染；1例因怀孕未被随机分组）。6例随机分组的参与者中有1例在随机分组时急性感染，但因HIV快速检测呈阴性而在3 - 4个月后才被诊断出来；持续每日使用PrEP与抗体检测假阴性和低HIV RNA水平有关。随机分组后感染的5名参与者中，4例对PrEP方案依从性低，1例报告在感染前有7天未服药。3例参与者出现TDF/FTC耐药（M184I、K65R），其中2例仅接受了4次每周一次的TDF/FTC剂量；大多数TDF/FTC突变仅通过下一代测序检测到。
结论
在HPTN 067/ADAPT研究中，感染HIV的参与者PrEP服药频率低或依从性差/不理想。灵敏的检测方法提高了HIV感染和耐药性的检测。在PrEP暴露有限的情况下观察到了耐药性。
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