多替拉韦联合富马酸替诺福韦二吡呋酯-恩曲他滨用于男同性恋者和双性恋者的HIV暴露后预防

Dolutegravir with tenofovir disoproxil fumarate-emtricitabine as HIV postexposure prophylaxis in gay and bisexual men.

作者信息

McAllister John W, Towns Janet M, Mcnulty Anna, Pierce Anna B, Foster Rosalind, Richardson Robyn, Carr Andrew

机构信息

aHIV, Immunology & Infectious Diseases Unit and Centre for Applied Medical Research, St Vincent's Hospital, Sydney, New South Wales bMelbourne Sexual Health Centre cCentral Clinical School, Faculty of Medicine, Nursing and Health Sciences, Monash University, Melbourne, Victoria dSydney Sexual Health Centre, Sydney, New South Wales eDepartment of Infectious Diseases, The Alfred Hospital, Melbourne, Victoria fClinic 16, Northern Sydney Sexual Health, Sydney, New South Wales, Australia.

出版信息

AIDS. 2017 Jun 1;31(9):1291-1295. doi: 10.1097/QAD.0000000000001447.

DOI:10.1097/QAD.0000000000001447

PMID:28301425

Abstract

OBJECTIVES

Completion rates for HIV postexposure prophylaxis (PEP) are often low. We investigated the adherence and safety of dolutegravir (DTG; 50 mg daily) with tenofovir disoproxil fumarate-emtricitabine (TDF-FTC; 300/200 mg, respectively) as three-drug PEP in gay and bisexual men.

DESIGN

Open-label, single-arm study at three sexual health clinics and two emergency departments in Australia.

METHODS

In total, 100 HIV-uninfected gay and bisexual men requiring PEP received DTG and TDF-FTC for 28 days. The primary end point was PEP failure (premature PEP cessation or primary HIV infection through week 12). Additional end points were adherence by self-report (n = 98) and pill count (n = 55), safety, and plasma drug levels at day 28.

RESULTS

PEP completion was 90% (95% confidence interval 84-96%). Failures (occurring at a median 9 days, interquartile range 3-16) comprised loss to follow-up (9%) and adverse event resulting in study drug discontinuation (headache, 1%). No participant was found to acquire HIV through week 12. Adherence to PEP was 98% by self-report and in the 55 participants with corresponding pill count data. The most common clinical adverse events were fatigue (26%), nausea (25%), diarrhoea (21%), and headache (10%). There were only four grade 3-4 subjective adverse events. The most common laboratory adverse event was raised alanine aminotransferase (22%), but there was no case of clinical hepatitis. At day 28, the mean estimated glomerular filtration rate decrease was 14 ml/min/1.73m (SD 17, P = 0.001); an estimated glomerular filtration rate of less than 60 ml/min/1.73m occurred in 3%.

CONCLUSIONS

DTG with TDF-FTC is a well tolerated option for once-daily PEP.

摘要

目的

HIV暴露后预防（PEP）的完成率通常较低。我们调查了多替拉韦（DTG；每日50毫克）联合富马酸替诺福韦二吡呋酯-恩曲他滨（TDF-FTC；分别为300/200毫克）作为三药PEP方案在男同性恋者和双性恋男性中的依从性和安全性。

设计

在澳大利亚的三家性健康诊所和两家急诊科进行的开放标签单臂研究。

方法

总共100名需要PEP的未感染HIV的男同性恋者和双性恋男性接受DTG和TDF-FTC治疗28天。主要终点是PEP失败（在第12周之前过早停止PEP或原发性HIV感染）。其他终点包括自我报告的依从性（n = 98）和药丸计数的依从性（n = 55）、安全性以及第28天的血浆药物水平。

结果

PEP完成率为90%（95%置信区间84 - 96%）。失败情况（中位发生时间为9天，四分位间距为3 - 16天）包括失访（9%）和导致研究药物停用的不良事件（头痛，1%）。在第12周内未发现参与者感染HIV。自我报告的PEP依从性为98%，在有相应药丸计数数据的55名参与者中也是如此。最常见的临床不良事件为疲劳（26%）、恶心（25%）、腹泻（21%）和头痛（10%）。仅有4例3 - 4级主观不良事件。最常见的实验室不良事件是丙氨酸氨基转移酶升高（22%），但无临床肝炎病例。在第28天，估计肾小球滤过率平均下降14毫升/分钟/1.73平方米（标准差17，P = 0.001）；3%的人估计肾小球滤过率低于60毫升/分钟/1.73平方米。