含马拉维若方案预防女性感染艾滋病毒的安全性和耐受性：一项2期随机试验
Safety and Tolerability of Maraviroc-Containing Regimens to Prevent HIV Infection in Women: A Phase 2 Randomized Trial.
作者信息
Gulick Roy M, Wilkin Timothy J, Chen Ying Q, Landovitz Raphael J, Amico K Rivet, Young Alicia M, Richardson Paul, Marzinke Mark A, Hendrix Craig W, Eshleman Susan H, McGowan Ian, Cottle Leslie M, Andrade Adriana, Marcus Cheryl, Klingman Karin L, Chege Wairimu, Rinehart Alex R, Rooney James F, Andrew Philip, Salata Robert A, Siegel Marc, Manabe Yukari C, Frank Ian, Ho Ken, Santana Jorge, Stekler Joanne D, Swaminathan Shobha, McCauley Marybeth, Hodder Sally, Mayer Kenneth H
机构信息
From Weill Cornell Medicine, New York, New York; Fred Hutchinson Cancer Research Center and University of Washington, Seattle, Washington; University of California, Los Angeles, Los Angeles, California; University of Michigan, Ann Arbor, Michigan; Johns Hopkins University School of Medicine, Baltimore, Maryland; University of Pittsburgh and University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania; University of North Carolina, Chapel Hill, North Carolina; National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Maryland; ViiV Healthcare, Durham, North Carolina; Gilead Sciences, Foster City, California; Case Western Reserve University, Cleveland, Ohio; The George Washington University and FHI 360, Washington, DC; Perelman School of Medicine of the University of Pennsylvania, Philadelphia, Pennsylvania; University of Puerto Rico School of Medicine, San Juan, Puerto Rico; Rutgers New Jersey Medical School, Newark, New Jersey; West Virginia University, Morgantown, West Virginia; and Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, Massachusetts.
出版信息
Ann Intern Med. 2017 Sep 19;167(6):384-393. doi: 10.7326/M17-0520. Epub 2017 Aug 22.
BACKGROUND
Maraviroc (MVC) is a candidate drug for HIV preexposure prophylaxis (PrEP).
OBJECTIVE
To assess the safety and tolerability of MVC-containing PrEP over 48 weeks in U.S. women at risk for HIV infection.
DESIGN
Phase 2 randomized, controlled, double-blinded study of 4 antiretroviral regimens used as PrEP. (ClinicalTrials.gov: NCT01505114).
SETTING
12 clinical research sites of the HIV Prevention Trials Network and AIDS Clinical Trials Group.
PARTICIPANTS
HIV-uninfected women reporting condomless vaginal or anal intercourse with at least 1 man with HIV infection or unknown serostatus within 90 days.
INTERVENTION
MVC only, MVC-emtricitabine (FTC), MVC-tenofovir disoproxil fumarate (TDF), and TDF-FTC (control).
MEASUREMENTS
At each visit, clinical and laboratory (including HIV) assessments were done. Primary outcomes were grade 3 and 4 adverse events and time to permanent discontinuation of the study regimen. All randomly assigned participants were analyzed according to their original assignment.
RESULTS
Among 188 participants, 85% completed follow-up, 11% withdrew early, and 4% were lost to follow-up; 19% discontinued their regimen prematurely. The number discontinuing and the time to discontinuation did not differ among regimens. Grade 3 or 4 adverse events occurred in 5 (MVC), 13 (MVC-FTC), 9 (MVC-TDF), and 8 (TDF-FTC) participants; rates did not differ among regimens. One death (by suicide) occurred in the MVC-TDF group but was judged not to be related to study drugs. Of available plasma samples at week 48 (n = 126), 60% showed detectable drug concentrations. No new HIV infections occurred.
LIMITATIONS
Participants were not necessarily at high risk for HIV infection. The regimen comprised 3 pills taken daily. The study was not powered for efficacy.
CONCLUSION
Maraviroc-containing PrEP regimens were safe and well-tolerated compared with TDF-FTC in U.S. women. No new HIV infections occurred, although whether this was due to study drugs or low risk in the population is uncertain. Maraviroc-containing PrEP for women may warrant further study.
PRIMARY FUNDING SOURCE
National Institutes of Health.
背景
马拉维若（MVC）是一种用于HIV暴露前预防（PrEP）的候选药物。
目的
评估含MVC的PrEP在美国有HIV感染风险的女性中应用48周的安全性和耐受性。
设计
对4种用作PrEP的抗逆转录病毒方案进行的2期随机、对照、双盲研究。（ClinicalTrials.gov：NCT01505114）。
地点
HIV预防试验网络和艾滋病临床试验组的12个临床研究地点。
参与者
报告在90天内与至少1名HIV感染或血清学状态不明的男性有无保护措施的阴道或肛交的未感染HIV的女性。
干预措施
仅用MVC、MVC-恩曲他滨（FTC）、MVC-替诺福韦酯（TDF）以及TDF-FTC（对照）。
测量指标
每次访视时进行临床和实验室（包括HIV）评估。主要结局为3级和4级不良事件以及研究方案永久停用时间。所有随机分配的参与者均按其原始分配情况进行分析。
结果
188名参与者中，85%完成随访，11%提前退出，4%失访；19%过早停用其方案。各方案之间的停药人数和停药时间无差异。5名（MVC组）、13名（MVC-FTC组）、9名（MVC-TDF组）和8名（TDF-FTC组）参与者发生3级或4级不良事件；各方案之间发生率无差异。MVC-TDF组发生1例死亡（自杀），但判定与研究药物无关。在第48周时可获得的血浆样本（n = 126）中，60%显示出可检测到的药物浓度。未发生新的HIV感染。
局限性
参与者不一定有高的HIV感染风险。该方案包括每日服用3片药。该研究未设定效力以评估疗效。
结论
在美国女性中，与TDF-FTC相比，含马拉维若的PrEP方案安全且耐受性良好。未发生新的HIV感染，尽管这是由于研究药物还是人群中风险较低尚不确定。含马拉维若的女性PrEP可能值得进一步研究。
主要资金来源
美国国立卫生研究院。
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