Using the adherence-efficacy relationship of emtricitabine and tenofovir disoproxil fumarate to calculate background hiv incidence: a secondary analysis of a randomized, controlled trial.
Using the adherence-efficacy relationship of emtricitabine and tenofovir disoproxil fumarate to calculate background hiv incidence: a secondary analysis of a randomized, controlled trial.
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DOI：
10.1002/jia2.25744
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发表时间：
2021-05
影响因子：
6
通讯作者：
Anderson PL
中科院分区：
文献类型：
--
作者：
Glidden DV;Das M;Dunn DT;Ebrahimi R;Zhao Y;Stirrup OT;Baeten JM;Anderson PL
用于HIV暴露前预防（PrEP）的新药的随机试验与恩曲他滨和富马酸替诺福韦酯（F/TDF）进行比较，没有安慰剂组。我们在一项新型PrEP药物的随机试验中，使用F/TDF的良好表征的依从性-疗效关系来反算（非PrEP）反事实背景HIV发病率（bHIV），并估计比较疗效（与反事实bHIV）。DISCOVER试验（ClinicalTrials.gov：NCT 02842086）随机分配了5387名男男性行为者（MSM）和男男性行为者的跨性别女性，并证明恩曲他滨和替诺福韦艾拉酚胺（F/TAF）非劣效于F/TDF（HIV发病率比[IRR] 0.47，95% CI：0.19至1.15）。对所有诊断为HIV的患者和随机10%的队列患者评估了干血斑（DBS）中的替诺福韦二磷酸盐（TFV-DP）水平。我们使用了一个贝叶斯模型与扩散先验分布，来自已建立的数据有关的替诺福韦二磷酸水平的艾滋病毒预防效果。这一先验，结合DISCOVER中的F/TDF血清转换率和二磷酸替诺福韦水平，得出了关于反事实bHIV的贝叶斯推断。F/TAF和F/TDF组分别有6例和11例基线后HIV感染（0.14 vs. 0.25/100人年[PY]）。在接受F/TDF治疗的11名受试者中，10名受试者的二磷酸替诺福韦水平较低，无一名受试者的二磷酸替诺福韦水平较高;在HIV阴性对照组中，5%的人-年TFV-DP水平较低，9%的人-年TFV-DP水平较高，86%的人-年TFV-DP水平较高。反事实bHIV的无信息先验分布，结合TFV-DP水平-疗效关系的先验分布，得出反事实bHIV的后验分布为3·4例感染/100 PY（0.80贝叶斯可信区间[CrI] 1·9至5·9），这表明与bHIV相比，F/TAF的中位HIV疗效为96%（0.95 CrI [88%至99%]），F/TDF为93%（0.95 CrI [87%至96%]）。基于药物浓度与PrEP预防有效性的既定联系，贝叶斯框架可用于估计包括F/TDF-对照组的随机化、活性对照PrEP试验中的合成非PrEP对照组。
Randomized trials of new agents for HIV pre‐exposure prophylaxis (PrEP) compare against emtricitabine and tenofovir disoproxil fumarate (F/TDF), without a placebo group. We used the well‐characterized adherence‐efficacy relationship for F/TDF to back‐calculate the (non‐PrEP) counterfactual background HIV incidence (bHIV) in a randomized trial of a novel PrEP agent and estimate comparative efficacy (to counterfactual bHIV). The DISCOVER trial (ClinicalTrials.gov: NCT02842086) randomized 5387 men who have sex with men (MSM) and transgender women who have sex with men and demonstrated non‐inferiority of emtricitabine and tenofovir alafenamide (F/TAF) to F/TDF (HIV incidence rate ratio [IRR] 0·47, 95% CI: 0·19 to 1.15). Tenofovir diphosphate (TFV‐DP) levels in dried blood spots (DBS) were assessed for all diagnosed with HIV and in a random 10% of the cohort. We used a Bayesian model with a diffuse prior distribution, derived from established data relating tenofovir diphosphate levels to HIV prevention efficacy. This prior, combined with the F/TDF seroconversion rate and tenofovir diphosphate levels in DISCOVER, yielded Bayesian inferences on the counterfactual bHIV. There were six versus 11 postbaseline HIV infections (0.14 vs. 0.25/100 person‐years [PY]) on F/TAF and F/TDF respectively. Of the 11 on F/TDF, 10 had low, none had medium and one had high tenofovir diphosphate levels; among HIV‐negative controls, 5% of the person‐time years had low, 9% had medium and 86% had high TFV‐DP levels. A non‐informative prior distribution for counterfactual bHIV, combined with the prior for TFV‐DP level‐efficacy relationship, yielded a posterior counterfactual bHIV of 3·4 infections/100 PY (0.80 Bayesian credible interval [CrI] 1·9 to 5·9), which suggests a median HIV efficacy of 96% (0.95 CrI [88% to 99%]) for F/TAF and 93% (0.95 CrI [87% to 96%]) for F/TDF compared to bHIV. Based on the established connection of drug concentrations to PrEP prevention efficacy, a Bayesian framework can be used to estimate a synthetic non‐PrEP control group in randomized, active‐controlled PrEP trials that include a F/TDF‐comparator group.
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影响因子：
15.8
作者：
Baeten JM;Heffron R;Kidoguchi L;Mugo NR;Katabira E;Bukusi EA;Asiimwe S;Haberer JE;Morton J;Ngure K;Bulya N;Odoyo J;Tindimwebwa E;Hendrix C;Marzinke MA;Ware NC;Wyatt MA;Morrison S;Haugen H;Mujugira A;Donnell D;Celum C;Partners Demonstration Project Team
通讯作者：
Partners Demonstration Project Team
DOI：
10.1097/qai.0000000000000172
发表时间：
2014-07-01
期刊：
Journal of acquired immune deficiency syndromes (1999)
影响因子：
--
作者：
Donnell D;Baeten JM;Bumpus NN;Brantley J;Bangsberg DR;Haberer JE;Mujugira A;Mugo N;Ndase P;Hendrix C;Celum C
通讯作者：
Celum C
影响因子：
168.9
作者：
Baeten, Jared M.;Donnell, Deborah;Stringer, Jeffrey
通讯作者：
Stringer, Jeffrey
影响因子：
168.9
作者：
Mayer, Kenneth H.;Molina, Jean-Michel;Thompson, Melanie A.;Anderson, Peter L.;Mounzer, Karam C.;De Wet, Joss J.;DeJesus, Edwin;Jessen, Heiko;Grant, Robert M.;Ruane, Peter J.;Wong, Pamela;Ebrahimi, Ramin;Zhong, Lijie;Mathias, Anita;Callebaut, Christian;Collins, Sean E.;Das, Moupali;McCallister, Scott;Brainard, Diana M.;Brinson, Cynthia;Clarke, Amanda;Coll, Pep;Post, Frank A.;Hare, C. Bradley
通讯作者：
Hare, C. Bradley
影响因子：
1.7
作者：
Cahill S;Taylor SW;Elsesser SA;Mena L;Hickson D;Mayer KH
通讯作者：
Mayer KH