Dose Response for Starting and Stopping HIV Preexposure Prophylaxis for Men Who Have Sex With Men
Dose Response for Starting and Stopping HIV Preexposure Prophylaxis for Men Who Have Sex With Men
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DOI：
10.1093/cid/ciu916
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发表时间：
2015-03-01
影响因子：
11.8
通讯作者：
Anderson, Peter L.
中科院分区：
文献类型：
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作者：
Seifert, Sharon M.;Glidden, David V.;Anderson, Peter L.
背景本研究估计了每日替诺福韦酯富马酸/恩曲他滨（TDF/FTC）剂量的数量，以达到和维持（停药后）细胞内药物浓度，防止人类免疫缺陷病毒（HIV）感染的男性与男性发生性关系（MSM）。评价了来自30天每日TDF/FTC随后30天停药的密集药代动力学研究（“Cell-PrEP”[暴露前预防]）的外周血单核细胞（PBMC）和直肠单核细胞中的二磷酸替诺福韦（TFV-DP）浓度。使用从暴露前预防倡议研究中收集的PBMC得出的HIV风险降低的回归公式来计算推断的风险降低。还测定了直肠单核细胞中TFV-DP达到稳态所需的时间。21名未感染HIV的成年人参加了Cell-PrEP。基于PBMC TFV-DP浓度推断的HIV风险降低在5次每日剂量后达到99%（95%置信区间[CI]，69%-100%），并且在从稳态条件停止药物后7天内保持>90%。5剂后达到90%有效浓度（EC 90）的参与者比例为77%，7剂后为89%。5次给药后直肠单核细胞中自然对数[TFV-DP]的稳态百分比为88%（95% CI，66%-94%），7次给药后为94%（95% CI，78%-98%）。MSM的高PrEP活性通过约1周的每日给药实现。尽管停止PrEP后有效的细胞内药物浓度会持续几天，但合理的建议是在最后一次潜在的HIV暴露后继续给予PrEP 4周，这与暴露后预防的建议类似。
Background. This study estimated the number of daily tenofovir disoproxil fumarate/emtricitabine (TDF/FTC) doses required to achieve and maintain (after discontinuation) intracellular drug concentrations that protect against human immunodeficiency virus (HIV) infection for men who have sex with men (MSM).Methods. Tenofovir diphosphate (TFV-DP) concentrations in peripheral blood mononuclear cells (PBMCs) and rectal mononuclear cells from an intensive pharmacokinetic study ("Cell-PrEP" [preexposure prophylaxis]) of 30 days of daily TDF/FTC followed by 30 days off drug were evaluated. A regression formula for HIV risk reduction derived from PBMCs collected in the preexposure prophylaxis initiative study was used to calculate inferred risk reduction. The time required to reach steady state for TFV-DP in rectal mononuclear cells was also determined.Results. Twenty-one HIV-uninfected adults participated in Cell-PrEP. The inferred HIV risk reduction, based on PBMC TFV-DP concentration, reached 99% (95% confidence interval [CI], 69%-100%) after 5 daily doses, and remained >90% for 7 days after stopping drug from steady-state conditions. The proportion of participants reaching the 90% effective concentration (EC90) was 77% after 5 doses and 89% after 7 doses. The percentage of steady state for natural log [TFV-DP] in rectal mononuclear cells was 88% (95% CI, 66%-94%) after 5 doses and 94% (95% CI, 78%-98%) after 7 doses.Conclusions. High PrEP activity for MSM was achieved by approximately 1 week of daily dosing. Although effective intracellular drug concentrations persist for several days after stopping PrEP, a reasonable recommendation is to continue PrEP dosing for 4 weeks after the last potential HIV exposure, similar to recommendations for postexposure prophylaxis.