Genital Tenofovir Concentrations Correlate With Protection Against HIV Infection in the CAPRISA 004 Trial: Importance of Adherence for Microbicide Effectiveness.
Genital Tenofovir Concentrations Correlate With Protection Against HIV Infection in the CAPRISA 004 Trial: Importance of Adherence for Microbicide Effectiveness.
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DOI：
10.1097/qai.0000000000000607
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发表时间：
2015-07-01
期刊：
影响因子：
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通讯作者：
Abdool Karim SS
中科院分区：
文献类型：
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作者：
Kashuba AD;Gengiah TN;Werner L;Yang KH;White NR;Karim QA;Abdool Karim SS
CAPRISA 004试验表明，性交给药的替诺福韦1%凝胶总体上减少了39%的HIV感染，持续使用时减少了54%。本分析的目的是确定其药代动力学-药效学关系，以防止艾滋病毒感染。在CAPRISA 004试验期间，将34名获得艾滋病毒的妇女（病例）的生殖器和全身替诺福韦浓度与302名随机选择的未感染艾滋病毒的妇女（对照）进行了比较。总共有336个宫颈阴道液（CVF），55个血浆，和23个配对的宫颈和阴道组织样本进行了测定，通过验证的方法替诺福韦和替诺福韦二磷酸盐（替诺福韦DP）检测。在8例（23.5%）病例和119例（39.4%）对照中检测到生殖道中的替诺福韦（p=0.076）。在生殖道可检测到替诺福韦的患者中，病例组CVF浓度中位数比对照组低97%，分别为476 ng/ml和13821 ng/ml（p=0.107）。共发现14.7%（5/34）的病例和32.8%（99/302）的对照组的替诺福韦CVF浓度高于100 ng/mL（比值比（OR）：0.35，p=0.037）。在较高的阈值下，发现8.8%（3/34）的病例和26.2%（79/302）的对照具有高于1000 ng/mL的替诺福韦CVF浓度（OR：0.27，p=0.036）。所有女性的血浆替诺福韦浓度均<1 ng/mL，病例组（0%）的检测频率低于对照组（16.7%）（p=0.031）。返回的用过的替诺福韦凝胶涂抹器和CVF浓度相关（斯皮尔曼r=0.22，p=0.001）。CVF中替诺福韦浓度≥ 100 ng/mL与65%（CI：6%; 87%）的HIV保护相关，而浓度≥ 1000 ng/mL与76%（CI：8%; 92%）的HIV感染保护相关。
The CAPRISA 004 trial showed that coitally-dosed tenofovir 1% gel reduced HIV acquisition by 39% overall and 54% when used consistently. The objective of this analysis was to ascertain its pharmacokinetic-pharmacodynamic relationship to protection against HIV acquisition. Genital and systemic tenofovir concentrations in 34 women who acquired HIV (cases) were compared to 302 randomly selected women who remained HIV uninfected (controls) during the CAPRISA 004 trial. In total, 336 cervicovaginal fluid (CVF), 55 plasma, and 23 paired cervical and vaginal tissue samples were assayed by validated methods for tenofovir and tenofovir diphosphate (tenofovir-DP) detection. Tenofovir was detected in the genital tract in 8(23.5%) cases and 119(39.4%) controls (p=0.076). Among those with detectable genital tract tenofovir, the median CVF concentrations were 97% lower in cases compared to controls, 476ng/ml versus 13821ng/ml (p=0.107). A total of 14.7% (5/34) of cases and 32.8 % (99/302) of controls were found to have tenofovir CVF concentrations above 100ng/mL (Odds Ratio (OR): 0.35, p=0.037). At a higher threshold, 8.8 %(3/34) of cases and 26.2 % (79/302) of controls were found to have tenofovir CVF concentrations above 1000ng/mL (OR: 0.27, p=0.036). Plasma tenofovir concentrations were <1ng/mL in all women and were less frequently detected in cases (0%) than controls (16.7 %) (p=0.031). Returned used tenofovir gel applicators and CVF concentrations were correlated (Spearman r=0.22, p=0.001). A tenofovir concentration of ≥100ng/mL in CVF was associated with 65% (CI: 6%; 87%) protection against HIV, while a ≥1000ng/mL concentration correlated with 76% (CI: 8%; 92%) protection against HIV infection.