Greater dapivirine release from the dapivirine vaginal ring is correlated with lower risk of HIV-1 acquisition: a secondary analysis from a randomized, placebo-controlled trial.
Greater dapivirine release from the dapivirine vaginal ring is correlated with lower risk of HIV-1 acquisition: a secondary analysis from a randomized, placebo-controlled trial.
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DOI：
10.1002/jia2.25634
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发表时间：
2020-11
影响因子：
6
通讯作者：
MTN-020/ASPIRE Study Team
中科院分区：
文献类型：
--
作者：
Brown ER;Hendrix CW;van der Straten A;Kiweewa FM;Mgodi NM;Palanee-Philips T;Marzinke MA;Bekker LG;Soto-Torres L;Hillier SL;Baeten JM;MTN-020/ASPIRE Study Team
含有25 mg抗逆转录病毒达匹韦林的阴道环已被证明在降低女性性感染HIV-1风险方面有效;然而，不完美的环使用可能会稀释临床试验中的疗效估计。返回的环中残留的达匹韦林量可能反映了产品使用的程度，允许在持续使用的情况下估计HIV保护作用。我们测量了2012年8月至2015年6月在2629名非洲女性中进行的达匹韦林阴道环安慰剂对照试验中返回的环中达匹韦林的含量。I/II期研究确定，当持续使用超过28天时，从环中释放的达匹韦林平均超过4 mg，释放≤0.9 mg表明未使用。我们在多变量考克斯模型中，使用返回环中的残留达匹韦林作为HIV-1感染的时间依赖性协变量，评估了与环使用水平相关的相对风险降低，包括多项探索性分析，旨在估计HIV-1感染时间不确定性下的疗效上限。所有模型均针对与HIV风险和依从性相关的基线协变量进行了调整。与安慰剂相比，残留达匹韦林水平表明至少有一些使用（>0.9 mg，一个月释放）与HIV-1感染风险相对降低48%相关（95%置信区间（CI）：21%至66%; p = 0.002）。解释HIV-1感染时间的潜在错误分类的探索性分析估计，与安慰剂相比，释放> 4 mg时，HIV-1风险降低75%至91%。结果仅限于年龄<25岁的女性亚组，这些亚组往往具有较低的依从性，通常与总体一致。在一项随机试验的次要分析中，残留达匹韦林水平（依从性的客观指标）与HIV-1保护相关。使用环的时间与大约50%的保护相关，探索性分析表明，更一致的使用具有更高的保护。达匹韦林阴道环是实现完全可逆、长效、女性发起的谨慎预防HIV-1方法的第一种方法。
A vaginal ring containing 25 mg of the antiretroviral dapivirine has demonstrated efficacy in reducing women’s risk of sexually acquiring HIV‐1; however, imperfect ring use likely diluted efficacy estimates in clinical trials. The amount of dapivirine remaining in returned rings may reflect the extent of product use, permitting estimation of HIV protection in the context of consistent use. We measured the amount of dapivirine in returned rings from a placebo‐controlled trial of the dapivirine vaginal ring conducted between August 2012 and June 2015 among 2629 African women. Phase I/II studies established that greater than 4 mg of dapivirine on average is released from the ring when used consistently over 28 days and ≤0.9 mg released suggested non‐use. We assessed the relative risk reduction associated with levels of ring use using residual dapivirine in returned rings as a time‐dependent covariate for HIV‐1 infection in multivariable Cox models, including multiple exploratory analyses designed to estimate upper limits of efficacy given uncertainty in timing of HIV‐1 acquisition. All models were adjusted for baseline covariates associated with HIV risk and adherence. Residual dapivirine levels indicating at least some use (>0.9 mg released over a month) were associated with a 48% relative reduction in HIV‐1 acquisition risk (95% confidence interval (CI): 21% to 66%; p = 0.002) compared to the placebo. Exploratory analyses accounting for potential misclassification in timing of HIV‐1 acquisition estimated 75% to 91% HIV‐1 risk reduction with> 4 mg released when compared to placebo. Results limited to the subgroup of women <25 years of age, who tended to have lower adherence, were generally consistent to those overall. Residual dapivirine levels, an objective measure of adherence, were correlated with HIV‐1 protection in a secondary analysis of a randomized trial. Periods of ring use were associated with approximately 50% protection, with exploratory analyses suggesting higher protection with more consistent use. The dapivirine vaginal ring is the first method to fulfil the promise of a fully reversible, long‐acting, woman‐initiated approach for discreet HIV‐1 prevention.
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影响因子：
3.8
作者：
Nel, Annalene;Haazen, Wouter;van Niekerk, Neliette
通讯作者：
van Niekerk, Neliette
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：
10.9745/ghsp-d-13-00010
发表时间：
2013-08
期刊：
Global health, science and practice
影响因子：
--
作者：
Ross J;Stover J
通讯作者：
Stover J
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
DOI：
10.1097/qai.0000000000000158
发表时间：
2014-07-01
影响因子：
3.6
作者：
Corneli, Amy L.;Deese, Jennifer;Van Damme, Lut
通讯作者：
Van Damme, Lut