Exploring predictors of HIV-1 virologic failure to long-acting cabotegravir and rilpivirine: a multivariable analysis.
Exploring predictors of HIV-1 virologic failure to long-acting cabotegravir and rilpivirine: a multivariable analysis.
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DOI：
10.1097/qad.0000000000002883
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发表时间：
2021-07-15
期刊：
影响因子：
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通讯作者：
van Lunzen J
中科院分区：
文献类型：
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作者：
Cutrell AG;Schapiro JM;Perno CF;Kuritzkes DR;Quercia R;Patel P;Polli JW;Dorey D;Wang Y;Wu S;Van Eygen V;Crauwels H;Ford SL;Baker M;Talarico CL;Clair MS;Jeffrey J;White CT;Vanveggel S;Vandermeulen K;Margolis DA;Aboud M;Spreen WR;van Lunzen J
在3个3期试验中，每4周或8周肌肉注射一次长效卡博特重力韦（CAB）和利匹韦林（RPV）的有效性和安全性已经得到证实。在这里，与48周病毒学失败相关的因素被事后评估。采用logistic回归模型，对1039例初治长效CAB+RPV的成人数据进行多变量分析，以检验基线病毒和参与者因素、给药方案和药物浓度对确诊病毒学失败（CVF）发生的影响。在一个单独的模型中，进一步评估与CVF相关的基线因素，以了解单独存在或联合存在时的CVF风险。总体而言，1.25% （n = 13/1039）的参与者经历了CVF。前病毒RPV耐药相关突变（RAMs）、HIV-1亚型A6/A1、较高的BMI（与第8周CAB谷浓度相关）和较低的第8周RPV谷浓度与CVF几率增加显著相关（P < 0.05）（除RPV谷浓度在基线时可知外）。没有或只有一个基线因素的参与者很少（0.4%）有CVF。只有至少两个基线因素的组合（3.4%,n = 35/1039）与CVF风险增加相关（25.7%,n = 9/35）。CVF是一种罕见的多因素事件，在3期研究（FLAIR、ATLAS和ATLAS- 2m）中，CVF在长效CAB+RPV组的发生率约为1%。存在至少两种前病毒RPV ram、HIV-1亚型A6/A1和/或BMI至少30 kg/m2与CVF风险增加相关。这些发现支持在常规临床实践中使用长效CAB+RPV。
Efficacy and safety of long-acting cabotegravir (CAB) and rilpivirine (RPV) dosed intramuscularly every 4 or 8 weeks has been demonstrated in three Phase 3 trials. Here, factors associated with virologic failure at Week 48 were evaluated post hoc. Data from 1039 adults naive to long-acting CAB+RPV were pooled in a multivariable analysis to examine the influence of baseline viral and participant factors, dosing regimen and drug concentrations on confirmed virologic failure (CVF) occurrence using a logistic regression model. In a separate model, baseline factors statistically associated with CVF were further evaluated to understand CVF risk when present alone or in combination. Overall, 1.25% (n = 13/1039) of participants experienced CVF. Proviral RPV resistance-associated mutations (RAMs), HIV-1 subtype A6/A1, higher BMI (associated with Week 8 CAB trough concentration) and lower Week 8 RPV trough concentrations were significantly associated (P < 0.05) with increased odds of CVF (all except RPV trough are knowable at baseline). Few participants (0.4%) with zero or one baseline factor had CVF. Only a combination of at least two baseline factors (observed in 3.4%; n = 35/1039) was associated with increased CVF risk (25.7%, n = 9/35). CVF is an infrequent multifactorial event, with a rate of approximately 1% in the long-acting CAB+RPV arms across Phase 3 studies (FLAIR, ATLAS and ATLAS-2M) through Week 48. Presence of at least two of proviral RPV RAMs, HIV-1 subtype A6/A1 and/or BMI at least 30 kg/m2 was associated with increased CVF risk. These findings support the use of long-acting CAB+RPV in routine clinical practice.