多拉：在一项从多替拉韦或依非韦伦转换为基于多拉韦林的一线抗逆转录病毒治疗的IIIb期转换研究中，感染艾滋病毒的黑人女性48周的体重和代谢变化。
DORA: 48-week weight and metabolic changes in Black women with HIV, in a phase IIIb switch study from dolutegravir- or efavirenz- to doravirine-based first-line antiretroviral therapy.
作者信息
Woods Joana, Sokhela Simiso, Akpomiemie Godspower, Bosch Bronwyn, Möller Karlien, Bhaskar Esther, Kruger Chelsea, Manentsa Ncomeka, Tom Noxolo, Macholo Philadelphia, Chandiwana Nomathemba, Hill Andrew, Moorhouse Michelle, Venter Willem D F
机构信息
Wits Ezintsha, Faculty of Health Sciences, University of the Witwatersrand, Johannesburg, South Africa.
Department of Pharmacology and Therapeutics, University of Liverpool, Liverpool, UK.
出版信息
HIV Med. 2025 Jan;26(1):81-96. doi: 10.1111/hiv.13711. Epub 2024 Sep 17.
OBJECTIVES
Treatment-related weight gain and metabolic complications with antiretroviral integrase-based regimens, especially among Black women, suggest the need for alternative options.
METHODS
We conducted a 48-week, open-label, single-arm, single-centre, phase IIIb switch study to evaluate the tolerability, safety and efficacy of switching from stable efavirenz- or dolutegravir-based antiretroviral therapy to doravirine/lamivudine/tenofovir disoproxil fumarate in Black women.
RESULTS
The 101 participants enrolled (median age 35 years; interquartile range 31-40) were on efavirenz (n = 46; mean duration on therapy 1.7 years) or dolutegravir-based (n = 55; mean duration 1.5 years) antiretrovirals at screening. Retention at 48 weeks was 92/101 participants, and viral suppression was >90% throughout the study, with a single case of doravirine resistance (106 M, V108I and H221Y mutations). The mean weight percentage change at week 48 was 4.7% (95% confidence interval [CI] 3.0-6.5; p < 0.001), and the adjusted mean change was 2.7 kg (95% CI 1.50-3.98; p < 0.001); for efavirenz, the percentage change was 5.0% (95% CI 2.9-7.1; p < 0.001), and the adjusted weight gain was 3.5 kg (95% CI 1.93-5.13); for dolutegravir, the percentage change was 4.5% (95% CI 1.8-7.3; p < 0.001), and the adjusted weight gain was 2.1 kg (95% CI 0.26-3.90). Statistically significant decreases in lipid panel percent mean to week 48 included: total cholesterol -8.4% (95% CI -11.3 to -5.5; p < 0.001), triglycerides -10.4% (95% CI -16.4 to -4.4; p < 0.001) and high-density lipoprotein -14.8% (95% CI -18.5 to -11.2%; p < 0.001), with minor differences when disaggregating the mean percent change in lipids between previous efavirenz/dolutegravir regimens. Adverse events due to doravirine were few and mild.
CONCLUSIONS
Our findings suggest that a switch to doravirine from efavirenz or dolutegravir is safe and effective in Black women, with significant improvement in lipid profiles, but does not arrest progressive weight gain.
目的
基于抗逆转录病毒整合酶的治疗方案会导致与治疗相关的体重增加和代谢并发症，尤其是在黑人女性中，这表明需要其他选择。
方法
我们进行了一项为期48周、开放标签、单臂、单中心的IIIb期转换研究，以评估黑人女性从基于依非韦伦或多替拉韦的稳定抗逆转录病毒疗法转换为多拉韦林/拉米夫定/替诺福韦酯富马酸盐的耐受性、安全性和有效性。
结果
纳入的101名参与者（中位年龄35岁；四分位间距31 - 40岁）在筛查时接受依非韦伦（n = 46；平均治疗时长1.7年）或基于多替拉韦（n = 55；平均时长1.5年）的抗逆转录病毒药物治疗。48周时的留存率为92/101名参与者，并且在整个研究过程中病毒抑制率>90%，仅有1例多拉韦林耐药（106M、V108I和H221Y突变）。第48周时体重百分比的平均变化为4.7%（95%置信区间[CI] 3.0 - 6.5；p < 0.001），调整后的平均变化为2.7千克（95% CI 1.50 - 3.98；p < 0.001）；对于依非韦伦，百分比变化为5.0%（95% CI 2.9 - 7.1；p < 0.001），调整后的体重增加为3.5千克（95% CI 1.93 - 5.13）；对于多替拉韦，百分比变化为4.5%（95% CI 1.8 - 7.3；p < 0.001），调整后的体重增加为2.1千克（95% CI 0.26 - 3.90）。到第48周时，血脂指标平均百分比的统计学显著下降包括：总胆固醇 -8.4%（95% CI -11.3至 -5.5；p < 0.001）、甘油三酯 -10.4%（95% CI -16.4至 -4.4；p < 0.001）和高密度脂蛋白 -14.8%（95% CI -18.5至 -11.2%；p < 0.001），在区分先前依非韦伦/多替拉韦治疗方案之间血脂的平均百分比变化时差异较小。由多拉韦林引起的不良事件很少且轻微。
结论
我们的研究结果表明，从依非韦伦或多替拉韦转换为多拉韦林对黑人女性是安全有效的，血脂谱有显著改善，但并不能阻止体重的逐渐增加。
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