D'arminio Monforte Antonella, Tavelli Alessandro, Sala Matteo, Mondi Annalisa, Rusconi Stefano, Antinori Spinello, Puoti Massimo, Celesia Benedetto Maurizio, Taramasso Lucia, Saracino Annalisa, Antinori Andrea, Cozzi-Lepri Alessandro
Unit of Infectious Diseases ASST Santi Paolo e Carlo, Department of Health Sciences, Università degli Studi di Milano, ASST Santi Paolo e Carlo, via A. di Rudinì 8, 20142, Milan, Italy.
Icona Foundation, Milan, Italy.
J Antimicrob Chemother. 2023 Apr 3;78(4):933-945. doi: 10.1093/jac/dkad026.
To compare the long-term risk of treatment failure of dolutegravir-based ART in men and women in a real-life setting.
Persons living with HIV (PLWH) from the ICONA cohort were included if they had started dolutegravir in a two- or three-drug regimen as ART-naive or as virologically controlled ART-experienced. The primary endpoint was time to treatment failure (virological/clinical failure or dolutegravir discontinuation). Secondary endpoints were: time to dolutegravir discontinuation due to toxicity and to neuropsychiatric adverse events; and time to virological failure. Cox regression analyses focused on differences in outcomes by sex.
A total of 2304 PLWH (15% women) initiated dolutegravir-based therapy from ART-naive, and 1916 (19.8% women) while experienced. After a median follow-up of 2.2 (IQR: 0.9-3.9) years in ART-naive and 2.4 (IQR: 1.1-4.3) years in experienced, the 4-year cumulative probability of treatment failure was 33% (95% CI 30.5-35.1) and 20% (95% CI 17.8-22.3), respectively. In the multivariable analyses, in ART-naive the risk of treatment failure was higher for women, but not different after excluding women discontinuing dolutegravir for pregnancy concerns. We also observed a higher risk of discontinuation for toxicity in women (ART-naives: Adjusted Hazard Ratio (AHR): 1.56%; 95% CI: 1.03-2.37; ART-experienced: AHR: 1.53%; 95% CI: 1.01-2.32), although the absolute 4-year probability was low: 7.7% (95% CI 6.5-9.2) in ART-naive and 8.3% (95% CI 6.9-9.9) in experienced.
In our cohort of PLWH treated with dolutegravir-based regimens and followed up for up to 4 years, we observed a low risk of treatment failure and no evidence for a difference by sex, after excluding discontinuation due to pregnancy concerns. However, we observed a higher risk of dolutegravir discontinuation for toxicity in women.
比较在现实环境中，基于多替拉韦的抗逆转录病毒疗法（ART）在男性和女性中的长期治疗失败风险。
如果来自ICONA队列的艾滋病毒感染者（PLWH）作为初治患者或病毒学得到控制的经治患者，开始接受含多替拉韦的二联或三联药物方案治疗，则纳入研究。主要终点是治疗失败时间（病毒学/临床失败或停用多替拉韦）。次要终点包括：因毒性和神经精神不良事件停用多替拉韦的时间；以及病毒学失败时间。Cox回归分析重点关注不同性别在结局方面的差异。
共有2304例初治PLWH（15%为女性）开始接受基于多替拉韦的治疗，1916例经治患者（19.8%为女性）。初治患者的中位随访时间为2.2年（四分位间距：0.9 - 3.9年），经治患者为2.4年（四分位间距：1.1 - 4.3年），4年治疗失败的累积概率分别为33%（95%置信区间30.5 - 35.1）和20%（95%置信区间17.8 - 22.3）。在多变量分析中，初治患者中女性治疗失败的风险更高，但在排除因妊娠相关原因停用多替拉韦的女性后，性别差异不再显著。我们还观察到女性因毒性停药的风险更高（初治患者：调整后风险比（AHR）：1.56%；95%置信区间：1.03 - 2.37；经治患者：AHR：1.53%；95%置信区间：1.01 - 2.32），尽管4年的绝对概率较低：初治患者为7.7%（95%置信区间6.5 - 9.2），经治患者为8.3%（95%置信区间6.9 - 9.9）。
在我们这个接受基于多替拉韦方案治疗且随访长达4年的PLWH队列中，我们观察到治疗失败风险较低，且在排除因妊娠相关原因停药后，无性别差异证据。然而，我们观察到女性因毒性停用多替拉韦的风险更高。
