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拉丁美洲和加勒比地区在获取基于多替拉韦的抗逆转录病毒疗法方面持续存在性别差异:一项使用2017年至2022年数据的回顾性观察研究结果

Persistent sex disparities in access to dolutegravir-based antiretroviral therapy in Latin America and the Caribbean: results from a retrospective observational study using data from 2017 to 2022.

作者信息

Fonseca Fernanda F, Ranadive Paridhi, Shepherd Bryan E, Ferreira Flavia G F, Rodríguez Maria F, Machado Daisy M, Rouzier Vanessa, Varela Diana, Maruri Fernanda, Ribeiro Peter, Grinsztejn Beatriz, Wagner Cardoso Sandra, Veloso Valdiléa G, Castilho Jessica L, Jalil Emilia M

机构信息

AIDS Health Care Foundation, Global Program, Sao Paulo, Brazil.

Fiocruz, Instituto Nacional de Infectologia Evandro Chagas, Rio de Janeiro, Brazil.

出版信息

J Int AIDS Soc. 2025 Jul;28(7):e26470. doi: 10.1002/jia2.26470.

Abstract

INTRODUCTION

Despite its reversal in July 2019, the World Health Organization warning issued in May 2018 of potential teratogenicity associated with dolutegravir (DTG) may have produced persistent sex disparities in access to DTG. We compared DTG uptake of people with HIV (PWH) by sex in Latin America and the Caribbean (LAC) and its potential impact on virologic outcomes.

METHODS

We evaluated DTG initiation among antiretroviral therapy (ART)-naïve and -experienced cisgender PWH ≥16 years of age after DTG availability in Brazil (February/2017), Chile (August/2019), Haiti (November/2018) and Honduras (December/2018). Time was divided into pre- (before May/2018), during- (May/2018-July/2019) and post- (after July/2019) warning periods. We examined interactions of sex, age and calendar era with multivariable modified Poisson regression models and Cox proportional hazard models for the outcomes of DTG initiation among ART-naïve and ART-experienced PWH, respectively, and HIV RNA <50 copies/ml in the first year of therapy among ART-naïve PWH, adjusting for site and tuberculosis.

RESULTS

Among 4622 ART-naïve PWH, 3853 (83%) initiated DTG. ART-naïve females aged 16-49 years were less likely to initiate DTG compared to males of the same age both in the pre/during-warning (adjusted prevalence ratio [aPR]: 0.75 [95% confidence interval (95% CI): 0.71-0.80]) and in the post-warning periods (aPR: 0.97 [95% CI: 0.95-1.00]). Among 16,154 ART-experienced PWH, 9236 (57%) initiated DTG. ART-experienced females 16-49 years were less likely to initiate DTG compared to males of the same age in the pre/during-warning (adjusted hazard ratio [aHR]: 0.69 [95% CI: 0.66-0.73]) and post-warning periods (aHR: 0.79 [95% CI: 0.70-0.90]). This sex difference was not observed among older ART-experienced females and males pre/during-warning (aHR: 1.06 [95% CI: 0.99-1.14]). Compared to starting ART without DTG, DTG-based ART use was associated with a higher likelihood of HIV RNA suppression in the first year (aPR = 1.10 [95% CI: 1.04-1.16]). In the post-warning period, females aged 16-49 years had a likelihood of viral suppression similar to males of the same age (aPR: 1.03 [95% CI: 0.96-1.10]), which did not change after adjusting for DTG use (aPR: 1.03 [95% CI: 0.97-1.11]).

CONCLUSIONS

Despite the updated guidelines recommending DTG for all PWH, there are persistent sex disparities in the access to DTG in LAC, especially among females within the reproductive age.

摘要

引言

尽管世界卫生组织在2019年7月撤销了相关警告,但在2018年5月发布的关于多替拉韦(DTG)可能具有致畸性的警告,可能导致在获取DTG方面持续存在性别差异。我们比较了拉丁美洲和加勒比地区(LAC)感染艾滋病毒者(PWH)中按性别划分的DTG使用情况及其对病毒学结果的潜在影响。

方法

我们评估了在巴西(2017年2月)、智利(2019年8月)、海地(2018年11月)和洪都拉斯(2018年12月)DTG上市后,年龄≥16岁的初治和经治的顺性别PWH中DTG的起始使用情况。时间分为警告前(2018年5月之前)、警告期间(2018年5月 - 2019年7月)和警告后(2019年7月之后)三个时期。我们分别使用多变量修正泊松回归模型和Cox比例风险模型,研究性别、年龄和日历时期与初治和经治PWH中DTG起始使用情况的相互作用,以及初治PWH在治疗第一年中HIV RNA <50拷贝/ml的情况,并对研究地点和结核病进行了校正。

结果

在4622名初治PWH中,3853名(83%)开始使用DTG。在警告前/期间,16 - 49岁的初治女性开始使用DTG的可能性低于同年龄男性(调整后的患病率比[aPR]:0.75 [95%置信区间(95%CI):0.71 - 0.80]),在警告后时期也是如此(aPR:0.97 [95%CI:0.95 - 1.00])。在16154名经治PWH中,9236名(57%)开始使用DTG。在警告前/期间,16 - 49岁的经治女性开始使用DTG的可能性低于同年龄男性(调整后的风险比[aHR]:0.69 [95%CI:0.66 - 0.73]),在警告后时期也是如此(aHR:0.79 [95%CI:0.70 - 0.90])。在年龄较大的经治女性和男性中,在警告前/期间未观察到这种性别差异(aHR:1.06 [95%CI:0.99 - 1.14])。与不使用DTG开始抗逆转录病毒治疗(ART)相比,使用基于DTG的ART在第一年实现HIV RNA抑制的可能性更高(aPR = 1.10 [95%CI:1.04 - 1.16])。在警告后时期,16 - 49岁的女性病毒抑制的可能性与同年龄男性相似(aPR:1.03 [95%CI:0.96 - 1.10]),在对DTG使用情况进行校正后这一情况没有改变(aPR:1.03 [95%CI:0.97 - 1.11])。

结论

尽管更新后的指南建议所有PWH使用DTG,但在LAC地区获取DTG方面仍存在持续的性别差异,尤其是在育龄女性中。

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