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

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.