Lingering sex and age disparities in dolutegravir uptake among adults with HIV: A multi-country observational cohort study

IntroductionSince July 2019, the World Health Organization (WHO) has recommended dolutegravir (DTG)-based regimens as preferred first-line antiretroviral therapy (ART) for adults and adolescents living with HIV (DTG-for-All), a reversal of a 2018 safety alert on use of DTG-based regimens by women of reproductive age (WRA). We examined sex and age disparities in DTG uptake before and after DTG-for-All in the International epidemiology Databases to Evaluate AIDS (IeDEA). MethodsWe included patients [≥]16 years on or initiating treatment between January 2017 and July 2021 in 14 low- and middle-income countries where initial guidelines on DTG-based regimens for first-line ART either restricted use by WRA or had no such restrictions. We estimated the cumulative incidence of DTG uptake (CI-DTG) by sex and age group (aged 16-49 years vs. 50+ years), stratified by patient, clinic and setting characteristics. ResultsAmong 177,706 patients on ART during the study period, 51% were females aged 16-49 years, with 25% males aged 16-49, and 13% and 11%, respectively, females and males aged 50+. At the time of DTG-for-All, overall CI-DTG was 29.6% (95%CI: 29.4, 29.8); it was lower among females aged 16-49 (16.2%; 95%CI: 16.0-16.5) than males (41.1%; 95%CI: 40.6, 41.5), with no sex disparities among patients aged 50+ (females: 46.0%; males: 47.0%). While DTG uptake subsequently increased among all groups, by July 2021, it remained substantially lower among females 16-49 (66.4%; 95%CI: 66.1, 66.7), compared with males 16-49 and older females and males (75.8% to 77.5%). Concentrated in countries where initial guidelines on DTG restricted use by WRA, disparities in DTG uptake persisted at all health system levels and in both low-income and lower-middle income countries. ConclusionsWhile sex-age differentials in DTG uptake narrowed after WHOs DTG-for-All recommendation, lingering disparities uptake underscore the challenges of policy de-implementation when new evidence emerges. Key MessagesO_ST_ABSWhat is already known on this topicC_ST_ABSPrior research illuminated substantial sex and age group disparities in uptake of dolutegravir (DTG)-based antiretroviral therapy (ART) regimens among people with HIV (PLHIV)--disparities that emerged after the World Health Organization (WHO) issued a May 2018 drug safety alert for women of reproductive age (WRA) and persisted after subsequent guidance in July 2019 recommending DTG-based regimens as preferred first-line treatment for all adults and adolescents, irrespective of age and sex. What this study addsDrawing on real-world service delivery data from 72 clinics in 14 countries, this study documents the persistence of sex and age group disparities in DTG-based regimen uptake. Concentrated in low- and lower-middle income countries where national guidelines initially contained restrictions on use of DTG by WRA, these disparities remained substantial at two and three years after WHOs "dolutegravir for all" guidance among treatment-naive and treatment-experienced PLHIV and were observed at all health system levels. How this study might affect research, practice or policyOur study underscores the substantial lags that can occur in updating, disseminating, and translating new policy guidance into practice, as well as the challenges of de-implementing outdated policy recommendations when new evidence emerges--challenges that will remain relevant with new treatment regimens, such as injectable ART, on the horizon.