HIV viral suppression in children and adolescents 2 years after transition to dolutegravir: a multicentre cohort study

Abstract

Background: Treatment failure is common among children and adolescents with HIV. Antiretroviral therapy (ART) containing dolutegravir has recently been rolled out across Africa, though long-term real-world data in paediatric populations are lacking. Here, we report treatment outcomes among children and adolescents in Lesotho who transitioned from non-nucleoside reverse transcriptase inhibitor- (NNRTI-) to dolutegravir-based ART through two years’ follow-up. Methods: Data were derived from two open cohort studies in Lesotho. Children and adolescents aged < 18 years who transitioned from NNRTI- to dolutegravir-based ART at least 18 months before data closure were included. We report viral load results <12 months before, 12 (window: 6–17) months after, and 24 (window: 18–29) months after transition to dolutegravir. Associations of pre-transition demographic and clinical factors with 24-month viraemia were assessed through multivariable logistic regression. Results: Among 2126 included individuals, 1100 (51.7%) were female, median age at transition to dolutegravir was 14.0 years (interquartile range [IQR] 11.5–15.8), and median time taking ART at transition was 7.6 years (IQR 4.4–10.6). Among those with a viral load result at the respective time points, viral suppression to <50 copies/mL was achieved by 1635/1973 (82.9%) <12 months before, 1846/2012 (91.8%) 12 months after, and 1725/1904 (90.6%) 24 months after transition to dolutegravir. Pre-transition viraemia was associated with viraemia at 24 months, though >80% of individuals with pre-transition viraemia achieved resuppression to <50 copies/mL at 24 months. Conclusions: The proportion of children and adolescents with viral suppression increased after transition to dolutegravir, though further progress is needed to reach global targets.

Cohort profile: the Viral load Cohort North-East Lesotho (VICONEL) from 2016 to 2022 – cohort description, test volumes, predictors of viraemia, and the road ahead

“…We found that previously described associations of lowlevel viraemia (50-999 copies/mL) with subsequent viraemia ≥1000 copies/mL hold true also in the era of dolutegravir, supporting the 2021 change in World Health Organization guidelines lowering the viral load threshold for clinical action [7,21]. Overall, short- [22] and long-term viral load outcomes after changing from NNRTI-to dolutegravir-based ART were encouraging, with >95% of adults and >90% of children and adolescents with non-missing data at 24 months having viral suppression to <50 copies/mL [6,8]. However, our recent findings raise important concerns regarding emergent resistance to dolutegravir: among the few participants with persistent and/or recurring viraemia including at least one viral load ≥500 copies/mL at least 18 months after starting dolutegravir, dolutegravir resistance was observed for approx.…”

“…The former is achieved in part through a dashboard for clinicians and automated reports flagging persons with incident or repeated viraemia to facilitate clinical followup. Scientific evidence is generated through analysis of routine data [4][5][6][7][8], as well as nested observational [9][10][11][12] and interventional studies [13].…”

“…Starting in 2015, a consortium consisting of the Ministry of Health of Lesotho, the District Health Management Here, we report on cohort composition, test numbers, treatment outcomes, and factors associated with viraemia from the first seven years of the cohort (2016 to 2022), review the cohort's broader scientific findings so far, and outline the road ahead. [4][5][6][7][8], as well as nested observational [9][10][11][12] and interventional studies [13].…”