DISCUSSION
obesity, weight gain
OBESITY, TYPE 2 DIABETES MELLITUS
This is the first paediatric study to compare folate, vitamin B12 and MCV levels in children and adolescents receiving dolutegravir versus non‐dolutegravir ART. We found the levels of plasma folate at weeks 4 and ≥96 and RBC folate at week ≥96 were higher in those on dolutegravir than SOC, with fewer children in the DTG arm having plasma folate levels below the normal range at week ≥96. There was also a marginally higher proportion of children and adolescents on dolutegravir with RBC folate above the normal range at ≥96 weeks (15% DTG and 10% SOC). However, we found no evidence for a difference in treatment effect by weight for plasma or RBC folate, which would have suggested a dose−response effect for dolutegravir. We showed no difference between treatment arms in vitamin B12 at week ≥96 or in change in MCV from baseline over follow‐up.These results are in line with those observed in the folate sub‐study of the randomized ADVANCE trial which compared serum folate in women receiving dolutegravir‐based regimens with those on an efavirenz‐based regimen [Folate uptake from the intestine could be enhanced by dolutegravir through its effect on the proton‐coupled folate transporter (PCFT), which is the main folate transporter working at acid pH [In the ODYSSEY main trial, children in the dolutegravir arm gained 1 kg more weight on average and grew better [The results of our sub‐study provide reassuring results that dolutegravir‐based ART is not associated with low folate or B12 levels. However, the study showed that dolutegravir leads to increased plasma and RBC folate levels, although the mechanisms are poorly understood. Overall, higher haemoglobin and a lower number of children with insufficient plasma folate levels in the DTG arm compared to SOC indicate a better haematological health in children and adolescents receiving DTG‐based treatment.Dolutegravir has been associated with increased weight gain, obesity and new‐onset type 2 diabetes mellitus among adults, including pregnant women initiating or transitioning to dolutegravir‐based ART [The sub‐study was constrained to three urban research centres in Uganda, hence this may limit the generalizability of the results. Another limitation is that RBC folate was not collected at baseline, and therefore, we cannot evaluate the difference in RBC folate change over time between DTG and SOC arms. However, participants were in a randomized controlled trial, and baseline RBC folate would likely be similar between arms, enabling a fair comparison between dolutegravir‐ and non‐dolutegravir‐based ART regimens. All assessments were performed in one laboratory using validated assays which minimizes measurement bias.