Weight gain, body composition, and metabolic parameters of dolutegravir-based antiretroviral therapy versus standard of care in children and adolescents: an ancillary analysis of the ODYSSEY trial.

In the ≥14 kg cohort, dolutegravir-based ART was associated with a small but statistically non-significant increase in weight compared to standard of care at week 240.

• Adjusted mean difference (dolutegravir minus standard of care) for weight at week 240 was 1.0 kg (95% CI -0.2 to 2.2; p=0.095).
• The weight difference was driven by differences in first-line participants (ODYSSEY-A), where higher increases were also observed in height, waist circumference, and hip circumference.
• Median follow-up on randomised allocation was 287 weeks (IQR 240–311) on dolutegravir-based ART and 205 weeks (168–240) on standard of care in the ≥14 kg cohort.
• 792 children were randomly assigned (392 to dolutegravir and 400 to standard of care); 707 were in the ≥14 kg cohort.

Mid-upper-arm circumference (MUAC) was significantly greater with dolutegravir than standard of care in the ≥14 kg cohort at week 240.

• Adjusted mean difference for MUAC at week 240 was 0.4 cm (95% CI 0.0 to 0.8; p=0.030).
• This difference was driven by first-line ART participants.
• In the <14 kg cohort, there was a small non-significant difference in MUAC of 0.6 cm (95% CI -0.1 to 1.3; p=0.070).

BMI-for-age Z score, body fat percentage, and cross-sectional waist-to-height ratio were similar on dolutegravir-based ART and standard of care in the ≥14 kg cohort.

• Increases in BMI-for-age Z score, body fat percentage, and cross-sectional waist-to-height ratio were similar on dolutegravir-based ART and standard of care.
• At enrolment, median BMI-for-age Z score was -0.6 (IQR -1.4 to 0.1); 35 (5%) were overweight and six (1%) were obese.
• These findings indicate that indices defining excessive weight gain and central adiposity were similar with dolutegravir and other anchor drugs.

Dolutegravir-based ART was associated with significantly lower total cholesterol, triglycerides, and glucose compared to standard of care in the ≥14 kg cohort.

• Total cholesterol was lower with dolutegravir by -15.3 mg/dL (95% CI -21.0 to -9.5; p<0.0001).
• Triglycerides were lower with dolutegravir by -14.4 mg/dL (95% CI -25.2 to -3.6; p=0.0089).
• Glucose was lower with dolutegravir by -4.4 mg/dL (95% CI -6.8 to -1.9; p=0.0004).
• Standard of care in ODYSSEY-B (second-line ART) consisted predominantly of boosted protease inhibitors (195 [98%] of 200 participants), which are known to adversely affect lipids.

In the <14 kg cohort, changes in weight, weight-for-age, BMI-for-age, and height-for-age Z scores were similar between dolutegravir and standard of care.

• Changes in weight, weight-for-age, BMI-for-age, and height-for-age Z scores by 192 weeks were similar on dolutegravir and standard of care.
• There was a statistically significant difference in height of -2.5 cm (95% CI -4.5 to -0.5; p=0.016), indicating slightly less height gain with dolutegravir.
• Median enrolment age was 1.4 years (IQR 0.6 to 2.0) and median weight was 8.1 kg (5.4–10.0) in this cohort.
• 85 children were enrolled in the <14 kg cohort; 83 (98%) were Black African.
• Median follow-up on randomised allocation was 220 weeks (IQR 208–232) on dolutegravir-based ART and 144 weeks (127–192) on standard of care.

In the <14 kg cohort, no significant differences in lipid biomarkers were observed between dolutegravir and standard of care, but glucose decreased with standard of care and not with dolutegravir.

• No significant differences in lipid biomarkers were observed in the <14 kg cohort.
• Glucose decreased with standard of care but not with dolutegravir in this cohort.
• Standard of care for 32 (74%) of 43 participants in the <14 kg cohort was lopinavir-ritonavir as first-line or second-line treatment.

There were substantial treatment switches from standard of care to dolutegravir-based ART during extended follow-up, which required statistical adjustment.

• Treatment switches were substantial in the standard of care arm during extended follow-up.
• Treatment effects were estimated on randomised allocation, accounting for treatment switches through censoring and inverse-probability-of-censoring-weights.
• Median follow-up on randomised allocation was shorter in the standard of care arm (205 weeks, IQR 168–240) compared to the dolutegravir arm (287 weeks, IQR 240–311) in the ≥14 kg cohort, reflecting these switches.

The study population was predominantly Black African children with a median enrolment age of 12.2 years in the ≥14 kg cohort.

• In the ≥14 kg cohort, 623 (88%) were Black African, median enrolment age was 12.2 years (IQR 9.1 to 14.9), and median weight was 30.7 kg (IQR 23.4 to 43.0).
• 345 (49%) were female and 362 (51%) were male in the ≥14 kg cohort.
• Enrolled across 29 centres in Germany, Portugal, South Africa, Spain, Thailand, Uganda, Zimbabwe, and the UK.
• Children were enrolled between Sept 20, 2016, and Aug 26, 2019.