Background: In previous clinical trials and cohort studies, dolutegravir (DTG) has been associated with rises in body weight and clinical obesity. These effects have been most pronounced in black people and women; the use of tenofovir disoproxil fumarate (TDF) is associated with lower body weight, compared to tenofovir alafenamide (TAF), abacavir or NRTI sparing treatment.
Methods: In the 96 week NAMSAL trial, 613 treatment naïve patients in Cameroun were randomised to TDF/3TC/DTG or TDF/3TC/EFV. Body weight was measured at baseline and Week 48. In the 96-week ADVANCE trial, 1053 treatment naïve patients in South Africa were randomised to TAF/FTC/DTG, TDF/FTC/DTG or TDF/FTC/EFV. Body weight was measured at baseline and every 12 weeks; DEXA scans evaluated limb and trunk fat at baseline, Week 48 and Week 96. For both trials, changes in body weight, Body Mass Index (BMI), and trunk fat (ADVANCE only) were compared between treatments.
Results: In the NAMSAL trial, mean weight rose +7.3% for TDF/3TC/DTG versus +5.3% for TDF/3TC/EFV (p< 0.001); treatment-emergent clinical obesity (BMI>30kg/m2) was recorded for 12% on TDF/3TC/DTG versus 5% for TDF/3TC/EFV (p=0004). BMI rose +1.7 kg/m2 for TDF/3TC/DTG versus +1.2kg/m2 for TDF/3TC/EFV. In ADVANCE (Results in Table), there were progressive, linear rises in body weight to Week 96 for women treated with TAF/FTC/DTG and TDF/FTC/DTG (Table 1); in men, mean body weight rose in the DTG arms to Week 48 and then stabilised to Week 96. Trunk fat also rose significantly in the TAF/FTC/DTG arm of ADVANCE.
Conclusions: In the NAMSAL and ADVANCE trials first-line DTG is associated with rises in body weight, clinical obesity and increased trunk fat. These rises are higher if used in combination with TAF/FTC. Rises in body weight on TAF/FTC/DTG are progressive: longer-term follow up and re-analysis of other studies is required to evaluate clinical consequences.