ADVANCE Study: DTG + TAF/FTC vs DTG + TDF/FTC vs EFV/TDF/FTC in first-line

Venter WDF, N Engl J Med. 2019;381:803-15 ; Venter WDF, IAS 2019, WEAB0405LB ; Hill A, IAS 2019, MOAX0102LB

Type of ARV Trial
Head-to-head comparative trials for first line ART since 2006


  • Treatment with DTG combined with FTC and either of two tenofovir prodrugs (TAF and TDF) showed noninferior efficacy to treatment with the standard-care regimen of EFV/TDF/FTC
  • There was significantly more weight gain with the DTG-containing regimens, especially in combination with TAF, than with the standard-care regimen
  • The concern around the potential teratogenicity of DTG and a dearth of pregnancy safety data with TAF pose complex challenges for practitioners in low- and middle-income countries that rely on health systems with limited options, especially for women
  • The increased risk of weight gain with both DTG-containing regimens and the limited knowledge base regarding TAF in pregnancy need to be evaluated against improvements in side effect profile and adherence, slight reductions in time to virologic control, and effect on bone mineral density and renal function


* Patients aged 12-19 years randomized separately

Primary endpoint

  • Proportion of patients with HIV RNA < 50 c/mL at W48, ITT-E snapshot analysis ; non-inferiority of TFA/FTC if lower margin CI for the difference = - 10%, 80% power

Secondary endpoints

  • Viral load thresholds, CD4 count changes, adverse events, safety, DXA

Baseline characteristics and disposition

HIV RNA < 50 c/mL

HIV RNA < 50 c/mL according to subgroups, ITT-E snapshot

Outcome after HIV RNA > 50 c/mL at W48 and Resistance at virologic failure

Adverse events

DXA results at W48

Mean change in weight (kg)

  • Weight gain ≥ 10% was associated to DTG + TAF/FTC, high baseline HIV RNA, low baseline CD4, female gender and overweight at baseline

Body composition by DXA : mean change from baseline (kg)

New obesity at W96 (BMI ≥ 30 kg/m²)

  • Higher rate on DTG + TAF/FTC vs DTG + TDF + FTC vs EFV/TDF/FTC: 19% vs 8% vs 4% (p < 0.01)
  • Regression analysis: emergence of obesity associated to DTG + TAF/FTC, baseline CD4 and HIV RNA, baseline BMI (women predictive factor is BMI omitted)