ADVANCE: 48-Week Data Support Dolutegravir-Containing ART Regimens

At week 48, 83.8% of participants in the TAF/FTC/DTG arm had HIV RNA < 50 copies/mL, 84.9% for TDF/FTC/DTG and 78.6% for TDF/FTC/EFV.

In many places around the world, including sub-Saharan Africa, efavirenz-containing antiretroviral therapy (ART) regimens are still considered first-line treatment, but more and more data supporting the use of dolutegravir continue to change the ART landscape.

Now, investigators on the ADVANCE study reported 48-week efficacy and safety data demonstrating that dolutegravir (DTG)-containing regimens performed as well as efavirenz (EFV)-containing regimens in South Africa. The findings were presented at the 10th IAS Conference on HIV Science (IAS 2019).

The 96-week, open-label, randomized trial compares ART regimens tenofovir alafenamide fumarate, emtricitabine, dolutegravir (TAF/FTC/DTG); tenofovir disoproxil fumarate, emtricitabine, dolutegravir (TDF/FTC/DTG); and tenofovir disoproxil fumarate, emtricitabine, efavirenz (TDF/FTC/EFV) in treatment-naïve people living with HIV (PLWH).

Enrolled participants were 12 years of age or older, with no prior ART >30 days, creatinine clearance >60 mL/min (>80 mL/min if <19 years), and HIV-1 RNA >500 copies/mL. Exclusion criteria included pregnancy and tuberculosis.

The primary treatment failure end point was 48-week HIV-1 RNA >50 copies/mL, discontinuation, or missing data (Intent-to-treat population, non-inferiority margin -10%, significance level p = 0.017, adjusted for multiple comparisons).

Between February 2017 and May 2018, 1053 PLWH (99% black, 59% female, mean age 32 years, with mean CD4 336 cells/uL) were randomized to receive 1 of the 3 ART regimens. At week 48, 83.8% of participants in the TAF/FTC/DTG arm had HIV RNA < 50 copies/mL, 84.9% for TDF/FTC/DTG and 78.6% for TDF/FTC/EFV.

“In the on-treatment analysis, 96% of participants on TAF/FTC/DTG, 94% on TDF/FTC/DTG and 95% on TDF/FTC/EFV had HIV RNA < 50 copies/mL at week 48,” investigators reported.

Overall, both DTG arms demonstrated non-inferior efficacy versus the EFV arm. Seventy-four percent of treatment failures were from discontinuation, and clinical adverse events and laboratory abnormalities were similar between treatment arms.

“In the ADVANCE study, TAF/FTC/DTG and TDF/FTC/DTG demonstrated non-inferior efficacy versus TDF/FTC/EFV, with low rates of virologic failure in all 3 arms despite country-level background NRTI/NNRTI resistance,” investigators concluded. “There were more discontinuations for adverse events in the TDF/FTC/EFV arm.”

The study, “The ADVANCE trial: Phase 3, randomized comparison of TAF/FTC/DTG, TDF/FTC/DTG or TDF/FTC/EFV for first-line treatment of HIV-1 infection,” was presented Wednesday, July 24 2019, at IAS 2019 in Mexico City, Mexico.