Final 192-Week Efficacy and Safety Results of the ADVANCE Trial, Comparing 3 First-line Antiretroviral Regimens

Abstract

Background ADVANCE compared three WHO-recommended first-line regimens, in antiretroviral-naïve participants with HIV. Methods This randomized, open-label, non-inferiority trial enrolled participants living with HIV with no antiretroviral exposure in the previous six months, to either tenofovir alafenamide(TAF)/emtricitabine (FTC)+dolutegravir(DTG) two tablets), tenofovir disoproxil fumarate (TDF)/FTC + DTG (two tablets), or fixed-dose combination TDF/FTC/efavirenz(EFV) (one tablet). We report final safety and efficacy data up to 192 weeks. Results Repeat consent from the original 351 participants randomised to each arm, was obtained from 230 (66%) TAF/FTC + DTG participants, 209 (60%) TDF/FTC + DTG participants, and 183 (52%) TDF/FTC/EFV participants. At 192 weeks, 213 (61%) of the original 351 participants in the TAF/FTC + DTG, 195 (56%) in the TDF/FTC + DTG, and 172 (49%) in the TDF/FTC/EFV arms had confirmed RNA < 50, with low virological failure in all groups, and no significant integrase inhibitor mutations in any arms. Mean weight gain was 8.9 kg [SD 7.1] in the TAF/FTC + DTG arm, 5.9 kg [7.1] in the TDF/FTC + DTG group, and 3.2 kg [8.1] in the TDF/FTC/EFV group at 192 weeks from baseline, and was greatest among women, those on TAF, and those with lower baseline CD4 counts. The weight trajectory slowed after week 96. There were very few clinical events, and minor laboratory changes and differences between arms after 96 weeks. There were no significant differences in treatment-emergent hypertension or pregnancy outcomes by arm. Interpretation High viral suppression was seen across arms, with no resistance to DTG. Weight gain continued but slowed after 96 weeks, with few clinical events or laboratory changes.

Blood pressure increases are associated with weight gain and not antiretroviral regimen or kidney function: a secondary analysis from the ADVANCE trial in South Africa

“…ADVANCE was a randomized, non‐inferiority phase‐3 trial done in Johannesburg, South Africa during which 1053 patients were enrolled from February 2017 through May 2018. Detailed methods and protocol, including sample size justification, are available, with the full 96‐ and 192‐week results also published [ 22 , 23 , 24 ]. In summary, participants aged 12 years or older with HIV and no antiretroviral exposure, and a creatinine clearance (Cockcroft–Gault formula) of more than 60 ml/minute (80 ml/minute if <19 years), received one of three regimens: coformulated TAF‐FTC (25–200 mg) and DTG (50 mg) as two tablets, or coformulated TDF‐FTC (300–200 mg) and DTG (50 mg) as two tablets, or coformulated TDF‐FTC and efavirenz (EFV, 600 mg) as one tablet, all administered daily.…”