ADVANCE 96-week results: dolutegravir weight gain continues, especially in women and when used with TAF – no evidence of a plateau

Dolutegravir (DTG)-based regimens non-inferior to efavirenz (EFV)-based ART at week 96 in South African study but weight increase in the DTG arms continues, especially among women also receiving tenofovir alafenamide (TAF). These findings from ADVANCE were shown at AIDS 2020. [1]

ADVANCE is an ongoing three arm, 192 week, phase 3, study comparing first-line ART with: TAF/emtricitabine (FTC) + DTG, tenofovir disoproxil fumarate (TDF)/FTC + DTG or TDF/FTC/EFV.

Week 48 results were presented at IAS 2019 and published simultaneously in the NEJM. [2]

Participants were treatment naive and aged at least 12 years at baseline. Pregnant women and people coinfected with TB were excluded. There was no baseline genotyping, in accordance with South African ART guidelines.

A total of 1053 participants were randomised between February 2017 and May 2018: 99% black, 59% female, median age 32 years and CD4 count approximately 340 cells/mm³.

At week 96, the percentage of participants with viral load <50 copies/mL was 79% for TAF/FTC + DTG, 78% for TDF/FTC + DTG and 74% for TDF/FTC/EFV.

In men the mean change in weight at week 96 was +5.2 kg for TAF/FTC + DTG, +3.6 kg for TDF/FTC + DTG and +1.4 kg for TDF/FTC/EFV. Although there was incomplete data at this timepoint, at week 144, weight change was +7.2 kg, +5.5 kg and + 2.6 kg in the respective treatment arms.

In women the mean change in weight at week 96 was +8.2 kg for TAF/FTC + DTG, +4.6 kg for TDF/FTC + DTG and +3.4 kg for TDF/FTC/EFV. Again the data were incomplete but at week 144, weight change for women was +12.3 kg, + 7.4 kg and + 5.5 kg in the respective treatment arms.

Mass increases were largely fat over lean gain and were distributed between trunk and limbs in all arms. The gain in fat mass was significantly higher in women versus men, p<0.001.

At week 96, there was a statistically significant difference in treatment emergent metabolic syndrome between the TAF/FTC + DTG and TDF/FTC/EFV arms across all participants: 8.4% vs 3.9%, p=0.03. Almost 11% of women in the TAF/FTC + DTG arm experienced treatment emergent metabolic syndrome.

comments

Presenting author Simiso Sokhela suggested that these results from ADVANCE support current WHO ART guidelines, which reserve TAF/FTC + DTG only for people with osteoporosis or impaired renal function

It is concerning that weight continues to rise among people receiving DTG, particularly among women and those also receiving TAF, with no suggestion of a plateau. The study is now continuing until week 192, which will provide more information on this phenomenon.