Weight gain and metabolic syndrome with dolutegravir and TAF: results from the ADVANCE trial
Sixty per cent of the study participants have data available at week 96 in this new analysis, so the findings here are more robust than those presented at IAS 2019.
There is significantly more treatment-emergent metabolic syndrome in the TAF/FTC/DTG arm (9%), compared with the TDF/FTC/EFV arm (3%). Metabolic syndrome is a predictor of diabetes and atherosclerosis.
The sensitivity analysis, removing anyone with GI adverse events, is important as it has been claimed that weight rises faster on TAF because it is so well tolerated, so people feel better. But this did not change the results. The investigators do not yet have a good explanation for the greater rises in body weight on TAF.
Twenty seven per cent of women in ADVANCE developed clinical obesity by week 96 and there is no sign of a plateau in weight gain. The investigators are now calculating the potential effects of this weight gain on increased risks of NCDs. These results will be submitted to CROI.
In the QDIABETES algorithm, if weight rises by 10 kg, the risk of diabetes rises by 3 cases per 1000 people treated. Although this does not sound much, in countries like South Africa where millions of people need ART, the absolute numbers could be substantial and create a huge extra burden on health services.
One of the ADVANCE investigators, Andrew Hill, gave an excellent overview of weight gain and clinical obesity with new treatments looking at these issues in more detail.  This is a recommended webcast (and will be summarised in the next issue of HTB).
Polly Clayden is on the scientific committee of ADVANCE and co-author of the NEJM paper.
- McCann K et al. The ADVANCE clinical trial: changes from baseline to week 96 in DXA-assessed body composition in TAF/FTC+DTG compared to TDF/FTC+DTG, and TDF/FTC/EFV. 17th European AIDS Conference (EACS). Basel, Switzerland. 6–9 November, 2019. Oral abstract PS3/3.
- Venter WDF et al. The ADVANCE trial: Phase 3, randomised comparison of TAF/FTC/DTG, TDF/FTC/DTG or TDF/FTC/EFV for first-line treatment of HIV-1 infection.10th IAS Conference on HIV Science. Mexico City, Mexico. 21–24 July 2019. Oral abstract WEAB0405LB.
- Venter WDF et al. Dolutegravir plus two different prodrugs of tenofovir to treat HIV. New England Journal of Medicine. Online ahead of print. 24 July 2019.
- Clayden P. Dolutegravir-based first-line non-inferior to efavirenz-based ART but associated with substantial weight gain: results from the ADVANCE study. HTB. 23 August 2019.
- Hill A et al. Progressive rises in weight and clinical obesity for TAF/FTC/DTG and TDF/FTC/DTG versus TDF/FTC/EFV: ADVANCE and NAMSAL trials. 10th IAS Conference on HIV Science. Mexico City, Mexico. 21–24 July 2019. Oral abstract MOAX0102LB.
- Hill A. Are new antiretroviral treatments increasing the risks of clinical obesity? 17th European AIDS Conferenc (EACS). Basel, Switzerland. 6–9 November, 2019. Oral presentation ML1. http://resourcelibrary.eacs.cyim.com/mediatheque/media.aspx?mediaId=78021&playlistId=78022&channel=28172 (webcast)