To evaluate the long-term risks of type 2 diabetes mellitus (T2DM) and cardiovascular disease secondary to weight gain and clinical obesity associated with the initiation of integrase strand transfer inhibitors (INSTIs) and tenofovir alafenamide (TAF) in the ADVANCE trial using validated risk equation tools.
Retrospective data analysis
In ADVANCE, 1,053 treatment-naïve participants in South Africa (99% black, 59% female) were randomized to 96 weeks of tenofovir alafenamide/ emtricitabine + dolutegravir (TAF/FTC+DTG), tenofovir disoproxil fumarate/ emtricitabine + dolutegravir (TDF/FTC+DTG), or tenofovir disoproxil fumarate/ emtricitabine + efavirenz (TDF/FTC/EFV). The 5- and 10-year risks of CVD were calculated using D:AD, QRISK and Framingham, and T2DM risk using QDiabetes, Cambridge Diabetes and Leicester Practice Risk scores. Participants were included in this analysis if they were above 30 years old at baseline.
217 (TAF/FTC+DTG), 218 (TDF/FTC+DTG), and 215 (TDF/FTC/EFV) participants had 96-week data available. Weight gain was +8.1 kg, +4.2 kg, and +2.4 kg on TAF/FTC+DTG, TDF/FTC+DTG, and TDF/FTC/EFV, respectively. Participants on TAF/FTC+DTG had greatest risk scores for CVD (using QRISK) and T2DM, driven by weight changes. Differences were statistically significant between TAF/FTC+DTG and TDF/FTC/EFV for CVD risk using the QRISK equation, equivalent to 1 extra case per 1,000 people treated over 10 years, and between all treatment groups for T2DM risk. Six extra T2DM cases were predicted on TAF/FTC+DTG vs TDF/FTC+DTG using QDiabetes.
Obesity, especially with TAF/FTC+DTG, drove increased risk of T2DM, with some evidence of greater CVD risk. However, predictive tools have not been validated in the HIV-positive and black African population