In the ADVANCE trial, more patients taking first-line TAF/FTC+DTG developed clinical obesity compared to TDF/FTC+DTG and TDF/FTC/EFV. Common associations with obesity include type 2 diabetes, cardiovascular disease (CVD), and metabolic syndrome. This analysis aimed to quantify these risks using standard risk algorithms.
In ADVANCE, 1,053 treatment-naïve patients in South Africa (99% black, 59% female) were randomized to 96 weeks of TAF/FTC+DTG, TDF/FTC+DTG, or TDF/FTC/EFV. Weight, lipids, fasting glucose, and blood pressure (BP) were measured at baseline and week 48, and used to calculate 10-year risks of CVD and type 2 diabetes using the Framingham, QRISK, and QDIABETES equations. Participants were included in the analysis if they were between the age of 25-84 years and had complete laboratory data for all parameters in risk equations. Treatment emergent metabolic syndrome was calculated at week 48 using the International Diabetes Federation definition and differences between groups were tested using a two-sample test of proportions.
296 (TAF/FTC+DTG), 286 (TDF/FTC+DTG), and 306 (TDF/FTC/EFV) participants were included in this analysis at baseline. Vital signs and laboratory parameters were similar at baseline across all treatment arms, 82(9%) participants were being treated for hypertension, 12(1%) had diabetes, and 45(5%) had metabolic syndrome. Changes from baseline to week 48 are displayed in Table 1. The risk of developing diabetes was higher in TAF/FTC+DTG compared to TDF/FTC+DTG (p=0.0051). Statistically significant differences were shown in the risk of CVD (Framingham and QRISK) between TAF/FTC+DTG and TDF/FTC/EFV. Treatment-emergent metabolic syndrome was 8%(TDF/FTC+DTG), 6%(TDF/FTC+DTG) and 3%(TDF/FTC/EFV), with statistically significant differences between TAF/FTC+DTG and TDF/FTC/EFV (p=0.021).
Treatment with TAF/FTC+DTG led to greater rises in weight, lipids and glucose than TDF/FTC+DTG, with small predicted 10-year risks of CVD and diabetes. There are concerns that these tools may either over- or underestimate risks in HIV and African populations. Longer term studies, with clinical or reliable surrogate endpoints in local HIV-positive populations are needed to validate these risk assessment tools.