Concerns of increased metabolic dysfunction have been heightened for HIV patients on long-term antiretroviral therapy (ART). Among first-line ART agents, Tenofovir alafenamide (TAF) may entail a marked increase in weight compared to Tenofovir disoproxil fumarate (TDF). We retrospectively evaluated changes in weight and glucose regulation among 153 treament-naïve patients. Weight-gain was more pronounced after one year of treatment with TAF versus TDF (3.5 kg versus - 1 kg, P-value <
0.001). However, weight-gain was attenuated with longer follow-up, and no increase in glucose dysregulation was noted for TAF treatment. Attribution of increased metabolic risk to treatment with TAF remains questionable.