People living with HIV-1 (PLWH) often gain weight while taking antiretroviral therapy (ART), but it is unclear whether this weight gain is linked to negative metabolic or cardiovascular outcomes in the early stages of treatment (i.e., female, Black, or Hispanic). The study objectives were to compare metabolic and cardiovascular outcomes in PLWH at high risk of weight gain between those who gained more than or equal to 5% or less than 5% of their body weight or body mass index (BMI) within the first 6 months after starting ART and those who gained more than 5 percent. Treatment-naive adult female, Black, or Hispanic PLWH who initiated ART and had less than or equal to 1 weight or BMI measurement before and within 6 months of starting treatment were identified in a retrospective longitudinal study using Symphony Health, an ICON plc Company, IDV® electronic medical records (October 1, 2014-March 31, 2021). (landmark period). Variation between PLWH who gained more than or equal to 5% weight/BMI and those who gained less than 5% was taken into account by applying an inverse likelihood of treatment weighting. After the landmark period, weighted hazard ratios (HRs) were used to compare the timing of each event among cohorts. Baseline characteristics were similar in the 2 cohorts (mean age: ~48 years, ~59% female, ~49% Black, ~17% Hispanic), and the weighted more than or equal to 5% and less than 5% cohorts had 620 and 632 patients, respectively. Type 2 diabetes mellitus (T2DM; HR=2.19; P=0.044) was substantially more likely to be diagnosed in PLWH, who gained more than equal to 5% of their starting weight/BMI over the course of a mean 2-year follow-up. No other outcomes were significantly different in frequency across the research groups. A higher risk of type 2 diabetes, but not of other metabolic or cardiovascular outcomes, was observed among female, Black, and Hispanic PLWH who experienced a weight/BMI less than or equal to 5% within 6 months after ART initiation, despite the relatively short follow-up duration of 2 years. More research is needed with longer follow-up and specific ART regimens to understand how ART-related weight gain affects long-term clinical outcomes fully.