Association Between Weight Gain and the Incidence of Cardiometabolic Conditions Among People Living with HIV-1 at High Risk of Weight Gain Initiated on Antiretroviral Therapy

Abstract

Introduction: Antiretroviral therapy (ART) has been associated with weight gain in people living with HIV-1 (PLWH); however, limited research has assessed whether early weight gain post-ART initiation is associated with metabolic or cardiovascular outcomes among PLWH at high risk of weight gain (i.e., female, Black or Hispanic). This study aimed to evaluate the incidence of metabolic and cardiovascular outcomes between PLWH at high risk of weight gain following an observed ≥ 5% or < 5% weight/body mass index (BMI) gain within 6 months following ART initiation.

Methods: A retrospective longitudinal study using Symphony Health, an ICON plc Company, IDV® electronic medical records (October 1, 2014-March 31, 2021) identified adult female, Black, or Hispanic treatment-naïve PLWH who initiated ART and who had ≥ 1 weight or BMI measurement pre- and within 6 months post-treatment (landmark period). Inverse probability of treatment weighting was used to account for differences between PLWH who experienced ≥ 5% and < 5% weight/BMI gain. The time to each outcome was compared between cohorts using weighted hazard ratios (HRs) after the landmark period.

Results: Weighted ≥ 5% and < 5% cohorts included 620 and 632 patients, respectively; baseline characteristics were similar between the two cohorts (mean age: ~ 48 years, ~ 59% female, ~ 49% Black, ~ 17% Hispanic). During a mean 2-year follow-up, PLWH with ≥ 5% weight/BMI gain were significantly more likely to be diagnosed with type 2 diabetes mellitus (T2DM; HR = 2.19; p = 0.044). There were no significant differences in the incidence of any other outcomes between the study cohorts.

Conclusion: Despite a short 2-year follow-up, female, Black or Hispanic PLWH experiencing ≥ 5% weight/BMI increase within 6 months following ART initiation had an increased risk of T2DM, but not other metabolic or cardiovascular outcomes, likely due to the short follow-up period. Further research with longer follow-up and specific ART regimens is warranted to examine the impact of ART-related weight gain on long-term clinical outcomes.

Keywords: Antiretroviral therapy; Cardiovascular disease; HIV-1; Metabolic disease; Observational study; Weight gain.

Fig. 1

Study design. ART  antiretroviral therapy, BMI  body mass index, DHHS  Department of Health and Human Services, INSTI  integrase strand transfer inhibitor, NNRTI  non-nucleoside reverse transcriptase inhibitor, PI  protease inhibitor. ^aBaseline laboratory and weight/BMI values were obtained from the baseline period measurement prior to and closest to the index date. ^bAll weight/BMI values observed during the landmark period were assessed to determine whether there was a weight/BMI gain ≥ 5% relative to the baseline value

Fig. 2

Identification of the study population. ART antiretroviral therapy, BMI  body mass index, CKD  chronic kidney disease, EMR  electronic medical records, ESRD  end-stage renal disease, INSTI  integrase strand transfer inhibitor, NNRTI  non-nucleoside reverse transcriptase inhibitor, PI  protease inhibitor

Fig. 3

Incident cardiometabolic outcomes comparison. BMI  body mass index, CI  confidence interval, HR  hazard ratio, ICD-9-CM/ICD-10-CM  International Classification of Diseases, Ninth/Tenth Revision, Clinical Modification, PLWH  people living with HIV-1, PTPY  per thousand patient-years. *Significant at the 5% level. ^aOf note, the number of patients reported in this weighted population represents the sum of weights for the corresponding patients, rounded to the nearest integer. The proportions displayed were calculated prior to the rounding and may be slightly different than if they were calculated based on rounded numbers. ^bType 2 diabetes, hypertension, lipid disorders, lipodystrophy, metabolic syndrome, coronary artery disease, congestive heart failure, stroke/transient ischemic attack or myocardial infarction. ^cThe incidence of metabolic syndrome may have been underestimated in the current analysis, as it was identified solely based on ICD-9-CM/ICD-10-CM codes and information such as waist circumference was not available. ^dIt was not possible to evaluate the hazard ratio for these outcomes because there were no incident events for at least one cohort