Weight Change and Predictors of Weight Change Among Patients Initiated on Darunavir/Cobicistat/Emtricitabine/Tenofovir Alafenamide or Bictegravir/Emtricitabine/Tenofovir Alafenamide: A Real-World Retrospective Study

Abstract

Background: Recent evidence suggests that integrase strand transfer inhibitors are associated with greater weight gain than protease inhibitors in patients with human immunodeficiency virus (HIV-1). Objectives: To describe demographic and clinical characteristics of insured patients with HIV-1 in the United States initiating darunavir/​cobicistat/​emtricitabine/​tenofovir alafenamide (DRV/c/FTC/TAF) or bictegravir/FTC/TAF (BIC/FTC/TAF), assess the differences in weight and body mass index (BMI) change between cohorts up to one year after treatment initiation, and identify the predictors of weight gain associated with each treatment. Methods: The Symphony Health, IDV® database (July 17, 2017 - September 30, 2019) was used to identify treatment naïve or virologically suppressed stable switchers who initiated DRV/c/FTC/TAF or BIC/FTC/TAF (index date) on or after July 17, 2018, were ≥18 years of age on the index date, and had ≥12 months of continuous clinical activity pre-index (baseline period). To account for differences in baseline characteristics, inverse-probability of treatment weighting (IPTW) was used. Mean weight and BMI change from pre- to post-index measurements were compared between weighted cohorts at 3, 6, 9, and 12 months post-index using mean differences. Predictors of weight or BMI gain ≥5% were evaluated at last measurement, for each treatment cohort separately. Results: After IPTW, 452 and 497 patients were included in the DRV/c/FTC/TAF and BIC/FTC/TAF cohorts, respectively. Baseline characteristics were generally well-balanced (mean age=~50 years, female: ~30%), except for the type of antiretroviral therapy from which patients switched. Patients initiated on BIC/FTC/TAF experienced greater weight and BMI increases between the pre-index period and each measurement of the post-index period than patients initiated on DRV/c/FTC/TAF, although results were only statistically significant at 9 months post-index (weight: mean difference=2.50 kg, P=0.005; BMI: mean difference=0.66 kg/m², P=0.027). A common predictor of weight or BMI gain ≥5% among patients in both cohorts was female gender (DRV/c/FTC/TAF: odds ratio [OR]=5.92, P=0.014; BIC/FTC/TAF: OR=2.00, P<0.001). Conclusion: Patients in the BIC/FTC/TAF cohort experienced greater weight and BMI increases than patients in the DRV/c/FTC/TAF cohort, with differences reaching statistical significance at 9 months post-index. Weight gain is an important factor to consider when selecting antiretroviral regimens, since it is associated with long-term health consequences. Future studies with larger sample size and longer follow-up time are warranted.

Keywords: body mass index; electronic health records; hiv; integrase inhibitors; observational study; protease inhibitors; weight gain.

Figure 1.. Identification of the Study Population

Abbreviations: BIC, bictegravir; BMI, body mass index; c, cobicistat; DRV, darunavir; FTC, emtricitabine; HIV-1, human immunodeficiency virus; ICD-9/10-CM, International Classification of Disease, Ninth/Tenth Revision, Clinical Modification; TAF, tenofovir alafenamide. ^aDate of approval for DRV/c/FTC/TAF as a single-tablet regimen. ^bPatients who initiated DRV/c/FTC/TAF and BIC/FTC/TAF were included in both cohorts. ^cPatients who initiate DRV/c/FTC/TAF and have ≥1 viral load test results ≥50 copies/mL during the 6-month period prior to index date. Patients who initiate BIC/ FTC/TAF and have ≥1 viral load test results ≥50 copies/mL during the 3-month period prior to index date.

Figure 2.. Mean Change in Weight and BMI Between the Pre- and Post-index Periods

Abbreviations: BIC, bictegravir; BMI, body-mass index; c, cobicistat; CI, confidence interval; DRV, darunavir; FTC, emtricit- abine; MD, mean difference; SD, standard deviation; TAF, tenofovir alafenamide. *Indicates P-value<0.05.

Figure 3.. Proportions of Patients Having any, ≥5%, and ≥10% Weight or BMI Increases Between the Pre- and Post-index Periods

Abbreviations: BIC, bictegravir; BMI, body mass index; c, cobicistat; CI, confidence interval; DRV, darunavir; FTC, emtricitabine; OR, odds ratio; TAF, tenofovir alafenamide. *Indicates P-value<0.05. †Indicates that the right bound of the 95% CI exceeds the range of the horizontal axis. ^aThe OR was not reported due to the small sample size and large number of covariates included in the model, which resulted in lack of model convergence.

Figure 4a.. Predictors of Weight or BMI Increase ≥5% Among Patients Initiating DRV/c/FTC/TAF

Abbreviations: BIC, bictegravir; BMI, body mass index; c, cobicistat; CCI, Charlson Comorbidity Index; CI, confidence interval; DRV, darunavir; FTC, emtricitabine; INSTI, integrase strand transfer inhibitor; OR, odds ratio; PI, protease inhibitor; TAF, tenofovir alafenamide; US, United States. *Indicates P-value<0.05. †Indicates that the right bound of the 95% CI exceeds the range of the horizontal axis.

Figure 4b.. Predictors of Weight or BMI Increase ≥5% Among Patients Initiating BIC/FTC/TAF

Abbreviations: BIC, bictegravir; BMI, body mass index; c, cobicistat; CCI, Charlson Comorbidity Index; CI, confidence interval; DRV, darunavir; FTC, emtricitabine; INSTI, integrase strand transfer inhibitor; OR, odds ratio; PI, protease inhibitor; TAF, tenofovir alafenamide; US, United States. *Indicates P-value<0.05. †Indicates that the right bound of the 95% CI exceeds the range of the horizontal axis.