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Dynamics of Weight Change After Initiation of Contemporaneous Antiretroviral Therapy in Treatment-Naive HIV-1 Infected Patients: Results From the Belgian HIV Cohort 2015-2021
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JAIDS June 1 2023
Van Praet, Jens T. MD, PhDa,b; Serrien, Ben PhDc; Ausselet, Nathalie MDd; Darcis, Gilles MD, PhDe; Demeester, Rémy MDf; De Munter, Paul MD, PhDg,h; De Scheerder, Marie-Angélique MD, PhDi; Goffard, Jean-Christophe MDj; Libois, Agnès MDk; Messiaen, Peter MD, PhDl,m; Yombi, Jean Cyr MDn; Van Beckhoven, Dominique MDc; on behalf of the Belgian HIV Cohort Study Group
To the Editors:

Weight gain has emerged as a novel side effect of contemporaneous antiretroviral therapy (ART) in people living with HIV (PLWH). Although it can be considered as a return to normal weight effect among ART-naive patients with low CD4 count, the extent of weight change is influenced by the composition of the initiated ART regimen.1,2 Both clinical trials and observational studies have documented associations of weight change after ART initiation with the use of integrase strand transfer inhibitors (INSTIs) and tenofovir alafenamide (TAF). Most data are available for the INSTIs dolutegravir (DTG), elvitegravir (EVG), and raltegravir (RAL), whereas weight change after bictegravir (BIC) initiation has been less well assessed in real-life setting. The effect of INSTIs on weight seems to be heterogeneous in nature and is more prevalent among women and patients of Black ethnicity.3 Furthermore, most of the weight gain occurs in the first 2 years after ART initiation,2 but the kinetics of weight gain have not been compared between different first-line single-tablet regimens. We therefore aimed to model the change in weight and body mass index (BMI) in a large consecutive group of treatment-naive adults with HIV after initiation of 3 contemporaneous first-line treatment options, including TAF/emtricitabine (FTC)/BIC.
Study Population and Data Collection

The population of interest were treatment-naïve adults with HIV in care in 10 Belgian HIV Reference Centers (HRC). Patients were eligible to be included if they were newly diagnosed with HIV-1 by a Belgian Aids Reference Laboratory (ARL) between January 1, 2015, and December 31, 2021, and started first-line ART maximally 1 year after the date of diagnosis (n = 1684). Reasons for exclusion were pregnancy (n = 40), not being prescribed a single-tablet regimen (n = 489), and less than 2 weight measurements available during the first 18 months of first-line ART (n = 182). Finally, we excluded 245 patients who were on a single-tablet regimen taken by less than 100 patients (see Figure 1, Supplemental Digital Content, https://links.lww.com/QAI/C27). The design and characteristics of the Belgian HIV cohort have been previously described4: individual-level data from PLWH in Belgium were collected through standardized data registries and managed by Sciensano, the Belgian Institute of Health. Sciensano is legally entitled to collect these data for HIV surveillance, approved by an independent administrative authority protecting privacy and personal data.5 This study was approved by the Ethical committee of AZ Sint Jan Brugge Oostende AV (advice number 2973).
Statistical Analyses
The outcomes of interest were the changes in weight and BMI over the course of the first 18 months after initiation of first-line ART. Follow-up ended if the patient was switched to a second-line ART before 18 months, ART was stopped, or the patient deceased.6 The following variables were included in the model as baseline covariates: age, sex, place of residence, nationality, ethnicity, height, probable mode of transmission, the presence of acute HIV infection at diagnosis, smoking, systolic blood pressure, CD4 count, plasma viral load, and the presence of an AIDS-defining illness/cancer at baseline. We considered the median taxable income of the patient's municipality as a proxy of his socioeconomic status because the individual taxable income was not available. All statistical analyses were performed in R 4.1.2 (R Core Team, 2021). Twenty-fold multilevel multiple imputation was performed to account for missing data.7 Multivariable linear mixed models were used to describe the kinetics of weight and BMI changes.6,8,9 Models were fitted on each imputed data set and pooled using the Rubin rule. A first sensitivity analysis was conducted where patients were excluded if they had an extreme high or low baseline weight/BMI (cutoff on 2.5 and 97.5 percentiles). A second sensitivity analysis was performed using plasma viral load as a time-varying covariate to control for potential differential adherence to the ART regimen. More details on statistical modeling can be found in Supplementary materials.
A total of 728 treatment-naive adults with HIV-1 were included in the analysis: 407 patients were prescribed FTC/TAF/BIC, 201 patients DTG/lamivudine(3TC)/abacavir (ABC), and 120 patients FTC/TAF/cobicistat-elvitegravir(cEVG). The overall and ART-specific patient characteristics and observed weight and BMI data are summarized in Table 1 and presented in Figure 2, Supplemental Digital Content, https://links.lww.com/QAI/C27.
Adjusted mean weight and BMI trajectories are shown in Figure 1, and slopes and contrasts between them are summarized in Table 2, Supplemental Digital Content, https://links.lww.com/QAI/C27. We used a piecewise linear change over time with a knot at 6 months after ART initiation. The slopes for all 3 ART regimens were positive in each period but decreased after 6 months. The slopes of weight and BMI gain were highest in FTC/TAF/BIC in each period, but a significant difference was observed only for DTG/3TC/ABC in the first 6 months (for weight gain, 0.72 kg/month (95% CI: 0.61 to 0.82) versus 0.49 kg per month (95% CI: 0.34 to 0.64)). No significant differences in weight or BMI gain between FTC/TAF/BIC and FTC/TAF/cEVG were found before and after 6 months of treatment. For FTC/TAF/cEVG, the increase in weight and BMI observed after 6 months was statistically nonsignificant.

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