Under the terms of this licence, you may copy, redistribute and adapt the work for non-commercial purposes, provided the work is appropriately cited, as indicated below. In any use of this work, there should be no suggestion that WHO endorses any specific organization, products or services. The use of the WHO logo is not permitted. If you adapt the work, then you must license your work under the same or equivalent Creative Commons licence. If you create a translation of this work, you should add the following disclaimer along with the suggested citation: "This translation was not created by the World Health Organization (WHO). WHO is not responsible for the content or accuracy of this translation. The original English edition shall be the binding and authentic edition". Any mediation relating to disputes arising under the licence shall be conducted in accordance with the mediation rules of the World Intellectual Property Organization. Suggested citation. Update of recommendations on first-and second-line antiretroviral regimens. Geneva, Switzerland: World Health Organization; 2019 (WHO/CDS/HIV/19.15). Licence: CC BY-NC-SA 3.0 IGO.
With obesity on the rise among people living with HIV (PLWH), there is growing concern that weight gain may result as an undesired effect of antiretroviral therapy (ART). This analysis sought to assess the association between ART regimens and changes in body mass index (BMI) among ART-experienced, virologically suppressed PLWH. ART-experienced, virologically suppressed PLWH ‡18 years of age in the Observational Pharmacoepidemiology Research and Analysis (OPERA) cohort were included for analysis if prescribed a new regimen containing one of the following core agents: dolutegravir (DTG), elvitegravir/cobicistat (EVG/c), raltegravir (RAL), rilpivirine (RPV), or boosted darunavir (bDRV), for the first time between August 1, 2013 and December 31, 2017. Multivariable linear regression was used to assess the association between regimen and mean changes in BMI at 6, 12, and 24 months after switch. In unadjusted analyses, BMI increases ranged from 0.30 kg/m 2 (bDRV) to 0.83 kg/m 2 (RPV) at 24 months following switch, but gains were observed with every regimen. In adjusted analyses, compared to DTG, only bDRV was associated with a smaller increase in BMI at all time points, while EVG/c and RAL were associated with smaller increases in BMI at 6 months only. Overall, results were consistent in analyses stratified by baseline BMI category. BMI increases were relatively small but followed an upward trend over time in this cohort of treatment-experienced, suppressed PLWH. Gains were attenuated with a longer period of follow-up. BMI gains did not differ by regimens, except for bDRV regimens, which were consistently associated with smaller BMI increases than DTG.
BackgroundA potential association between integrase inhibitor (INSTI) use and weight gain has been reported in people living with HIV (PLWH). We examined body mass index (BMI) increases after a switch to dolutegravir (DTG), elvitegravir/cobicistat (EVG/c), raltegravir (RAL), rilpivirine (RPV), or boosted darunavir (bDRV) among virologically suppressed ART-experienced PLWH.MethodsART-experienced, suppressed (ART-ES; baseline viral load < 200 copies/mL) PLWH ≥ 18 years of age initiating DTG, EVG/c, RAL, RPV, or bDRV for the first time were identified in the OPERA® cohort. The association between core agents and mean increases in BMI at 6, 12, and 24 months was estimated with multivariable linear regression. Inverse probability-of-censoring weights (IPCW) were used to account for censoring (regimen discontinuation, loss to follow-up, death, pregnancy, or no BMI measured). Analyses were stratified by baseline BMI categories (underweight: <18.5, normal weight: ≥18.5 to <25, overweight: ≥25 to <30, obese: ≥30).ResultsAt baseline, endocrine disorders were reported in >40% of PLWH receiving DTG and RAL; >60% were overweight/obese in all groups (Figure 1). Mean BMI (unadjusted) increased for all ARVs over time, with changes at 24 months ranging from 0.30 (DRV) to 0.83 (RPV, Figure 2). At 6 months, the adjusted mean BMI increase was statistically smaller with EVG/c, RAL, and bDRV (range –0.15 to –0.30) than with DTG (Figure 3); these differences only remained significantly different for bDRV at 12 (–0.29) and 24 months (–0.29, Figure 3). Among those with a normal baseline BMI, the adjusted mean change in BMI at 12 months was smaller with EVG/c, bDRV, and RAL than DTG (range –0.26 to –0.27). Among overweight PLWH, the adjusted mean BMI increase was statistically smaller with bDRV than DTG (–0.32, Figure 4). Results were consistent in IPCW estimates.ConclusionThe majority of PLWH on stable ART in this US-based cohort were overweight/obese at the time of switch to the regimens of interest. Small mean increases in BMI for all regimens were noted over time, for which the clinical significance is not yet known. Apparent differences in BMI changes favoring EVG/c, RAL, and bDRV vs. DTG over the short term were largely attenuated with longer follow-up, with significant differences mainly observed in those with a normal BMI at baseline. Disclosures All Authors: No reported Disclosures.
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