No Overall Impact on Rate of Weight Gain With Integrase Inhibitor-Containing Regimens in Antiretroviral-Naïve Adults

James E. Burns; Oliver Stirrup; Laura Waters; David Dunn; Richard Gilson; Sarah L. Pett


HIV Medicine. 2022;23(3):294-300. 

In This Article

Abstract and Introduction


Objectives: Integrase strand transfer inhibitors (INSTIs) are commonplace in modern antiretroviral therapy (ART). Increased weight gain with their use is increasingly scrutinized. We evaluated weight changes in treatment-naïve adults with HIV-1 attending a UK centre who started regimens including raltegravir or dolutegravir.

Methods: A retrospective cohort study of adults prescribed an INSTI between January 2015 and March 2020 were categorized as having started an ART regimen containing raltegravir, dolutegravir, a protease inhibitor or a nonnucleoside reverse transcriptase inhibitor. Individuals with one or more weight measurement ≤ 5 years both pre- and post-ART initiation, who started a three-drug regimen with ≥ 6 months duration and achieved virological suppression (< 50 copies/mL) within 6 months were included. A random effects model with linear slope pre- and post-ART was used, adjusting for age, gender, ethnicity, ART regimen, backbone and year of initiation.

Results: The cohort included 390 adults; 88.7% were male, 66.4% were of white ethnicity, their median age was 40 years, there was a median of six weight measurements, 2.2 years from diagnosis to ART initiation, 2.9 years from ART to the last weight measurement, and weight and body mass index at initiation were 75 kg and 24.1 kg/m2 respectively. Of these, 254 (65%) started an INSTI. The average pre-ART rate of weight gain was 0.44 kg/year [95% confidence interval (CI): 0.19–0.70], increasing to 0.88 kg/year (0.63–1.10, p = 0.04) after ART initiation. Our adjusted model found no evidence of an association between ART regimen and rate of weight gain.

Conclusions: Weight increased in the cohort both pre- and post-ART. We found no evidence of a higher rate of weight gain following ART initiation with an INSTI compared with other regimens.


Integrase strand transfer inhibitors (INSTIs) are one of the recommended third agents for initial antiretroviral therapy (ART) regimens.[1] Raltegravir (RAL) and dolutegravir (DTG) remain the most widely used INSTIs in the UK.[2] 'Excessive' weight gain with INSTI-based regimens has been reported in a variety of settings, although the magnitude of the weight gain impact attributable to INSTIs, and what level of change should be considered significant remains unclear.

In ART-naïve cohorts, weight gain after ART initiation is seen as part of a 'return-to-health' phenomenon, particularly in individuals with advanced immunosuppression. This is a manifestation of reduced immune activation and the associated high metabolic turnover following viral suppression.[3] By contrast, more recent cohorts are typically started on treatment earlier, and therefore weight change may be more reflective of an effect of the ART regimen and/or obesogenic environments that similarly influence the general population.

We conducted a retrospective analysis of an adult, ART-naïve HIV-1 cohort in London, UK, to evaluate the rate of weight change after starting a RAL- or DTG-containing regimen relative to other regimens.