Greater weight gain with INSTI-based than non-INSTI-based ART among women in US cohort
Polly Clayden, HIV i-Base
Switch to an integrase strand transfer inhibitor (INSTI) was associated with significant increases in body weight, body circumferences, and fat percentages compared to non-INSTI ART in women in the Women’s Interagency HIV Study (WIHS). 
There were no differences between observed changes in weight by INSTI(dolutegravir, elvitegravir, and raltegravir) but the numbers of women receiving each drug were quite small.
WIHS is a large, US-based, prospective cohort study, started in 1993, designed to investigate the progression of HIV in women.
Findings from the weight gain comparison were published in Clinical Infectious Diseases online 28 August 2019.
In this study, women enrolled in WIHS from 2006–2017 who switched to or added an INSTI to their regimen were compared to women on non-INSTI ART.
Body weight, body mass index (BMI), percentage body fat and waist, hip, arm, and thigh circumferences, were measured 6–12 months before and 6–18 months after INSTI switch/add with similar time points for the women on non-INSTI ART.
A total of 1118 women (234 INSTI and 884 non-INSTI) with a mean of two years follow up were included. The majority were African American (61%) their mean age was 49 years and weight at baseline was approximately 80 kg. There were no significant differences between the INSTI and non-INSTI groups.
Of the INSTI group: 42% (97) switched/added dolutegravir, 36% (85) raltegravir and 23% (52) elvitegravir.
All analyses were adjusted for baseline age, race, WIHS site, education, income, smoking status, and baseline ART regimen.
The INSTI group showed greater mean estimated increase compared with the non-INSTI group of 2.1 kg (2.4 vs 0.2 kg) in body weight (p<0.0001). The INSTI group had 0.8 kg/m2 greater mean increase in BMI, (p<0.0001) and 1.4% greater mean increase in percentage body fat (p<0.01).
There were also greater increases in waist, hip, arm, and thigh circumference in the INSTI group (all p <0.05).
There were no differences in the extent of these of these increases by INSTI type and the investigators wrote that they suspect this is a class effect.
In this study, nearly one-fifth of women receiving INSTIs gained clinically significant body weight.
It was conducted among women with a mean age of almost 50 years. During mid-life women gain approximately 0.7 kg per year and the investigators suggest that this may be compounded by additional 2 kg weight gain seen within 18 months in this study.
Women in the ADVANCE study (who were younger at a mean of 32 years at baseline) experienced the greatest mean increase in weight at 96 weeks (8 kg) when dolutegravir-based ART also included tenofovir alafenamide (TAF). 
In WIHS only 12% (29) women added TAF across all INSTI ART groups and the study did not look at differences by backbone antiretrovirals.
- Kerchberger AM et al. Weight gain associated with integrase strand transfer inhibitor use in women. Clinical Infectious Diseases. Published online 28 August 2019.
- Clayden P. Dolutegravir-based first-line non-inferior to efavirenz-based ART but associated with substantial weight gain: results from the ADVANCE study. HTB. 23 August 2019.