Sex and gender differences in weight gain associated with second-generation integrase strand transfer inhibitors: A...

Weight gain associated with antiretroviral therapy, particularly second-generation integrase strand transfer inhibitors (INSTIs), is an increasingly recognized concern. However, literature remains mixed regarding whether these effects differ by sex/gender. This scoping review aims to map the pattern, timing, severity and risk factors for weight gain among cis and trans women initiating or switching to second-generation INSTIs, such as dolutegravir, bictegravir or cabotegravir.

Four databases (EMBASE, MEDLINE, Web of Science and CINAHL) were searched for studies reporting on weight gain after initiating or switching to second-generation INSTIs in cis and trans women or mixed cohorts with data disaggregated by sex/gender between 2010 and 2024. Three reviewers independently conducted the screening, and two reviewers extracted data.

Forty articles were included. Most studies reported trends of increased and excessive weight gain in cis women compared to cis men taking dolutegravir or bictegravir-based regimens, although findings were inconsistent and the extent of weight gain varied. Weight gain was particularly pronounced among treatment-naive cis women, those of Black ethnicity or in African settings, and participants receiving dolutegravir in combination with tenofovir alafenamide. Studies on weight gain in cis women taking cabotegravir-based regimens and trans women on any regimen were scarce.

Second-generation INSTIs, especially dolutegravir, appear to be associated with greater average and excessive weight gain among cis women, although this effect varies by setting, regimen and clinical context. Further research, especially in diverse populations, is needed to explore underlying mechanisms, determine risk factors and evaluate these trends in newer antiretroviral medications.