Switch to an integrase inhibitor leads to greater weight during and after the menopause

Switching to an integrase inhibitor around the time of the menopause was associated with accelerated weight gain in women with HIV when compared to pre-menopausal women with HIV, a retrospective cohort study has found.

The study, conducted in the United States, was presented last week at the Conference on Retroviruses and Opportunistic Infections (CROI 2024) in Denver by Dr Rebecca Abelman of University of California San Francisco.

In previously untreated people with HIV, weight gain after starting treatment with an integrase inhibitor tends to be greater than with other classes of drugs. Weight gain after starting antiretroviral treatment is normal but some antiretrovirals, notably efavirenz and tenofovir disoproxil, appear to suppress weight gain. Integrase inhibitors on the other hand, especially when combined with tenofovir alafenamide, are associated with the greatest weight gain and this phenomenon is most marked in women.

In people who are already taking antiretroviral treatment, the effect on weight of switching to an integrase inhibitor is less clear. Some studies show that women, especially Black women, tend to gain more weight after a switch than men. However, the components of the previous regimen appear to influence weight gain. Switching from efavirenz and tenofovir disoproxil, which may suppress weight gain, may lead to a greater increase in weight when they are replaced by an integrase inhibitor.

Menopause is accompanied by changes in body fat distribution and weight gain. The impact of changing antiretroviral treatment on weight around the time of the menopause is unknown. To investigate this question, Dr Abelman and colleagues compared weight changes during the perimenopause (the time leading up to the last menstrual period) and the post-menopause (time beginning after the last period) between women with HIV, depending on whether they had switched to an integrase inhibitor or not, and a demographically similar control group of women without HIV.

Participants were recruited from the Women’s Interagency HIV study (WIHS) and the Multicenter AIDS Cohort (MACS). Cohort members were eligible for inclusion in the analysis if they had been on antiretroviral treatment with suppressed viral load for at least two years and had no experience of prior integrase inhibitor treatment at the time their switch was recorded. The study followed participants between 2006 and 2019.

The study included 424 women with HIV who switched to an integrase inhibitor, 733 who did not, and a control group of 994 women without HIV. Approximately two-thirds of study participants were African-American.

Women who had switched to an integrase inhibitor were slightly older than women with HIV who did not switch or the control group (52 vs 49 vs 47 years) and more likely to have reached the menopause (47% vs 35% vs 27%).

The study compared two measures of body composition – waist circumference and body mass index – and how they changed over time in the three groups. Changes were also compared between women who were pre-menopausal, perimenopausal or had reached the menopause, as measured by levels of anti-Müllerian hormone.

The analysis of waist circumference changes showed that pre-menopausal women gained a similar amount of weight over time, regardless of whether they switched to an integrase inhibitor or not (+0.06cm per 6 months and 0.08cm per 6 months faster gain in waist circumference respectively compared to women without HIV).

But in late perimenopausal women, a switch to an integrase inhibitor was associated with significantly faster increases in waist circumference up until 41 months after switching (+0.96cm per 6 months faster than women without HIV) when compared to no switch (+0.14cm).

Women with HIV who switched to an integrase inhibitor experienced faster increases in body mass index: in pre-menopausal women until 26 months after switching, and in late perimenopausal women until 31 months after switching, but only the latter difference was statistically significant.

The study investigators concluded that whereas switching to an integrase inhibitor does not seem to accelerate weight gain before the menopause, it does speed up weight gain as women with HIV reach the menopause. Both waist circumference, which is a measure of visceral fat, and body mass index, which is a measure of total weight gain, increased more quickly in women who had reached the menopause. Stage of menopause seems to reinforce changes in body composition that take place after switching to an integrase inhibitor, and the study investigators say that menopausal status should be considered before switching to an integrase inhibitor.