- A U.S. study monitored the impact on body size of switching HIV treatment around menopause
- Participants who switched to integrase inhibitors during menopause gained more weight
- However, those who made the switch before menopause were likely to avoid weight gain
HIV treatment (antiretroviral therapy; ART) is highly effective when used as directed. ART helps to reduce HIV production, eventually driving it to very low levels that cannot be measured with routinely used laboratory tests. These very low levels of HIV are commonly called “undetectable.” The suppression of HIV allows the immune system to largely repair itself. As a result, the risk of AIDS-related complications becomes extremely small.
What’s more, with good adherence to ART, researchers project that ART users will have a similar life expectancy to that of healthy people without HIV. Indeed, studies are finding that more ART users are living well into their senior years.
As the risk of AIDS has greatly diminished among many ART users, research is increasingly focused on issues related to aging. One of those issues is menopause.
Focus on integrase inhibitors
Integrase inhibitors are a class of HIV treatment. Clinical trials have found that they are generally well tolerated and highly effective when used in combination with at least one other anti-HIV drug.
Integrase inhibitors used in Canada today include the following:
- bictegravir (in Biktarvy)
- dolutegravir (in Dovato, Juluca, Triumeq, Tivicay)
- cabotegravir (in Cabenuva)
- raltegravir (Isentress)
In some clinical trials, researchers have found that the use of integrase inhibitors can cause weight gain, particularly in women and other people assigned female at birth such as transgender men and some non-binary people. Weight gain also tends to occur when going through menopause (regardless of HIV status). Emerging research from the University of California has found that the choice of ART and the timing of initiation may interact with menopause, in some cases intensifying weight gain.
Study details
A team of scientists at the University of California monitored two groups of cisgender women, as follows:
- 1,131 women with HIV, some of whom changed their regimen to one containing an integrase inhibitor
- 887 women who did not have HIV (and who did not take HIV medicines)
This work was a part of the Women’s Interagency HIV Study, which is a large, multi-decade observational study in the United States. The researchers focused on results from 2006 to 2019.
The research team looked at body composition changes by measuring the following:
- waist circumference
- body mass index (BMI)
The researchers observed how different factors (such as waist size, BMI and other assessments) changed over time. They then compared the results based on when in the menopausal transition the women switched to integrase inhibitors. They classified the women as being in pre-menopause, in early or late perimenopause (the transition to menopause) or in menopause itself. This was determined by blood tests.
The average profile of participants upon entering the study was as follows:
- age – late 40s
- BMI – 30 kg/m2 (indicates that obesity is very likely)
- CD4+ count – more than 600 cells/mm3
- viral load – 47% of participants had a suppressed viral load
- commonly used integrase inhibitors: dolutegravir – 38%; elvitegravir (in Genvoya and Stribild) – 32%; raltegravir – 21%; bictegravir – 9%
Phase matters
The main results of the study showed that women with HIV who switched to an integrase-inhibitor-based regimen later—particularly during or around menopause—were more likely to gain weight.
Waist circumference
When switching regimens before menopause, women with HIV did not gain more waist circumference than those without the virus. Whether or not they were on integrase inhibitors made little difference. This trend continued during the early stages of perimenopause.
However, if the move to integrase inhibitors happened in late perimenopause or during menopause, women on these drugs were likely to develop an increased waist circumference. This became particularly significant when a switch to integrase-inhibitor-based treatment occurred during menopause, with the effects peaking at around three and a half years into menopause.
Body mass index
While BMI increased in women with HIV during pre-menopause, there was no significant difference in those on integrase inhibitors and those not taking them. In early perimenopause, women on integrase inhibitors had higher BMI changes than women in the other groups.
Bear in mind
The results of the present study are not surprising, as other studies have shown an increase in weight across genders when starting integrase inhibitors, with people assigned female at birth being more greatly affected. In the present study, there was an average weight gain of about 2.4 kilograms for women on integrase inhibitors, while those not on integrase inhibitors gained closer to 0.2 kilograms. There were also indications that women older than 50 and in menopause who switched to an integrase inhibitor gained more weight than women in those categories who did not switch to an integrase inhibitor.
Note that the weight gain trend found in the study does not continue indefinitely. Researchers found that women who gained weight because they switched to an integrase inhibitor during late perimenopause eventually began to lose some of that weight about three years later. Exactly why they subsequently lost weight is not known. For instance, there was no information about whether these women began a program of dieting and exercise.
Why would weight gain occur?
The researchers are not certain why switching to an integrase inhibitor late in the menopause transition enhances the weight gain associated with this life change. It is plausible that integrase inhibitors might have some subtle effects on estrogen receptors on fat cells. This effect of these drugs could stimulate the growth, development and accumulation of fat cells. However, the potential impact of integrase inhibitors on fat cells and hormones is something that requires a separate study.
No impact of tenofovir or efavirenz
Older ART regimens that might lead to abnormal fat distribution (called lipoatrophy) may show different results, but the present study focused on women who were less likely to have used such treatments. The drugs that women were switching from—such as tenofovir alafenamide (TAF), tenofovir disoproxil fumarate (TDF) or efavirenz—did not make much difference in subsequent weight gain.
What to do?
This new research shows that switching to an integrase inhibitor during late perimenopause and menopause is likely to increase waist circumference and BMI in women. Therefore, the researchers recommend that women and their healthcare providers consider the menopausal phase when switching to an integrase inhibitor. Switching earlier may help reduce the risk of weight gain.
—Elna Schütz
Resources
Menopoz & you: A guide to menopause - CATIE
Not enough middle-aged Canadian women with HIV are talking about menopause with their doctors – CATIE News
REFERENCE:
Abelman RA, Ma Y, Mehta CC, et al. Switch to integrase strand transfer inhibitors during the menopausal transition is associated with accelerated body composition change in women with HIV. Clinical Infectious Diseases. 2024; in press.