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October 3 -7, 2019
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BMI Jumps Slightly With Major Maintenance Regimens, Not Just Integrase Drugs
  IDWeek, October 2-6, 2019, Washington, DC
Mark Mascolini
Body mass index (BMI) rose through 24 months when people taking a suppressive regimen switched to an integrase inhibitor, a nonnucleoside (rilpivirine, RPV), or a boosted protease inhibitor (darunavir, bDRV), according to results of a 10,000-person US analysis [1]. BMI-change differences between regimens largely disappeared over 12 to 24 months of follow-up.
Previous research documented weight gains when people with HIV, especially women and blacks, start an integrase inhibitor regimen. To compare weight changes in people switching from a suppressive antiretroviral combination to one of five regimens (three integrase inhibitors, a nonnucleoside, or a boosted protease inhibitor), researchers analyzed 24 months of data from the US OPERA cohort.
OPERA includes more than 100,000 US residents in care for HIV infection in 65 cities, representing about 8% of the entire US in-care HIV population. Researchers prospectively capture routine clinical data from electronic health records of these people. This analysis focused on antiretroviral-experienced adults with an on-treatment viral load below 200 copies switching to a three-drug regimen between August 2013 and December 2017.
The new regimen could include one of three integrase inhibitors (dolutegravir [DTG], elvitegravir/cobicistat [EVG/c], raltegravir [RAL]), the nonnucleoside RPV, or the boosted protease inhibitor bDRV. Participants had to be starting these drugs for the first time. Everyone had a BMI measured when making the switch (or within the previous 3 months) and at least once 6, 12, and/or 24 months after the switch. Researchers estimated average 6-, 12-, and 24-month changes in BMI with multivariable linear regression adjusted for age, sex, race, tenofovir alafenamide (TAF) and other medications, and an array of other clinical and HIV variables.
The study group included 10,653 people, 35% switching to EVG/c, 33% to DTG, 18% to RPV, 9% to bDRV, and 5% to RAL. The proportion of people 50 or older was lowest for EVG/c (29%), followed by RPV (31%), bDRV (40%), DTG (42%), and RAL (54%). Proportions of women ranged from 13% with EVG/c to 21% with bDRV, and proportions of blacks from 30% with RAL to 42% with bDRV. More than half of the EVG/c group (56%) used TAF, compared with 39% on RPV, 14% on bDRV, 10% on DTG, and 5% on RAL.
At the antiretroviral switch, similar proportions across the 5 groups had normal BMI (34% to 38%) or were overweight (36% to 40%) or obese (22% to 26%). Among people with normal weight at the switch, about 20% in each of the 5 group became overweight after 12 months and fewer than 1% became obese. Among people overweight at the switch, 13% to 15% across groups became obese after 12 months.
Unadjusted analysis showed that average BMI rose with all five maintenance regimens 12 and 24 months after the switch. Gains proved somewhat higher with DTG, EVG/c, and RPV than with RAL or bDRV.
Six months after the antiretroviral switch, adjusted analysis determined that the average BMI increase was significantly smaller with EVG/c, RAL, and bDRV than with DTG, the comparator regimen. Twelve months after the switch, this smaller increase remained statistically significant with bDRV (-0.31, 95% confidence interval [CI] -0.49 to -0.12) but only approached statistical significance with EVG/c (-0.11, 95% CI -0.24 to 0.02) and RAL (-0.18, 95% CI -0.42 to 0.05). With RPV, the average 12-month change was virtually identical with that of DTG. After 24 months, the adjusted average BMI increase remained (barely) significantly smaller with bDRV than DTG (-0.29, 95% CI -0.57 to -0.01). But the 24-month changes with EVG/c and RAL had moved closer to the change with DTG.
Among people with normal weight at the switch, the 12-month adjusted difference in average BMI increase compared with DTG was significantly lower with EVG/c (-0.27, 95% CI -0.43 to -0.11) and bDRV (-0.26, 95% CI -0.50 to -0.03). But among people overweight at the switch, the difference from DTG was significant only for bDRV (-0.32, 95% CI -0.57 to -0.06).
Thus only people switching to the protease inhibitor bDRV had significantly lower increases in average BMI compared with DTG 6, 12, and 24 months after the switch overall, and 12 months after the switch among people with normal or overweight initial BMI. But normal-weight people switching to the integrase inhibitor EVG/c had a significantly lower increase in average BMI than people switching to DTG.
The OPERA team stressed that they saw only small absolute increases in BMI when switching to any of the five antiretrovirals assessed. They added that the clinical significance of these small gains remains unknown. Because the researchers recorded both weight gain and weight loss in all five antiretroviral groups, they suggested that "weight gain may be experienced by a subgroup of people living with HIV, not by all."
1. Mounzer K, Brunet L, Hsu R, et al. Changes in BMI associated with antiretroviral regimens in treatment-experienced, virologically suppressed individuals living with HIV. IDWeek, October 2-6, 2019, Washington, DC. Abstract 978.