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Stopping ARVs Tied to Weight Loss (EFV and TDF) Boosts Odds of Weight Gain on Integrase Drugs
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IDWeek 2023, October 11-15, 2023, Boston
Mark Mascolini
The Duke team believes their findings "support the hypothesis that the weight gain observed with switching to INSTI-containing regimen is driven by stopping medications associated with weight loss."
People switching antiretrovirals to regimens built on a second-generation integrase inhibitor (INSTI) had higher odds of a 5% or greater weight gain if switching from a combination containing efavirenz (EFV) or tenofovir disoproxil fumarate (TDF)-agents associated with weight loss [1]. This 763-person single-center study at Duke University in North Carolina found no weight impact of switching from a protease inhibitor (PI) or a first-generation INSTI (raltegravir or elvitegravir).
Researchers evaluating EFV in a prior study hypothesized that weight gain with second-generation INSTIs (dolutegravir and bictegravir) may be driven by switching from antiretrovirals linked to weight loss [2]. To test that hypothesis a Duke University team retrospectively analyzed a cohort of adults switching to a second-generation INSTI regimen from 2014 to 2021.
The investigators used multivariable logistic regression to identify factors tied to 5% or greater or 10% or greater weight change after the switch to a second-generation INSTI. Covariates in these models were age, sex, race, ethnicity, preswitch body mass index, and preswitch antiretroviral regimen.
The 763 people studied had a median age of 52 and 30% were women. Most participants were black (58%), while 34% were white and 4% Hispanic. Two thirds of the group (68%) had an undetectable viral load at the switch and a median preswitch weight of 84 kg (185 lb). The group gained a median 1.3 kg (2.9 lb), and 30% gained at least 5% of their preswitch weight. Postswitch regimens were bictegravir plus TAF in 32%, dolutegravir plus TAF in 8%, and other dolutegravir regimens in 60%.
Multivariable logistic regression linked four variables to 5% or greater weight gain and one variable to 10% or greater weight gain, at the following odds ratios (OR) (and 95% confidence intervals):
Linked to 5% or greater gain
- Switching from EFV/FTC/TDF (Atripla): OR 1.79 (1.07 to 3.03)
- Switching from elvitegravir/COBI /FTC/TDF (Stribild): OR 2.75 (1.39 to 5.46)
- Switching from any EFV regimen: OR 1.63 (1.14 to 2.32)
- Switching from any TDF regimen: OR 1.65 (1.18 to 2.23)
Linked to 10% or greater gain
- Switching from any EFV regimen: OR 1.70 (1.03 to 2.76)
Regimens that did not independently affect odds of gaining 5% or more body weight were elvitegravir/COBI /FTC/TAF, raltegravir/FTC/TDF, and regimens containing darunavir/ritonavir, atazanavir/ritonavir, or lopinavir/ritonavir.
People who traded EFV before for an INSTI gained 2.10 kg more than people not taking EFV. And people taking TDF before the switch added 1.13 kg more than others.
The Duke team believes their findings "support the hypothesis that the weight gain observed with switching to INSTI-containing regimen is driven by stopping medications associated with weight loss."
References
1. Cutshaw MK, Harding M, Davenport CA, Okeke NL. Determinants associated with weight gain among persons with HIV who switch to integrase strand transfer inhibitors (INSTI). IDWeek 2023, October 11-15, 2023, Boston.
2. Leonard MA, Cindi Z, Bradford Y, et al. Efavirenz pharmacogenetics and weight gain
following switch to integrase inhibitor-containing regimen. Clin Infect Dis. 2021;73:e2153. https://academic.oup.com/cid/article/73/7/e2153/5896036
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