Weight gain among treatment-naïve persons with HIV starting integrase inhibitors compared to non-nucleoside reverse transcriptase inhibitors or protease inhibitors in a large observational cohort in the United States and Canada

Kassem Bourgi; Cathy A Jenkins; Peter F Rebeiro; Frank Palella; Richard D Moore; Keri N Altoff; John Gill; Charles S Rabkin; Stephen J Gange; Michael A Horberg; Joseph Margolick; Jun Li; Cherise Wong; Amanda Willig; Viviane D Lima; Heidi Crane; Jennifer Thorne; Michael Silverberg; Gregory Kirk; William C Mathews; Timothy R Sterling; Jordan Lake; John R Koethe; North American AIDS Cohort Collaboration on Research and Design (NA-ACCORD)

doi:10.1002/jia2.25484

Weight gain among treatment-naïve persons with HIV starting integrase inhibitors compared to non-nucleoside reverse transcriptase inhibitors or protease inhibitors in a large observational cohort in the United States and Canada

J Int AIDS Soc. 2020 Apr;23(4):e25484. doi: 10.1002/jia2.25484.

Authors

Kassem Bourgi^{1

2}, Cathy A Jenkins¹, Peter F Rebeiro¹, Frank Palella³, Richard D Moore⁴, Keri N Altoff⁴, John Gill⁵, Charles S Rabkin⁶, Stephen J Gange⁴, Michael A Horberg⁷, Joseph Margolick⁴, Jun Li⁸, Cherise Wong⁴, Amanda Willig⁹, Viviane D Lima¹⁰, Heidi Crane¹¹, Jennifer Thorne⁴, Michael Silverberg¹², Gregory Kirk⁴, William C Mathews¹³, Timothy R Sterling¹, Jordan Lake¹⁴, John R Koethe^{1

15}; North American AIDS Cohort Collaboration on Research and Design (NA-ACCORD)

Affiliations

¹ Vanderbilt University Medical Center, Nashville, TN, USA.
² Indiana University School of Medicine, Indianapolis, IN, USA.
³ Northwestern University Feinberg School of Medicine, Chicago, IL, USA.
⁴ Johns Hopkins University, Baltimore, MD, USA.
⁵ University of Calgary, Calgary, AB, Canada.
⁶ National Cancer Institute, Bethesda, MD, USA.
⁷ Mid-Atlantic Permanente Research Institute, Kaiser Permanente Mid-Atlantic States, Rockville, MD, USA.
⁸ Centers for Disease Control and Prevention, Atlanta, GA, USA.
⁹ University of Alabama at Birmingham, Birmingham, AL, USA.
¹⁰ University of British Columbia, Vancouver, BC, Canada.
¹¹ University of Washington, Seattle, WA, USA.
¹² Kaiser Permanente Division of Research, Kaiser Permanente Northern California, Oakland, CA, USA.
¹³ University of California San Diego, San Diego, CA, USA.
¹⁴ University of Texas Health Science Center at Houston, Houston, TX, USA.
¹⁵ Veterans Affairs Tennessee Valley Healthcare System, Nashville, TN, USA.

Abstract

Introduction: Weight gain following antiretroviral therapy (ART) initiation is common, potentially predisposing some persons with HIV (PWH) to cardio-metabolic disease. We assessed relationships between ART drug class and weight change among treatment-naïve PWH initiating ART in the North American AIDS Cohort Collaboration on Research and Design (NA-ACCORD).

Methods: Adult, treatment-naïve PWH in NA-ACCORD initiating integrase strand transfer inhibitor (INSTI), protease inhibitor (PI) or non-nucleoside reverse-transcriptase inhibitor (NNRTI)-based ART on/after 1 January 2007 were followed through 31 December 2016. Multivariate linear mixed effects models estimated weight up to five years after ART initiation, adjusting for age, sex, race, cohort site, HIV acquisition mode, treatment year, and baseline weight, plasma HIV-1 RNA level and CD4⁺ cell count. Due to shorter follow-up for PWH receiving newer INSTI drugs, weights for specific INSTIs were estimated at two years. Secondary analyses using logistic regression and all covariates from primary analyses assessed factors associated with >10% weight gain at two and five years.

Results: Among 22,972 participants, 87% were male, and 41% were white. 49% started NNRTI-, 31% started PI- and 20% started INSTI-based regimens (1624 raltegravir (RAL), 2085 elvitegravir (EVG) and 929 dolutegravir (DTG)). PWH starting INSTI-based regimens had mean estimated five-year weight change of +5.9kg, compared to +3.7kg for NNRTI and +5.5kg for PI. Among PWH starting INSTI drugs, mean estimated two-year weight change was +7.2kg for DTG, +5.8kg for RAL and +4.1kg for EVG. Women, persons with lower baseline CD4⁺ cell counts, and those initiating INSTI-based regimens had higher odds of >10% body weight increase at two years (adjusted odds ratio = 1.37, 95% confidence interval: 1.20 to 1.56 vs. NNRTI).

Conclusions: PWH initiating INSTI-based regimens gained, on average, more weight compared to NNRTI-based regimens. This phenomenon may reflect heterogeneous effects of ART agents on body weight regulation that require further exploration.

Keywords: HIV; North America; integrase inhibitors; metabolic; obesity; weight gain.

Publication types

Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't
Research Support, U.S. Gov't, P.H.S.

MeSH terms

Adult
CD4 Lymphocyte Count
Canada
Cohort Studies
Female
HIV Infections / complications
HIV Infections / drug therapy*
HIV Integrase Inhibitors / adverse effects*
HIV Integrase Inhibitors / therapeutic use
HIV Protease Inhibitors / adverse effects*
HIV Protease Inhibitors / therapeutic use
Heterocyclic Compounds, 3-Ring / adverse effects*
Humans
Male
Middle Aged
Oxazines
Piperazines
Pyridones
Reverse Transcriptase Inhibitors / adverse effects*
Reverse Transcriptase Inhibitors / therapeutic use
United States
Weight Gain / drug effects*

Substances

HIV Integrase Inhibitors
HIV Protease Inhibitors
Heterocyclic Compounds, 3-Ring
Oxazines
Piperazines
Pyridones
Reverse Transcriptase Inhibitors
dolutegravir

Abstract

Publication types

MeSH terms

Substances

Grants and funding