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HIV and antiretroviral therapy-related fat alterations

Nature Reviews Disease Primers volume 6, Article number: 48 (2020) Cite this article

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An Author Correction to this article was published on 02 July 2020

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Abstract

Early in the HIV epidemic, lipodystrophy, characterized by subcutaneous fat loss (lipoatrophy), with or without central fat accumulation (lipohypertrophy), was recognized as a frequent condition among people living with HIV (PLWH) receiving combination antiretroviral therapy. The subsequent identification of thymidine analogue nucleoside reverse transcriptase inhibitors as the cause of lipoatrophy led to the development of newer antiretroviral agents; however, studies have demonstrated continued abnormalities in fat and/or lipid storage in PLWH treated with newer drugs (including integrase inhibitor-based regimens), with fat gain due to restoration to health in antiretroviral therapy-naive PLWH, which is compounded by the rising rates of obesity. The mechanisms of fat alterations in PLWH are complex, multifactorial and not fully understood, although they are known to result in part from the direct effects of HIV proteins and antiretroviral agents on adipocyte health, genetic factors, increased microbial translocation, changes in the adaptive immune milieu after infection, increased tissue inflammation and accelerated fibrosis. Management includes classical lifestyle alterations with a role for pharmacological therapies and surgery in some patients. Continued fat alterations in PLWH will have an important effect on lifespan, healthspan and quality of life as patients age worldwide, highlighting the need to investigate the critical uncertainties regarding pathophysiology, risk factors and management.

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Fig. 1: Effects of HIV on adipose tissue.
Fig. 2: Pathophysiological mechanisms involved in HIV-related and ART-related adipose tissue alterations and dysfunction.
Fig. 3: Alterations of immunity in adipose tissue from HIV-infected individuals with fat redistribution as compared with lean and obese non-infected individuals.
Fig. 4: Manifestations of ART-associated fat alterations.
Fig. 5: The ‘fourth 90’: proposed revision to the UNAIDS 90-90-90 targets.

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Change history

  • 02 July 2020

    An amendment to this paper has been published and can be accessed via a link at the top of the paper.

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Authors and Affiliations

  1. Division of Infectious Diseases, Vanderbilt University Medical Center, Nashville, TN, USA

    John R. Koethe

  2. Sorbonne Université, Faculty of Medicine, Inserm UMR_S938, Saint-Antoine Research Centre, FRM EQU201903007868, ICAN, RHU CARMMA, Paris, France

    Claire Lagathu & Jacqueline Capeau

  3. Department of Medicine, University of Texas Health Science Center at Houston, Houston, TX, USA

    Jordan E. Lake

  4. Department of Infectious Diseases, HIV Infection Unit, Hospital de la Santa Creu i Sant Pau, Barcelona, Spain

    Pere Domingo

  5. HIV/AIDS Unit and LIPO & Metabolism Group, Infectious Disease Division, Geneva University Hospitals, Geneva, Switzerland

    Alexandra Calmy

  6. Department of Medicine McGill University Health Center, Montreal, Québec, Canada

    Julian Falutz

  7. Division of Endocrinology, Diabetes, & Metabolism, Johns Hopkins University, Baltimore, MD, USA

    Todd T. Brown

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  8. Jacqueline Capeau
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Contributions

Introduction (J.C. and J.R.K.); Epidemiology (P.D., J.C. and J.E.L.); Mechanisms/pathophysiology (J.R.K. and C.L.); Diagnosis, screening and prevention (J.E.L.); Management (J.F.); Quality of life (A.C.); Outlook (T.T.B.); Overview of the primer (J.R.K. and J.C.). J.R.K. and C.L. contributed equally to the development of this Primer.

Corresponding author

Correspondence to Jacqueline Capeau.

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Competing interests

J.R.K. has received research support from Gilead Sciences and served as a consultant to Gilead Sciences and Theratechnologies. J.E.L. receives research support from Gilead Sciences and has served as a consultant to Gilead Sciences and Merck Sharp & Dohme. P.D. has received educational grants from and served as a consultant to Gilead Sciences, Johnson & Johnson, Merck Sharp & Dohme, and ViiV Healthcare. A.C. received unrestricted educational grants (to the institution) from BMS, Gilead, Merck Sharp & Dohme and ViiV Healthcare. J.F. has served on speakers’ bureaus from Gilead Sciences, Merck Sharp & Dohme and ViiV Healthcare, and has served as a consultant to Theratechnologies up to 2015. T.T.B. has served as a consultant to Gilead Sciences, Merck, Theratechnologies and ViiV Healthcare. J.C. has received research support (to the institution) from Janssen, Merck Sharp & Dohme and ViiV Healthcare, and educational grants from BMS, Gilead Sciences, Janssen, Merck Sharp & Dohme and ViiV Healthcare. C.L. declares no competing interests.

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Koethe, J.R., Lagathu, C., Lake, J.E. et al. HIV and antiretroviral therapy-related fat alterations. Nat Rev Dis Primers 6, 48 (2020). https://doi.org/10.1038/s41572-020-0181-1

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