Systematic review of antiretroviral-associated lipodystrophy: lipoatrophy, but not central fat gain, is an antiretroviral adverse drug reaction

PLoS One. 2013 May 28;8(5):e63623. doi: 10.1371/journal.pone.0063623. Print 2013.

Abstract

Background: Lipoatrophy and/or central fat gain are observed frequently in patients on antiretroviral therapy (ART). Both are assumed to be antiretroviral adverse drug reactions.

Methods: We conducted a systematic review to determine whether fat loss or gain was more common in HIV-infected patients on ART than in uninfected controls; was associated with specific antiretrovirals; and would reverse after switching antiretrovirals.

Results: Twenty-seven studies met our inclusion criteria. One cohort study reported more lipoatrophy, less subcutaneous fat gain, but no difference in central fat gain in HIV-infected patients on ART than in controls. Randomised controlled trials (RCTs) showed more limb fat loss (or less fat gain) with the following regimens: stavudine (versus other nucleoside reverse transcriptase inhibitors (NRTIs)); efavirenz (versus protease inhibitors (PIs)); and NRTI-containing (versus NRTI-sparing). RCTs showed increased subcutaneous fat after switching to NRTI-sparing regimens or from stavudine/zidovudine to abacavir/tenofovir. There were no significant between-group differences in trunk and/or visceral fat gain in RCTs of various regimens, but results from efavirenz versus PI regimens were inconsistent. There was no significant between-group differences in central fat gain in RCTs switched to NRTI-sparing regimens, or from PI-containing regimens.

Conclusions: There is clear evidence of a causal relationship between NRTIs (especially thymidine analogues) and lipoatrophy, with concomitant PIs possibly having an ameliorating effect or efavirenz causing additive toxicity. By contrast, central fat gain appears to be a consequence of treating HIV infection, because it is not different from controls, is not linked to any antiretroviral class, and doesn't improve on switching.

Publication types

  • Meta-Analysis
  • Review
  • Systematic Review

MeSH terms

  • Absorptiometry, Photon
  • Adiposity / drug effects*
  • Antiretroviral Therapy, Highly Active / adverse effects*
  • Drug-Related Side Effects and Adverse Reactions
  • HIV Protease Inhibitors / adverse effects
  • Humans
  • Intra-Abdominal Fat / drug effects
  • Lipodystrophy / chemically induced*
  • Lipodystrophy / diagnostic imaging
  • Reverse Transcriptase Inhibitors / adverse effects
  • Subcutaneous Fat / drug effects
  • Tomography, X-Ray Computed
  • Torso

Substances

  • HIV Protease Inhibitors
  • Reverse Transcriptase Inhibitors

Grants and funding

These authors have no support or funding to report.