title: Systematic review of antiretroviral-associated lipodystrophy: lipoatrophy, but not central fat gain, is an antiretroviral adverse drug reaction.
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.
authors.affiliation: Division of Clinical Pharmacology, Department of Medicine, University of Cape Town, Cape Town, South Africa. renee.dewaal@uct.ac.za
authors.forename: Reneé
authors.initials: R
authors.lastname: de Waal
authors.forename: Karen
authors.initials: K
authors.lastname: Cohen
authors.forename: Gary
authors.initials: G
authors.lastname: Maartens
mesh_terms: D015502:Absorptiometry, Photon; D050154:Adiposity / Q000187:drug effects*; D023241:Antiretroviral Therapy, Highly Active / Q000009:adverse effects*; D064420:Drug-Related Side Effects and Adverse Reactions; D017320:HIV Protease Inhibitors / Q000009:adverse effects; D006801:Humans; D050152:Intra-Abdominal Fat / Q000187:drug effects; D008060:Lipodystrophy / Q000139:chemically induced* / Q000000981:diagnostic imaging; D018894:Reverse Transcriptase Inhibitors / Q000009:adverse effects; D050151:Subcutaneous Fat / Q000187:drug effects; D014057:Tomography, X-Ray Computed; D060726:Torso
chemical_list: D017320:HIV Protease Inhibitors; D018894:Reverse Transcriptase Inhibitors