title: Morphological and metabolic components of lipodystrophy in various nevirapine-based highly active antiretroviral therapy (HAART) regimens: a cross-sectional, observational study.
abstract: BACKGROUND
  Morphological abnormalities (lipoatrophy and central fat accumulation) and metabolic changes (dyslipidaemia and glucose regulation impairment) have emerged as components of lipodystrophy and as major tolerability issues with long-term use of highly active antiretroviral therapy (HAART) in HIV-positive patients. Protease inhibitors (PIs) are recognized as having the greatest impact in terms of metabolic complications, followed by nucleoside reverse transcriptase inhibitors, while the non-nucleoside reverse transcriptase inhibitors (NNRTIs) have the least impact. In particular, regimens based on the NNRTI nevirapine have been shown to achieve significant metabolic benefits and may help to improve dyslipidaemia. Improvements in body shape changes associated with lipodystrophy have also been reported when nevirapine replaced a PI in long-term triple therapy.
  
  
  OBJECTIVE
  The objective of this cross-sectional observational ('real-world') study was to investigate the effect of three HAART regimens plus stable nevirapine therapy on morphological and metabolic components of lipodystrophy in HIV-infected patients.
  
  
  METHODS
  Consecutive patients (aged >18 years) with serologically documented HIV infection, who had received HAART for at least 2 years and who had been diagnosed with lipodystrophy, were followed up as outpatients at the metabolic clinic of the University of Modena and Reggio Emilia, Modena, Italy. Patients received stable nevirapine therapy plus fixed-dose combinations of tenofovir disoproxil fumarate plus emtricitabine (Truvada(®); TVD), zidovudine plus lamivudine (3TC) [Combivir(®); CBV], or abacavir plus lamivudine (Kivexa(®); KVX). Multivariate regression analyses were performed to analyse predictors of four components of lipodystrophy: lipoatrophy using leg fat mass measured by dual-emission x-ray absorptiometry (DXA), fat accumulation using waist circumference, dyslipidaemia using apolipoprotein (Apo)B/ApoA1 ratio, and glucose intolerance using the Homeostasis Model Assessment for Insulin Resistance (HOMA-IR).
  
  
  RESULTS
  Overall, 101 patients were enrolled (TVD group = 61, CBV group = 20, KVX group = 20); 191 observations were analysed. Male sex was associated with reduced leg fat mass, while age and body mass index (BMI) were associated with increased leg fat mass (all p < 0.05). Leg fat mass and male sex were associated with increased waist circumference (p < 0.001 for both). Leg fat mass predicted reduced ApoB/ApoA1 ratio, while age and BMI predicted increased ApoB/ApoA1 ratio (all p < 0.05). BMI predicted HOMA-IR increase (p = 0.0017). No differences in lipoatrophy, central fat accumulation, dyslipidaemia or glucose metabolism were observed among any of the three different nevirapine plus nucleoside backbone groups (TVD, CBV or KVX).
  
  
  CONCLUSIONS
  HAART including nevirapine has a limited impact on components of lipodystrophy in patients with HIV infection. Further studies are needed to verify if nevirapine overcomes the expected distinct lipodystrophy risk profile associated with different nucleoside backbone therapies.
authors.affiliation: Clinica delle Malattie Infettive, Università degli Studi di Modena e Reggio Emilia, Modena, Italy. giovanni.guaraldi@unimore.it
authors.forename: Giovanni
authors.initials: G
authors.lastname: Guaraldi
authors.forename: Stefano
authors.initials: S
authors.lastname: Zona
authors.forename: Gabriella
authors.initials: G
authors.lastname: Orlando
authors.forename: Federica
authors.initials: F
authors.lastname: Carli
authors.forename: Chiara
authors.initials: C
authors.lastname: Stentarelli
authors.forename: Kety
authors.initials: K
authors.lastname: Luzi
authors.forename: Elisa
authors.initials: E
authors.lastname: Garlassi
authors.forename: Marianna
authors.initials: M
authors.lastname: Menozzi
authors.forename: Pietro
authors.initials: P
authors.lastname: Bagni
authors.forename: Fulvio
authors.initials: F
authors.lastname: Adorni
mesh_terms: D000328:Adult; D000368:Aged; D019380:Anti-HIV Agents / Q000009:adverse effects / Q000494:pharmacology / Q000627:therapeutic use*; D023241:Antiretroviral Therapy, Highly Active / Q000009:adverse effects; D001823:Body Composition / Q000187:drug effects; D050218:Body Fat Distribution; D003430:Cross-Sectional Studies; D004338:Drug Combinations; D050171:Dyslipidemias / Q000150:complications / Q000188:drug therapy / Q000378:metabolism / Q000473:pathology; D005260:Female; D015658:HIV Infections / Q000188:drug therapy* / Q000453:epidemiology / Q000378:metabolism; D015497:HIV-1 / Q000187:drug effects; D006801:Humans; D007333:Insulin Resistance / Q000502:physiology; D007558:Italy; D008060:Lipodystrophy / Q000188:drug therapy* / Q000453:epidemiology / Q000378:metabolism / Q000473:pathology; D008297:Male; D008875:Middle Aged; D019829:Nevirapine / Q000009:adverse effects / Q000494:pharmacology / Q000627:therapeutic use*; D010045:Outpatients; D011480:Protease Inhibitors / Q000009:adverse effects / Q000494:pharmacology / Q000627:therapeutic use; D018894:Reverse Transcriptase Inhibitors / Q000009:adverse effects / Q000494:pharmacology / Q000627:therapeutic use; D014495:Universities
chemical_list: D019380:Anti-HIV Agents; D004338:Drug Combinations; D011480:Protease Inhibitors; D018894:Reverse Transcriptase Inhibitors; D019829:Nevirapine