title: Fat tissue distribution changes in HIV-infected patients treated with lopinavir/ritonavir. Results of the MONARK trial.
abstract: Given the decline in mortality among HIV-infected patients, it has become increasingly important to consider delayed disease-related and/or anti-HIV therapy-related adverse effects, such as lipodystrophy, when choosing initial therapy. Data from the MONARK trial allowed for comparison of the potential lipodystrophic effects of lopinavir/ritonavir (LPV/r) monotherapy with those of triple therapy with LPV/r plus zidovudine (ZDV) and lamivudine (3TC). This was a randomized, open-label, multinational study that included 136 antiretroviral-naive HIV-infected patients. A portion of study patients underwent evaluations of limb and trunk fat tissue by dual-energy x-ray absorptiometry at baseline and after 48 weeks of treatment (and 96 weeks in some patients). Sixty-three patients had paired absorptiometry data at baseline and week 48 (13 patients at week 96). At week 48, median change in limb fat was -63 g on LPV/r monotherapy versus -703 g on LPV/r + ZDV/3TC triple therapy (p=0.014). The proportion of patients with fat loss (>20% loss in limb fat) was significantly lower with LPV/r monotherapy (4.9% versus 27.3%; p=0.018). Changes in trunk fat did not differ significantly between treatments. Nonetheless, limb fat and trunk fat varied in the same direction with both treatments. The decrease in arm lean mass was also significantly less in patients receiving LPV/r monotherapy. Only treatment type emerged as a significant predictor of fat loss (odds ratio, 7.06; 95% CI, 1.11-78.69). These results suggest that LPV/r, and possibly other protease inhibitors, may not be the main contributor to lipoatrophy in HIV-infected patients receiving triple therapy.
authors.affiliation: Paris-Descartes University, Medicine Faculty, UPRES-EA 4058, Assistance Publique-Hôpitaux de Paris, Cochin Hospital, Paris, France.
authors.forename: Sami
authors.initials: S
authors.lastname: Kolta
authors.forename: Philippe
authors.initials: P
authors.lastname: Flandre
authors.forename: Philippe Ngo
authors.initials: PN
authors.lastname: Van
authors.forename: Isabelle
authors.initials: I
authors.lastname: Cohen-Codar
authors.forename: Marc-Antoine
authors.initials: MA
authors.lastname: Valantin
authors.forename: Claire
authors.initials: C
authors.lastname: Pintado
authors.forename: Philippe
authors.initials: P
authors.lastname: Morlat
authors.forename: Francois
authors.initials: F
authors.lastname: Boué
authors.forename: Richard
authors.initials: R
authors.lastname: Rode
authors.forename: Michael
authors.initials: M
authors.lastname: Norton
authors.forename: Brygida
authors.initials: B
authors.lastname: Knysz
authors.forename: Karine
authors.initials: K
authors.lastname: Briot
authors.forename: Christian
authors.initials: C
authors.lastname: Roux
authors.forename: Jean-François
authors.initials: JF
authors.lastname: Delfraissy
mesh_terms: D015502:Absorptiometry, Photon; D000328:Adult; D019380:Anti-HIV Agents / Q000008:administration & dosage / Q000009:adverse effects*; D050218:Body Fat Distribution; D015658:HIV Infections / Q000188:drug therapy*; D039682:HIV-Associated Lipodystrophy Syndrome / Q000139:chemically induced*; D006801:Humans; D019259:Lamivudine / Q000008:administration & dosage / Q000009:adverse effects; D061466:Lopinavir; D008297:Male; D008875:Middle Aged; D011744:Pyrimidinones / Q000008:administration & dosage / Q000009:adverse effects*; D019438:Ritonavir / Q000008:administration & dosage / Q000009:adverse effects*; D015215:Zidovudine / Q000008:administration & dosage / Q000009:adverse effects
chemical_list: D019380:Anti-HIV Agents; D011744:Pyrimidinones; D061466:Lopinavir; D019259:Lamivudine; D015215:Zidovudine; D019438:Ritonavir