icon-    folder.gif   Conference Reports for NATAP  
  17th CROI
Conference on Retroviruses
and Opportunistic Infections
San Francisco CA
February 16-19, 2010
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Darunavir Monotherapy Increased Limb Fat - Fat Tissue Distribution Changes in HIV-infected Patients with Viral Suppression Treated with Darunavir/ritonavir (DRV/r) monotherapy versus 2 NRTIs + DRV/r in the MONOI-ANRS 136 Randomized Trial : Results at 48 weeks
  Reported by Jules Levin
17th CROI Feb 16-19 2010 SF
M.A. Valantin1,2, P. Flandre2, S. Kolta3, C. Duvivier4,5, M. Algarte Genin2, D. Ponscarme6, L. Slama7, L. Cuzin8, M. Bentata8 and C. Katlama1,2 1Pitié-Salpêtrière hospital, 2Inserm UMR-S 943 UMPC, 3Cochin Port-Royal hospital, 4Institut Pasteur, 5Necker Enfants Malades Hospital, 6St Louis hospital, 7Tenon hospital, 8Avicenne hospital.
In patients with long exposure to NRTI-containing regimen, switch to darunavir/r monotherapy regimen leads to an increase of the limb fat tissue with:
· a reduced number of patients developing lipoatrophy over 48 weeks (1.5% vs 11%).
· a gain of 340g (8.3%) of adipose tissue in the darunavir/r monotherapy arm contrasting with a decrease of 20g in the triple therapy arm even in patients receiving abacavir/lamivudine or tenofovir/emtricitabine. There is a significant difference in change of glucose in the darunavir/r monotherapy compared with the triple-drug therapy. The increase of trunk fat observed in both groups warrants further investigation. Additional data at week 96 are ongoing.

Background: MONOI-ANRS136 is an ongoing open-label, randomized trial comparing the efficacy of 2 nucleoside reverse transcriptase inhibitors and darunavir/ritonavir (NRTI + DRV/r) vs DRV/r monotherapy in patients with suppressed HIV viremia. The primary analysis at week 48 showed non-inferiority of DRV/r compared with 2 NRTI + DRV/r (94% vs 99%, per protocol (PP) population). Whether such single drug strategy could improve fat tissue distribution abnormalities, frequent in HIV-treated patients, is an important clinical issue to be addressed.
Methods: MONOI-ANRS136 included a DEXA sub-study to evaluate changes in body composition between baseline and week 48. Evolution of fat tissue distribution was analyzed as changes in limbs and trunk fat tissue (kg). Lipoatrophy was defined as a loss >20% in limb fat and lipohypertrophy as a gain >20% in trunk fat from baseline. Fisher's exact and Wilcoxon tests were used for group comparisons. All analyses were intent-to-treat.
Results: Overall 141 patients (67 in the 2 NRTI + DRV/r arm and 74 in the DRV/r arm) of the 225 patients randomized in MONOI had DEXA-scans data at baseline and week 48. There was no difference regarding baseline characteristics between the subgroup with DEXA-scans and the total study population. In the triple therapy arm, backbone NRTI combined to DRV/r was: 3TC 51%, TDF 49%, FTC 43%, ABC 23%, AZT 22%, and DDI 12%. Median (IQR) baseline values were not different within arms: age 45 years (39.5 to 52.4 years), duration of HIV infection 11.2 years (4.8 to 16.9 years), weight 70.0 kg (64 to 78 kg), trunk fat 9.4 kg (6.1 to 13.0 kg), limb fat 5.0 kg (3.2 to 8.3 kg). Median changes in limb fat were -0.02kg and +0.34kg in the 2 NRTI + DRV/r and DRV/r arm, respectively (P =0.011).
Lipoatrophy was observed at week 48 in 8 of 74 (11%) patients receiving 2 NRTI + DRV/r in contrast with 1 of 67 (1%) patient in the DRV/r arm (P =0.04).
In the 8 lipoatrophic patients, the NRTI backbone was: TDF/FTC (n = 4), AZT/3TC (n = 2), 3TC/ddI (n = 1), ABC/3TC (n = 1).
There was no difference between the two arms neither in the change of trunk fat tissue (+0.6 kg vs +0.73 kg, P =0.40) nor in the proportion of patients with lipohypertrophy (23% vs 27%, P =0.70).
Conclusions: Through 48 weeks, MONOI study shows that the switch to a DRV/r monotherapy leads to a significant gain in limb fat tissue contrasting with no change in the triple-drug arm. Despite a NRTI backbone, which included mainly non-thymidine analogues, lipoatrophy was more frequent (11%) in the triple-drug arm compared to the monotherapy arm (1%).