10th International Workshop on Adverse Drug Reactions and Lipodystrophy in HIV


6-8 November 2008, London, UK

LIMB FAT CHANGES 48 WEEKS AFTER SWITCHING FROM AZT/3TC TO FTC/TDF VERSUS CONTINUING ON AZT/3TC. PRIMARY ENDPOINT ANALYSIS OF THE RECOMB TRIAL

Antiviral Therapy 2008; 13(Suppl. 4):A35 (abstract no. P-18)

E Martínez1, E Ribera2, B Clotet3, V Estrada4, J Sanz5, J Berenguer6, R Rubio7, F Pulido7, M Larrouse1, A Curran2, E Negredo3, S Arterburn8, P Ferrer9 and ML Alvarez9
1Hosp Clinic i Provincial, Barcelona, Spain; 2Hosp Vall D’Hebron, Barcelona, Spain; 3Hosp Germans Trias i Pujol, Barcelona, Spain; 4Hosp Clínico San Carlos, Madrid, Spain; 5Hosp La Princesa, Madrid, Spain; 6Hosp Gregorio Marañón, Madrid, Spain; 7Hosp 12 de Octubre, Madrid, Spain; 8Gilead Sciences Inc, Foster City, USA; 9Gilead Sciences SL, Madrid, Spain

OBJECTIVE: To compare changes in total limb fat, by dual energy X-ray absorptiometry (DEXA) scan assessment, after switching from an AZT/3TC backbone to FTC/TDF versus maintaining AZT/3TC.

METHODS: A 72 week, open-label, randomized, controlled study. Virologically-suppressed (<50 copies/ml) HIV-infected patients on highly active antiretroviral therapy (HAART) containing AZT/3TC (plus either a non-nucleoside reverse transcriptase inhibitor [NNRTI] or a protease inhibitor [PI]) were assigned to either switch their AZT/3TC backbone to FTC/TDF or continue on AZT/3TC. Stratification was performed by third agent of HAART (either NNRTI or PI). Post-hoc subanalyses were performed for total limb fat changes in patients by baseline (BL) limb fat, BL body mass index and prior duration of AZT/3TC therapy.

RESULTS: Eighty patients were included (39 FTC/TDF and 41 AZT/3TC). Mean age was 44 years. Patients were predominantly male (81%). Median baseline CD4 count was higher in the FTC/TDF versus AZT/3TC arm (655 versus 504 cells/mm3, P=0.037). In the FTC/TDF arm, one patient discontinued because of an adverse event (abdominal pain) and four patients in AZT/3TC group discontinued because of an adverse event (two cases of renal colic, one anaemia and one lactic acidosis). Mean change from BL to week 48 in estimated glomerular filtration rate (creatinine clearance by C-G) was -11.8 ml/min for FTC/TDF and -3.6 ml/min for AZT/3TC. See Table 1 and 2 for further results.
Table 1. Efficacy outcomes at week 48 (Abstract P-18)
Outcome FTC/TDF AZT/3TC P-value
Patients with HIV RNA <50 copies/ml, % (ITT M=F) 92 78 0.12
Median CD4 cell count change from BL, cells/mm3 60 9 NS
BL, baseline; M=F denotes missing=failure analysis; NS, not significant.
Table 2. Median change from BL in total limb fat (g) at week 48 by dual energy X-ray absorptiometry (Abstract P-18)
  FTC/TDF AZT/3TC  
BL Week 48 - BL BL Week 48 - BL P-value
Overall 3,565 +392 3,946 -257 0.001
Patients with BL limb fat ≤7.2 kg 3,138 +534 2,918 -259 <0.001
Patients with >5 years of prior AZT/3TC 2,964 +441 3,939 -204 0.003
Patients with BL BMI ≤25 kg/m2 3,311 +241 2,533 -241 0.011
Last observation carried forward for dual energy X-ray absorptiometry. BL, baseline; BMI, body mass index.

CONCLUSIONS: Through 48 weeks, switching from AZT/3TC to FTC/TDF was well tolerated, efficacy was maintained and significant improvements in overall limb fat content were observed. Switching to FTC/TDF significantly increased limb fat at week 48 compared with AZT/3TC for patients with BL limb fat content <7.2 kg, those with prolonged exposure to AZT and patients with BL body mass index ≤25 kg/m2.

2008-11-06
P-18

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