NATAP: Improving Fat Loss-Switch to TDF/ABC from AZT/d4T

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RAVE Study: switch to tenofovir or abacavir from AZT or d4T

Reported by Jules Levin

12th CROI

Feb 22-25, 2005

Boston, MA

…..Tenofovir & abacavir similarly allowed for restoration of limb & subcutaneous fat over 48 weeks when switching from thymidine analogues AZT or d4T…..limb fat (arm fat + total leg fat) increased after 48 weeks by over 300 grams of fat: 393 in TDF arm & 316 in ABC arm, but difference was not significant… trunk fat & total fat also increased. Moyle said this gain amounts to about 12% gain back of lost peripheral fat.

Graeme Moyle reported these study results at the 12th CROI: “A Randomised, Open-Label Comparative Trial of Abacavir or Tenofovir DF as Replacement for a Thymidine Analogue in Persons with Lipoatrophy and Suppressed HIV RNA on HAARTâ€. I sent out a preliminary report yesterday on this study, here is a more comprehensive report of this interesting study.

Moyle offered this rationale for the study:

--Thymidine analogue therapy is associated with peripheral fat loss and lipoatrophy

--Treatment modification of thymidine analogue to abacavir is associated with gradual recovery of peripheral fat

--Neither Abacavir nor Tenofovir DF have been convincingly associated with peripheral fat loss in prospective studies in treatment naïve persons

MITOX Study; patients switched from AZT/d4T to abacavir

Thymidine analogue recipients (n=105) with moderate to severe lipoatrophy were randomized to ABC or TDF plus ART for 48 weeks.

Primary endpoint: Change in total limb fat mass (by DEXA) over 48 weeks

Secondary endpoints: Changes in lipid measurements, VAT (from CT), CD4 count, HIV RNA, BMD and body fat over 48 weeks; incidence of clinical events

Analyses performed using intention-to-treat approach; missing values imputed using LOCF.

BASELINE CHARACTERISTICS

87%-94% men. 84% white. Median age: 42. Nadir median CD4; 114 in TDF arm (n=52), 154 in ABC (n=53). Current CD4: 522 in TDF, 478 in ABC. Years on ART: 5.7 in TDF, 4.9 in ABC. Current PI-sparing regimen: 63% in TDF, 74^ in ABC.

Current thymidine analogue:

D4T: 77% in TDF, 59% in ABC

AZT: 23% in TDF, 41% in ABC

BASELINE MEDIAN BODY COMPOSITION

TDF ABC

Total body fat (kg) 11.1 10.6

Total limb fat (kg) 3.0 2.9

Trunk fat (kg) 7.1 6.8

VAT (cm3) 150 148

SAT (cm3) 87 81

TAT (cm3) 237 241

Weight (kg) 74 72

BASELINE MEDIAN METABOLICS

TDF ABC

Total chol (mmol/l) 5.6 5.3

HDL-C (mmol/l) 1.3 1.3

LDL-C (mmol/l) 3.3 3.0

Triglycerides (mmol/l) 2.0 1.7

Insulin (IU/l) 8.8 7.2

Fasting glucose (mmol/l) 5.1 5.2

Lactate (mmol/l) 1.5 1.3

PATIENT DISPOSITION THROUGH WEEK 48

6% in the TDF (3/52) & 15% (8/53) in the ABC discontinued the study: 2% in TDF (n=1) due to AE & 6% (n=3) in ABC due to AE. All discontinuations due to AEs in ABC group were due to hypersensitivity reaction, TDF related to discontinuation was secondary to diarrhea.

% PATIENTS <50 Copies/ml

TDF: 94% at baseline, 100% at week 48

ABC: 93% at baseline, 91% at week 48

Median CD4 counts were +44 in TDF & +10 in ABC, p=0.51