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RAVE Study: switch to tenofovir or abacavir from AZT or d4T
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Reported by Jules Levin
...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 HAART". 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
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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.
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% 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
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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.
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% 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
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