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Limb Fat Increased by 25% 3 Years After Switch to TDF from d4T
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Reported by Jules Levin
ICAAC Sept 2007, Chicago
"The Safety and Efficacy of Switching Stavudine to Tenofovir DF in Combination with Lamivudine and Efavirenz in HIV-1-Infected Patients: 3-Year Follow-up After Switching Therapy"
J Madruga,1 I Cassetti,2 JM Suleiman,3 A Etzel,4 L Zhong,5 CB Holmes,5 A Cheng,5 and J Enejosa5 for the Study 903E Team
1Centro de Referência e Treinamento DST/AIDS, Sao Paulo, Brazil; 2Fundacion Centro Estudios Infectologicos, Buenos Aires, Argentina;
3Brasilmed Assistência Medica e Pesquisas, Sao Paulo, Brazil; 4Hospital Guilherme Alvaro, Santos, Brazil; and 5Gilead Sciences, Inc., Foster City, California
Author conclusions
- Three years after switching d4T to TDF
- Virologic suppression was maintained
- No patient experienced virologic failure
- Significant decreases in serum triglycerides and cholesterol were seen
- Significant improvement in limb fat was observed
- Small but clinically insignificant changes in estimated GFR were observed
- No changes in spine BMD and small but statistically significant decreases in hip BMD were seen
- No patient experienced pathologic fractures
Study 903 is a Phase III trial with an ongoing 336-week open-label extension phase and a completed 144-week randomized, double-blind phase designed to evaluate TDF compared to stavudine (d4T) in combination with 3TC and EFV in antiretroviral-naive patients.
METHODS
- Study 903 Main inclusion/exclusion criteria:
- HIV-infected patients naive to antiretroviral treatment, 18-65 years of age, with plasma HIV RNA > 5,000 copies/mL (c/mL)
- No significant laboratory or clinical abnormalities
- No CD4+ cell count criteria
- Patients in select sites (Argentina, Brazil, and Dominican Republic) rolled-over into a 336-week open-label extension phase (903E)
- Data obtained from patients participating in 903E who substituted d4T to TDF were analyzed. Patients patients rolled over into 903E.
RESULTS
Patient Disposition Through 3 Years After Switch
- 85 patients in the d4T arm substituted d4T to TDF
- 8 patients discontinued from the study prior to Year 3 (After Switch)
- 6 patients either withdrew consent, were non-compliant, lost to follow-up or other reason
- 1 patient discontinued due to abnormal renal function
- 1 patient discontinued due to pregnancy
- No patient experienced virologic failure
Figure 8. Median (Interquartile Range) Limb Fat (Kg) Prior to, and After Switch from Stavudine to Tenofovir DF
The graph shows mean limb fat after 96 weeks on d4T was 4.3 kg and at week 144 was 3.8 kg. After switching to TDF mean limb fat shows an incremental continuing increase to 4.1 kg* at week 192, 4.3 kg* at week 240, and 4.8 kg at week 288. (*p<0.0001 for change from time of switch). That equates approximately to a 25% increase in mean limb fat after 3 years post switch from d4T to TDF.
Figure 6. Mean (95% CI) Change from Double-Blind Baseline in Fasting SerumTriglyceride and Total Cholesterol Levels (mg/dL). From baseline levels at the beginning of study 903 both total cholesterol and triglycerides levels increased over the 3 years on d4T by 59 and 102 mg/dL, respectively. Three years after switching to TDF total cholesterol and triglycerides decreased to 41 and 38 mg/dL above baseline.
Figure 7. Mean (95% CI) Percent Change from Baseline in Bone Mineral Density of the Lumbar Spine and Hip. Hip BMD declined 0.6% after 144 weeks from baseline on d4T and after 3 additional years post switching to TDF hip BMD was -1.3% from baseline. Spine BMD declined 1.0% after 144 weeks on d4T and was -3.4% after 3 years post switching from TDF.
Bone Fractures
Through 3 years after switch, 1 patient experienced bone fracture which was trauma related and not considered related to TDF
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