Effects of Tipranavir/ritonavir Compared to Lopinavir/ritonavir on Changes in Body Composition and Metabolic Parameters in Treatment-naive Patients

HIV and Hepatitis.com Coverage of the
4^th IAS Conference on HIV Pathogenesis, Treatment and Prevenion (IAS 2007)
July 22-25, 2007, Sydney, Australia

Although some data suggest that the incidence of body composition changes and other metabolic adverse effects are decreasing due to changes in treatment regimens, there is evidence that protease inhibitor (PI)-based antiretroviral therapy is associated with progressive lipoatrophy (fat loss), relative central fat accumulation, and insulin resistance.

In a poster exhibition at the 4th International AIDS Society Conference on HIV Pathogenesis, Treatment, and Prevention in Sydney, Australia (July 22-25, 2007), Dr. Andrew Carr presented data from a study evaluating changes in body composition and metabolism in 140 antiretroviral-naive patients randomized to receive tenofovir (Viread) plus 3TC (lamivudine, Epivir) plus tipranavir/ritonavir 500/200 mg or 500/100 mg twice daily OR lopinavir/ritonavir 400/100 mg twice daily in a metabolic sub-study.

At baseline and at 48 weeks, researchers assessed body composition (DEXA for total and regional fat; L4-5 abdominal CT scan for subcutaneous and visceral adipose tissue [SAT; VAT]), and metabolic parameters including blood lipids, glucose, insulin, adiponectin, and leptin.

The primary analysis was the change in limb fat in the tipranavir/ritonavir 100 mg and 200 mg arms vs. lopinavir/ritonavir.

Results

Baseline limb fat was higher in both tipranavir/ritonavir groups vs lopinavir/ritonavir, although medians were comparable.
At Week 48, limb fat increased more for lopinavir/ritonavir, but this was not significantly different from the tipranavir/ritonavir groups (P>0.07).
VAT and trunk fat decreased in all groups.
Adiponectin, but not leptin, increased substantially, but significantly more with tipranavir/ritonavir 100 mg and tipranavir/ritonavir 200 mg (P=0.002).
No glucose sensitivity changes were observed.

Parameter	TPV/r100		TPV/r200		LPV/r		p value
	Wk 0	Median change Wk 48	Wk 0	Median change Wk 48	Wk 0	Median change Wk 48	TPV/r 100 mg vs LPV	TPV/r 200 mg vs LPV
Limb fat (kg)	5.9	0.41	6.2	0.83	5.0	1.17	0.072	0.163
VAT (cm²)	72.1	-5.7	63.2	-8.6	70.8	-3.0	0.402	0.036
Adiponectin (ng/mL)	5962	4497	5347	6010	5920	1360	0.002	<0.0001
Leptin (pg/mL)	3037	-39	3855	608	2271	1168	0.015	0.324
Glucose (mg/dL)	88.6	0.0	89.0	0.9	84.0	3.8	0.320	0.355
Insulin (µU/mL)	5.6	-0.8	6.1	0.6	4.5	-0.2	0.149	0.317
HOMA-IR	1.3	-0.1	1.4	0.2	0.9	-0.1	0.150	0.684

TPV/r = tipranavir/ritonavir

LPV/r = lopinavir/ritonavir

Conclusion

The authors concluded, “After 48 weeks, subcutaneous fat increased with both tipranavir/ritonavir and lopinavir/ritonavir. Tipranavir/ritonavir treatment was not associated with increased insulin resistance or VAT, in contrast to previous studies with other PIs.”

St Vincent's Hospital, Sydney, Sydney, Australia, Projeto Praça Onze – UFRJ Hospital Escola São Francisco de Assis, Rio de Janeiro, Brazil, AIDS Research Initiative, Sydney, Australia, Hospital Clinic de Barcelona, Barcelona, Spain, Fundacion Huesped, Buenos Aires, Argentina, Boehringer Ingelheim GmbH, Biberach an der Riss, Germany,Boehringer Pharmaceuticals Inc, Ridgefield, United States.

08/03/07

Reference
A Carr, R Zajdenverg, C Workman, and others. Effects of tipranavir/ritonavir (500/200 or 500/100 mg BID) in comparison with lopinavir/ritonavir (400/100 mg BID) on changes in body composition and metabolic parameters in ARV-naïve patients over 48 weeks. 4th International AIDS Society Conference on HIV Pathogenesis, Treatment, and Prevention. Sydney, Australia, July 22-25, 2007. Abstract (poster) TuPeB072.

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