[P-09] The impact of tenofovir disoproxil fumarate on insulin sensitivity, adipocytokines and markers of endothelial function

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

6-8 November 2008, London, UK

THE IMPACT OF TENOFOVIR DISOPROXIL FUMARATE ON INSULIN SENSITIVITY, ADIPOCYTOKINES AND MARKERS OF ENDOTHELIAL FUNCTION

Antiviral Therapy 2008; 13(Suppl. 4):A29 (abstract no. P-09)

P Randell¹, A Jackson¹, L Zhong², K Yale² and G Moyle¹
¹Chelsea and Westminster Hospital, London, UK; ²Gilead Sciences, Foster City, CA, USA

OBJECTIVES: This study aimed to assess the impact of tenofovir disoproxil fumarate (TDF) on insulin sensitivity, selected adipocytokines and markers of endothelial function.

METHODS: This was a single-centre, randomized, double- blind, placebo-controlled study that used a two-sequence, two-period crossover design. HIV-negative males were recruited to the study and randomized 1:1 to receive either 2 weeks of TDF 300 mg once daily followed by 2 weeks of placebo or placebo initially followed by TDF. A hyperinsulinaemic euglycaemic clamp was performed at baseline, after 2 weeks and after 4 weeks (2 weeks after treatment switch).

RESULTS: In total, 16 participants completed all three clamps. Mean (±sd) insulin sensitivity (peripheral glucose disposal rate/mean insulin concentration [M/I] during the last hour of the clamp) was 15.4 (±4.64) at baseline, 16.2 (±4.32) after 2 weeks of TDF and 18.8 (±7.72) mg/kg/min per mU/l insulin ×100 after 2 weeks of placebo. There was no significant difference in M/I between groups or from baseline. In addition levels of adiponectin, leptin, plasminogen activator inhibitor-1, selectin P and selectin E were not significantly altered. No significant correlation between changes in adiponectin and leptin and changes in M/I was found. See Table 1.

Table 1. (Abstract P-09)

	Baseline (day 1 clamp)	After 2 weeks of TDF	After 2 weeks of placebo

Adiponectin (ng/ml)	4,647 (3,193–6,692)	5,603 (2,314–7,453.5)	5,521 (3,548.5–8,939)
Leptin (pg/ml)	3,398 (1,456–6,862)	4,497 (1,592–5,457)	3,312.5 (1,915–8,474)
PAI-1 (ng/ml)	4.25 (2.98–5.87)	4.68 (1.37–8.04)	4.35 (3.067–7.48)
Selectin P (ng/ml)	122.42 (103.05–163.46)	123.73 (104.50–161.28)	133.58 (125.14–162.98)
Selectin E (ng/ml)	35.67 (20.53–49.05)	34.19 (21.01–46.98)	33.77 (18.38–45.93)

Data are medians (interquartile range). n=16. PAI-1, plasminogen activator inhibitor-1; TDF, tenofovir disoproxil fumarate.

CONCLUSIONS: Two weeks of TDF did not have any significant impact on insulin sensitivity, assessed by the M/I ratio during euglycaemic clamp, adipocytokines or markers of endothelial function. These results support the view that TDF has minimal metabolic impact and would be suitable as backbone treatment in metabolic studies in HIV-positive patients.

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2008-11-06
P-09

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