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Markedly Diminished Lipolysis and Partial Restoration of Glucose Metabolism, without Changes in Fat Distribution after Extended Discontinuation of Protease Inhibitors in Severe Lipodystrophic Human Immunodeficient Virus-1-Infected Patients

International Antiviral Therapy Evaluation Center (M.v.d.V., J.M.A.L.) and Departments of Endocrinology and Metabolism (G.A., H.P.S.), Clinical Epidemiology and Biostatistics (G.J.W.), Academic Medical Center, University of Amsterdam, Amsterdam 1105 AZ, The Netherlands; Department of Endocrinology (J.A.R.), Leiden University Medical Center, Leiden 2300 RC, The Netherlands; and Department of Clinical Chemistry (M.T.A., E.E.), Laboratory of Endocrinology and Radiochemistry, Departments of Infectious Diseases (J.M.A.L., P.R.), Tropical Medicine and AIDS, Nuclear Medicine (B.L.F.v.E.-S.), and Radiology (C.v.K.), Academic Medical Center, University of Amsterdam, Amsterdam 1105 AZ, The Netherlands

Address all correspondence and requests for reprints to: Marc van der Valk, M.D., Ph.D. International Antiviral Therapy Evaluation Center, Academic Medical Center, T0–120, Meibergdreef 9, 1105 AZ, Amsterdam, The Netherlands. E-mail: m.vandervalk{at}amc.uva.nl.

Treatment for HIV-1 infection is often complicated by a lipodystrophy syndrome associated with insulin resistance and an elevated rate of lipolysis. In eight HIV-1 infected men with lipodystrophy syndrome, we studied the effects of replacement of protease inhibitor (PI) by abacavir on insulin sensitivity and lipolysis by hyperinsulinemic euglycemic clamp and on fat distribution assessed by dual-energy x-ray absorptiometry and computed tomography scan.

Glucose metabolism and lipolysis were assessed by tracer dilution employing [6,6-²H₂]glucose and [²H₅]glycerol, respectively. Data are expressed as mean ± SD or 95% confidence interval (CI), as appropriate.

There were no significant changes in fat distribution assessed by dual-energy x-ray absorptiometry and computed tomography scan at wk 36 and wk 96. The fasting total glucose production decreased from 16.1 ± 2.5 at study entry by 1.1 (range, –2.1 to –0.1) to 15.0 ± 1.5 µmol/kg·min after PI withdrawal at wk 36 (n = 8). In an analysis restricted to the patients on treatment at wk 96 (n = 6), the decrease was 0.9 (range, –2.1 to 0.3) µmol/kg·min. During insulin infusion, glucose oxidation (as percent of total glucose disposal) increased from 36.8 ± 12.7% by 11.0% (range, 1.3–20.8) to 47.9 ± 13.9% in the wk 36 analysis. In the analysis restricted to the patients on treatment at wk 96 (n = 6) the increase was 7.7 (–4.0 to 19.4)%. Fasting lipolysis decreased from 2.7 ± 0.6 µmol/kg·min by 0.9 (–1.6 to –0.2) to 1.8 ± 0.3 µmol/kg·min in the wk-96 analysis (n = 6).

The replacement of the studied PIs by abacavir in severe lipodystrophic HIV-1-infected patients results in a marked reduction of lipolysis. In contrast, fasting glucose production and insulin-stimulated glucose oxidation improve moderately, whereas insulin-stimulated glucose disposal and fat distribution do not change.

The reverse study was supported by a grant by Glaxo-Wellcome Netherlands.

Abbreviations: CI, Confidence interval; CT, computed tomography; DEXA, dual-energy x-ray absorptiometry; LD, lipodystrophy syndrome; NRTI, nucleoside reverse transcriptase inhibitor; PI, protease inhibitor; SAT, sc adipose tissue; TAT, total adipose tissue; VCO₂, CO₂ production; VO₂, oxygen consumption.

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