5th International Workshop on Adverse Drug Reactions and Lipodystrophy in HIV 8–11 July 2003, Le Meridien Montparnasse, Paris, France

EFFECTS OF HIV INFECTION, ANTIVIRAL TREATMENT AND BODY FAT CHANGES ON VLDL-APOLIPOPROTEIN-B METABOLISM

Antiviral Therapy 2003; 8:L6 (abstract 3)

S Das¹, M Stolinski², W Jefferson², N Jackson², G Gilleran¹, M O’Connor¹, R Cramb¹, M Umpleby² and M Shahmanesh^1
1University Hospital Birmingham NHS Trust, Birmingham, UK; and ²Guy’s Kings College and St Thomas’ Hospitals’ Schools of Medicine, London, UK

AIM: Lipid disorders are common in HIV patients. The underlying mechanism is not clear. We studied apolipoprotein B (apo-B) kinetics in HIV-negative controls and four HIV-positive groups.

METHODS: We performed a cross-sectional 9 h tracer kinetic study with ¹³C-leucine. Subjects were HIV-negative (control, n=15) and HIV-positive patients who were treatment-naïve (n=16) or taking highly active antiretroviral therapy containing a protease inhibitor (n=14), efavirenz (n=15) or nevirapine (n=12). The very low-density lipoprotein (VLDL) apo-B pool size, absolute secretion rate (ASR) and fractional catabolic rate (FCR) were compared between the groups by Mann–Whitney test.

RESULTS: Seventy-three subjects (53 male) mean age 39.4 ±11 years and body mass index 24.1 ±3.4 kg/m² were tested. Protease inhibitor-treated patients were older than the efavirenz group (P<0.05). CD4 counts were similar between HIV-positive groups. Baseline cholesterol was higher in the protease inhibitor and nevirapine group (ANOVA P=0.01) and triglycerides were similar in the different HIV groups. The VLDL apo-B ASR was lower in the controls (7.3 ±3.5 mg/kg/day), compared to the HIV treatment-naïve group (24.7 ±15.5, P=0.001). The FCR of the two groups were similar (13.0 ±5.8 vs 10.2 ±6.8 pools per day). Compared to the controls the FCR in the protease inhibitor, nevirapine and efavirenz groups were lower (6.6 ±3.2, P=0.004; 6.1 ±2.6, P=0.004; and 7.5 ±3.6, P=0.02, respectively). The ASR of controls was similar to the nevirapine (16.4 ±23.2, P=0.9) and efavirenz groups (29.6 ±30.6, P=0.8) but lower than the protease inhibitor group (25.2 ±19.2, P=0.02). The ASR between all the four HIV-positive groups were similar (P=0.1). Compared to the controls, VLDL apo-B pool size (61 ±50 mg) was larger in the HIV treatment-naïve group (259 ±278, P=0.002) and protease inhibitor group (474 ±470, P=0.02) but not the nevirapine (290 ±350) or efavirenz (335 ±351) groups.

CONCLUSIONS: HIV infection itself increases the absolute VLDL apo-B secretion from the liver. These are not increased further by treatment with a protease inhibitor, nevirapine or efavirenz containing antiviral regimens. VLDL apo-B catabolic rates are not effected by HIV infection but are reduced by antiviral treatment, regardless of highly active antiretroviral therapy treatment regimens. This provides a possible mechanism for the increase in plasma lipid levels in HIV patients after starting highly active antiretroviral therapy. Data for IDL will be presented at conference.

Presenting author: M Shahmanesh

2003-07-08
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