Antiretroviral therapy with or without protease inhibitors impairs postprandial TAG hydrolysis in HIV-infected men.
Mechanisms underlying the lipodystrophy syndrome associated with antiretroviral therapy (ART) for HIV infection are not completely understood. We investigated the effect of ART on blood lipid concentrations in the fasting state and after consumption of a meal containing [1-13C]palmitic acid in HIV-positive men receiving nucleoside reverse transcriptase inhibitors (NRTI, n 7), NRTI combined with protease inhibitors (PI; NRTIPI, n 6), in HIV-positive but therapy-naïve men (noART, n 5) and in HIV-seronegative men (controls, n 6). HIV-positive subjects had higher fasting TAG concentrations and resting energy expenditure than controls. Subjects receiving NRTIPI therapy had higher fasting NEFA concentrations than the other groups. There were no significant differences in postprandial lipid metabolism between noART subjects and controls. NRTI therapy impaired hydrolysis of meal-derived TAG, most evidently when combined with PI (the NRTIPI group). Accumulation of 13C-label in the NEFA fraction was not different between groups. In the NRTIPI group, fasting and postprandial NEFA concentrations were significantly higher than other groups. Postprandial glucose and insulin responses in HIV-positive subjects did not differ from controls. These findings suggest that ART dyslipidaemia is associated with impaired postprandial TAG clearance, which is exacerbated by NRTIPI therapy. If dyslipidaemia is to be minimised in ART, the specific adverse effects of particular combinations during the fed state should be considered.
Ware
Lisa J
LJ
Institute of Human Nutrition, Southampton General Hospital, UK.
Jackson
Akil G A
AG
Wootton
Stephen A
SA
Burdge
Graham C
GC
Morlese
John F
JF
Moyle
Graeme J
GJ
Jackson
Alan A
AA
Gazzard
Brian G
BG
D000328:Adult; D019380:Anti-HIV Agents / Q000009:adverse effects* / Q000627:therapeutic use; D023241:Antiretroviral Therapy, Highly Active / Q000009:adverse effects / Q000379:methods; D001786:Blood Glucose / Q000378:metabolism; D004734:Energy Metabolism / Q000187:drug effects; D015658:HIV Infections / Q000097:blood / Q000188:drug therapy*; D017320:HIV Protease Inhibitors / Q000009:adverse effects / Q000627:therapeutic use; D015497:HIV-1; D006801:Humans; D006868:Hydrolysis / Q000187:drug effects; D015228:Hypertriglyceridemia / Q000097:blood / Q000139:chemically induced*; D007328:Insulin / Q000097:blood; D008297:Male; D008875:Middle Aged; D010084:Oxidation-Reduction / Q000187:drug effects; D019518:Postprandial Period / Q000502:physiology; D018894:Reverse Transcriptase Inhibitors / Q000009:adverse effects / Q000627:therapeutic use; D014280:Triglycerides / Q000097:blood; D055815:Young Adult
D019380:Anti-HIV Agents; D001786:Blood Glucose; D017320:HIV Protease Inhibitors; D007328:Insulin; D018894:Reverse Transcriptase Inhibitors; D014280:Triglycerides