Effects of boosted tipranavir and lopinavir on body composition, insulin sensitivity and adipocytokines in antiretroviral-naive adults.
OBJECTIVE
Thymidine-based nucleoside analogue reverse transcriptase inhibitors and some protease inhibitors of HIV are associated with lipoatrophy, relative central fat accumulation and insulin resistance. The latter associations have not been well evaluated prospectively in adults commencing antiretroviral therapy. We studied the effects of protease inhibitor-based antiretroviral regimens on body composition, insulin sensitivity and adipocytokine levels.


METHODS
48-week substudy of a randomized, open-label, three-arm trial.


METHODS
Hospital and community HIV clinics.


METHODS
140 HIV-infected adults naive to antiretroviral therapy.


METHODS
Tipranavir/ritonavir [500/200 mg twice a day (TPV/r200)] or [500/100 mg twice a day (TPV/r100)] or lopinavir/ritonavir [400/100 mg twice a day (LPV/r)], each with tenofovir + lamivudine.


METHODS
Body composition [dual-energy x-ray absorptiometry for limb fat; L4, abdominal computed tomography for visceral adipose tissue (VAT)]; and fasting metabolic parameters. The primary analysis was change in limb fat mass in each TPV/r group vs. LPV/r.


RESULTS
Limb fat increased in all three groups: LPV/r (1.17 kg) versus TPV/r200 (0.83 kg; P = 0.16) and TPV/r100 (0.41 kg; P = 0.07). VAT decreased in all groups: LPV/r (-3 cm) vs. TPV/r200 (-9 cm; P = 0.04) and TPV/r100 (-6 cm; P = 0.40). No significant change in insulin sensitivity was observed, including by oral glucose tolerance testing. The increase in leptin levels was significantly correlated with the increase in limb fat mass (r = 0.67; P < 0.0001). Despite increased limb fat, adiponectin levels increased, but significantly more with TPV/r200 (+6010 ng/ml; P < 0.0001) or TPV/r100 (+4497 ng/ml; P = 0.002) when compared with LPV/r (+1360 ng/ml).


CONCLUSIONS
Unlike many other antiretroviral regimens, TPV/r or LPV/r with tenofovir-lamivudine increased subcutaneous fat without evidence for increasing visceral fat or insulin resistance over 48 weeks.
Carr
Andrew
A
HIV, Immunology and Infectious Diseases Unit,, St Vincent's Hospital, Sydney, Australia. acarr@stvincents.com.au
Ritzhaupt
Armin
A
Zhang
Wei
W
Zajdenverg
Roberto
R
Workman
Cassy
C
Gatell
Jose M
JM
Cahn
Pedro
P
Chaves
Ricardo
R
D052242:Adiponectin / Q000378:metabolism; D000328:Adult; D001823:Body Composition / Q000187:drug effects*; D018791:CD4 Lymphocyte Count; D004334:Drug Administration Schedule; D004338:Drug Combinations; D005260:Female; D015658:HIV Infections / Q000150:complications / Q000188:drug therapy*; D017320:HIV Protease Inhibitors / Q000494:pharmacology / Q000627:therapeutic use; D015497:HIV-1 / Q000187:drug effects*; D039682:HIV-Associated Lipodystrophy Syndrome / Q000139:chemically induced* / Q000378:metabolism / Q000523:psychology; D006801:Humans; D007333:Insulin Resistance / Q000502:physiology; D061466:Lopinavir; D008297:Male; D011725:Pyridines / Q000494:pharmacology / Q000627:therapeutic use; D011744:Pyrimidinones / Q000494:pharmacology / Q000627:therapeutic use; D011753:Pyrones / Q000494:pharmacology / Q000627:therapeutic use; D019438:Ritonavir / Q000494:pharmacology / Q000627:therapeutic use; D013449:Sulfonamides
C499918:ADIPOQ protein, human; D052242:Adiponectin; D004338:Drug Combinations; D017320:HIV Protease Inhibitors; D011725:Pyridines; D011744:Pyrimidinones; D011753:Pyrones; D013449:Sulfonamides; D061466:Lopinavir; D019438:Ritonavir; C107201:tipranavir