Progression of lipodystrophy (LD) with continued thymidine analogue usage: long-term follow-up from a randomized clinical trial (the PIILR study).
OBJECTIVE
During the 24-week PIILR study of protease inhibitor (PI) withdrawal, improved lipids and reduction in intraabdominal visceral fat was seen, however, there was also a loss of subcutaneous limb fat in patients with HIV-lipodystrophy (LD). It was hypothesized that overall improvement in LD may require a longer period of time off PIs.


METHODS
Follow-up of patients randomized to stop or continue PI-based therapy for 24 weeks, in a multicenter study, was continued for up to 120 weeks. Biochemistry and lipid parameters were assessed every 3 months. DEXA and CT scans were performed annually. Limb fat, visceral adipose tissue, and the lipodystrophy case definition score (LCDS) were used as indicators of LD severity.


RESULTS
Forty-five male patients with baseline and week 120 body composition data were assessed. There were no significant changes in the limb fat or visceral adipose tissue (VAT) components of LD, with the exception of the LCDS (change from baseline +5.79, p < .001). Control of viral replication was maintained and lipid and glycemic parameters were unchanged over the 120-week follow-up. Linear regression analysis showed on-study usage of stavudine was independently and significantly correlated with both decreased limb fat mass and a higher LCDS.


CONCLUSIONS
Body composition or metabolic features of LD did not improve over 2 years of observation in patients remaining on predominantly PI-sparing therapy. LD was adversely influenced by continued stavudine use.
National Centre for HIV Epidemiology and Clinical Research, University of New South Wales, Sydney, Australia. amartin@nchecr.unsw.edu.au
Allison
A
Martin
Don
D
Smith
Andrew
A
Carr
Jennifer
J
Hoy
John
J
Chuah
Simon
S
Mallal
Matthew
M
Law
Mark
M
Clements
David A
DA
Cooper
D000005:Abdomen / Q000473:pathology; D015502:Absorptiometry, Photon; D000273:Adipose Tissue / Q000000981:diagnostic imaging / Q000473:pathology; D001315:Australia; D001823:Body Composition; D018791:CD4 Lymphocyte Count; D002784:Cholesterol / Q000097:blood; D008076:Cholesterol, HDL / Q000097:blood; D008078:Cholesterol, LDL / Q000097:blood; D004334:Drug Administration Schedule; D005260:Female; D015658:HIV Infections / Q000188:drug therapy*; D017320:HIV Protease Inhibitors / Q000008:administration & dosage* / Q000009:adverse effects* / Q000627:therapeutic use; D039682:HIV-Associated Lipodystrophy Syndrome / Q000139:chemically induced* / Q000000981:diagnostic imaging / Q000473:pathology; D006801:Humans; D007328:Insulin / Q000097:blood; D008297:Male; D008875:Middle Aged; D018119:Stavudine / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use; D014057:Tomography, X-Ray Computed; D014280:Triglycerides / Q000097:blood; D019562:Viral Load; D015215:Zidovudine / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use
D008076:Cholesterol, HDL; D008078:Cholesterol, LDL; D017320:HIV Protease Inhibitors; D007328:Insulin; D014280:Triglycerides; D015215:Zidovudine; D002784:Cholesterol; D018119:Stavudine