HIV protease inhibitor substitution in patients with lipodystrophy: a randomized, controlled, open-label, multicentre study.
BACKGROUND
Lipodystrophy, dyslipidaemia and insulin resistance often complicate protease inhibitor-containing antiretroviral therapy. The aims of this study were to determine if these are reversible with continued HIV suppression following protease inhibitor substitution.


METHODS
Eighty-one HIV protease inhibitor recipients (78 male; mean antiretroviral therapy, 55 months) with predominant peripheral lipoatrophy, HIV RNA < 400 copies/ml plasma for at least the preceding 6 months, and no prior abacavir, non-nucleoside analogue or adefovir therapy were randomized 3 : 2 to continue nucleoside analogues and substitute protease inhibitor(s) with abacavir, nevirapine, adefovir and hydroxyurea (n = 49) or to continue all therapy (n = 32) with an option to switch at week 24. The primary endpoints were total body fat and HIV RNA at week 24. Other assessments were regimen safety, regional body composition, metabolic parameters, quality of life, and CD4 T-lymphocyte counts to week 48.


RESULTS
There was a greater decline in total body fat in the switch group than in the continue group (-1.6 and -0.4 kg, respectively at week 24; P = 0.006). This comprised greater declines in limb and subcutaneous abdominal fat, and in intra-abdominal fat of patients with moderate or severe abdominal fat accumulation. Viral suppression was similar, despite 18 (37%) switch group patients ceasing at least one study drug by week 24 because of adverse events. Total cholesterol and triglycerides declined more in the switch group (both P < 0.002). High density lipoprotein cholesterol increased significantly in both groups at week 48 (P < 0.02). There was no change for any glycaemic parameter.


CONCLUSIONS
In predominantly lipoatrophic patients, switching from HIV protease inhibitor therapy lead to improved lipids and less intra-abdominal fat, but also to less peripheral fat, and had minimal effect on insulin resistance. Virological control in these heavily pretreated patients was unaffected, despite frequent switch drug cessations.
Carr
A
A
HIV, Immunology and Infectious Disease Clinical Services Unit, St. Vincent's Hospital, Sydney, Australia.
Hudson
J
J
Chuah
J
J
Mallal
S
S
Law
M
M
Hoy
J
J
Doong
N
N
French
M
M
Smith
D
D
Cooper
D A
DA
D000225:Adenine / Q000031:analogs & derivatives* / Q000627:therapeutic use; D019380:Anti-HIV Agents / Q000627:therapeutic use*; D023241:Antiretroviral Therapy, Highly Active; D001823:Body Composition; D002331:Carnitine / Q000627:therapeutic use; D015224:Dideoxynucleosides / Q000627:therapeutic use; D004334:Drug Administration Schedule; D005260:Female; D015658:HIV Infections / Q000188:drug therapy* / Q000276:immunology / Q000821:virology; D017320:HIV Protease Inhibitors / Q000009:adverse effects / Q000627:therapeutic use; D015497:HIV-1 / Q000502:physiology; D006801:Humans; D006918:Hydroxyurea / Q000627:therapeutic use; D007333:Insulin Resistance; D008060:Lipodystrophy / Q000139:chemically induced* / Q000188:drug therapy; D008297:Male; D008875:Middle Aged; D019829:Nevirapine / Q000627:therapeutic use; D063065:Organophosphonates; D011788:Quality of Life; D012367:RNA, Viral / Q000097:blood; D018894:Reverse Transcriptase Inhibitors / Q000627:therapeutic use*; D016896:Treatment Outcome; D000099227:Abacavir
D000225:Adenine; D019380:Anti-HIV Agents; D002331:Carnitine; D015224:Dideoxynucleosides; D017320:HIV Protease Inhibitors; D006918:Hydroxyurea; D019829:Nevirapine; D063065:Organophosphonates; D012367:RNA, Viral; D018894:Reverse Transcriptase Inhibitors; D000099227:Abacavir; C053001:adefovir