Peripheral and visceral fat changes following a treatment switch to a non-thymidine analogue or a nucleoside-sparing regimen in HIV-infected subjects with peripheral lipoatrophy: results of ACTG A5110.
BACKGROUND
Switching a thymidine analogue to a non-thymidine analogue or changing to a nucleoside-sparing regimen has been shown to partially reverse peripheral lipoatrophy. The current study evaluated both approaches.


METHODS
Subjects at 15 AIDS Clinical Trial Group sites receiving thymidine analogue stavudine- or zidovudine-containing regimens with plasma HIV RNA < or =500 copies/mL and lipoatrophy were prospectively randomized to: (i) switch the thymidine analogue to abacavir; (ii) discontinue all antiretrovirals and switch to lopinavir/ritonavir plus nevirapine (LPV/r+NVP); or (iii) delay switching for 24 weeks (ClinicalTrials.gov identifier: NCT00028314). Single-slice computer tomography of mid-thigh and abdominal fat and metabolic and virological/immunological parameters were measured at baseline and weeks 24 and 48.


RESULTS
Among the 101 patients enrolled, there were significant subcutaneous thigh fat and subcutaneous abdominal tissue (SAT) increases over time and decreases in visceral adipose tissue to total adipose tissue (VAT:TAT) ratios for both interventions, and a decrease in VAT for abacavir. CD4 increased in the LPV/r+NVP arm. LPV/r+NVP had a significantly shorter time to grade 3 or higher toxicity (P = 0.007), but discontinuation rates were similar. Glucose levels did not change, but insulin decreased in the LPV/r+NVP arm. Lipids tended to increase in the LPV/r+NVP arm.


CONCLUSIONS
Switching stavudine or zidovudine to a non-thymidine analogue or changing to a nucleoside reverse transcriptase inhibitor-sparing regimen is associated with qualitatively similar improvements in thigh fat, SAT and VAT:TAT ratio at 48 weeks. Abacavir also resulted in VAT reductions and LPV/r+NVP resulted in CD4 count increases.
Tebas
P
P
University of Pennsylvania, Philadelphia, USA. pablo.tebas@uphs.upenn.edu
Zhang
J
J
Hafner
R
R
Tashima
K
K
Shevitz
A
A
Yarasheski
K
K
Berzins
B
B
Owens
S
S
Forand
J
J
Evans
S
S
Murphy
R
R
D019380:Anti-HIV Agents / Q000009:adverse effects* / Q000627:therapeutic use*; D018791:CD4 Lymphocyte Count; D015224:Dideoxynucleosides / Q000009:adverse effects / Q000627:therapeutic use; D005260:Female; D015658:HIV Infections / Q000150:complications / Q000188:drug therapy* / Q000276:immunology / Q000821:virology; D039682:HIV-Associated Lipodystrophy Syndrome / Q000139:chemically induced*; D006801:Humans; D050152:Intra-Abdominal Fat / Q000002:abnormalities*; D061466:Lopinavir; D008297:Male; D008875:Middle Aged; D019829:Nevirapine / Q000009:adverse effects / Q000627:therapeutic use; D011744:Pyrimidinones / Q000009:adverse effects / Q000627:therapeutic use; D011860:Radiography, Abdominal; D018119:Stavudine / Q000009:adverse effects / Q000627:therapeutic use; D013848:Thigh / Q000000981:diagnostic imaging; D019562:Viral Load; D015215:Zidovudine / Q000009:adverse effects / Q000627:therapeutic use; D000099227:Abacavir
D019380:Anti-HIV Agents; D015224:Dideoxynucleosides; D061466:Lopinavir; D019829:Nevirapine; D011744:Pyrimidinones; D018119:Stavudine; D015215:Zidovudine; D000099227:Abacavir