JAC Advance Access originally published online on March 19, 2009
Journal of Antimicrobial Chemotherapy 2009 63(5):998-1005; doi:10.1093/jac/dkp071
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Original research |
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
1 Division of Infectious Diseases, University of Pennsylvania, Philadelphia, PA, USA 2 Harvard School of Public Health, Boston, MA, USA 3 DAIDS/NIAID/NIH, Bethesda, MD, USA 4 Miriam Hospital Immunology Center, Brown University, Providence, RI, USA 5 Department of Community Health and Family Medicine, Tufts University, Boston, MA, USA 6 Division of Endocrinology/Metabolism, Washington University in St Louis, St Louis, MO, USA 7 Division of Infectious Diseases, Northwestern University, Chicago, IL, USA 8 Frontier Science and Technology, Amherst, NY, USA
Received 20 October 2008; returned 30 November 2008; revised 3 February 2009; accepted 16 February 2009
* Corresponding author. E-mail: pablo.tebas{at}uphs.upenn.edu
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 
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
[ClinicalTrials.gov]
). 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.
Keywords: nucleoside reverse transcriptase inhibitors , thymidine analogues , stavudine , zidovudine , antiretroviral treatment
Deceased.