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

Abstract

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.

Figure 1

Design of the study. Individuals were randomized to A1, B1, A2 or B2. The assumption was that the population of subjects that delayed switching would be similar at the time of their switch to the population of subjects that switched at randomization, so groups A2 and B2 would be added to A1 and B1 for the ‘combined design’ using the week 24 evaluations as their baseline evaluation for this analysis. w, week; D4T, stavudine; ZDV, zidovudine; ABC, abacavir.

Figure 2

Week 24 and 48 results in the combined arms. Changes are expressed as median and IQR % change from baseline. The P values refer to the within-arm changes. The grey P values refer to the abacavir arm and the black P values refer to the LPV/r+NVP arm. ABC, abacavir.

Figure 3

Median glucose and insulin in the combined group. *Significant within-arm change from baseline (P < 0.05). ^†Significant between-arm change difference (P < 0.05). ABC, abacavir.

Figure 4

Median lipid/lipoprotein parameters. There were modest increases in total cholesterol and non-HDL cholesterol in the LPV/r+NVP arm. Triglycerides (TGD) increased remarkably in the LPV/r+NVP arm. HDL levels increased slightly in both arms. *Significant within-arm change from baseline (P < 0.05). ^†Significant between-arm change difference (P < 0.05). ABC, abacavir.

Figure 5

Median mitochondrial RNA and DNA levels in PBMCs in both arms. *Significant within-arm change from baseline (P < 0.05). ABC, abacavir.