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ZDV/3TC/LPV/r, but Not NVP/LPV/r, Is Associated with Limb Fat Loss and Relative Abdominal Fat Accumulation after 24 Months in ATT-naïve HIV-1-infected Men: MEDICLAS, a Randomized Clinical Trial
Marit GA van Vonderen*1, M van Agtmael1, E Hassink2, A Milinkovic3, K Brinkman4, S Geerlings5, M Ristola6, A van Eeden7, S Danner1, P Reiss5, and the MEDICLAS study group
1VU Univ Med Ctr, Amsterdam, The Netherlands; 2Intl Antiviral Therapy Evaluation Ctr, Amsterdam, The Netherlands; 3Hosp Clin, Barcelona, Spain; 4Onze Lieve Vrouwe Gasthuis, Amsterdam, the Netherlands; 5Academic Med Ctr, Univ of Amsterdam, The Netherlands; 6Helsinki Univ Central Hosp, Finland; and 7Medisch Centrum Jan van Goyen, Amsterdam, the Netherlands
Background: Lipoatrophy is associated with stavudine
(d4T) use, but less evidence exists whether this also applies to zidovudine (ZDV).
We prospectively evaluated body composition and metabolic changes in a
randomized multicenter trial comparing ZDV/lamivudine (3TC)-containing and
NRTI-sparing first-line ART.
Methods: ART-naïve men were randomized to
lopinavir/ritonavir (LPV/r, 400/100 mg twice daily)+ZDV/3TC or LPV/r (533/133 mg
twice daily)+nevirapine (NVP). Computed tomography, dual energy X-ray
absorptiometry (DEXA), and lipid profile were assessed before and after 3, 12,
24, and 36 months of ART. A mixed-model repeated-measures intent-to-treat final
analysis correcting for baseline was performed as planned after 24 months.
Results: Mean
baseline age was 42±10 years, body mass index 23.3±3.3 kg/m2, CD4
count 239±154 cells/mL, HIV-1 RNA 5±0.6 log10 copies/mL (comparable
between arms). In the ZDV/3TC/LPV/r arm, after 3 months limb fat decreased
progressively by 684±293 g until 24 months, whereas
abdominal fat increased exclusively in the visceral compartment. In contrast,
in the NVP/LPV/r arm, a generalized increase in fat mass was observed. After 24
months total and LDL cholesterol levels were higher in the NVP/LPV/r arm (6.1±0.2 vs 5.3±0.2 and 3.6±0.1 vs 2.8±0.1 mM/L, respectively) without
significant differences in HDL and total/HDL ratio.
Conclusions: ZDV/3TC/LPV/r, but not
NVP/LPV/r in ART-naïve patients, is associated with both lipoatrophy and relative abdominal lipohypertrophy,
suggesting that ZDV/3TC contributes to both these features of lipodystrophy.
NVP/LPV/r is associated with a worse lipid profile. Other ZDV/3TC sparing
initial treatment strategies are worth exploring.
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