Zidovudine/lamivudine but not nevirapine in combination with lopinavir/ritonavir decreases subcutaneous adipose tissue mitochondrial DNA

Eoin R. Feeney, Marit G. A. van Vonderen, Ferdinand Wit, Sven A. Danner, Michiel A. van Agtmael, Francesc Villarroya, Pere Domingo, Jacqueline Capeau, Peter Reiss, Patrick W. G. Mallon

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Objective: No randomized study has prospectively followed subcutaneous adipose tissue mitochondrial DNA (mtDNA) changes when starting thymidine nucleoside reverse transcriptase inhibitors (tNRTIs). Design: The Metabolic Effects of DIfferent CLasses of AntiretroviralS study randomized HIV-positive, treatment-naive male participants to start lopinavir/ritonavir (LPVr) with either zidovudine/lamivudine (ZDV/3TC) or nevirapine (NVP). Methods: Regional body fat was assessed by dual energy x-ray absorptiometry and abdominal computed tomography at months 0, 3, 12, 24 and 36. In a molecular substudy, subcutaneous adipose tissue (SAT) biopsies were taken, with mtDNA quantified by quantitative PCR. Data were analyzed using repeated measures linear regression analyses. Results: Of 50 participants recruited (23 to LPVr/ZDV/3TC), 48 started therapy, and 37 participants (19 on LPVr/ZDV/3TC) enrolled in the substudy. At 36 months, the LPVr/ZDV/3TC group had significantly lower limb fat [6.4 kg (0.26) versus 7.3 kg (0.31), P = 0.017] and a trend toward lower abdominal SAT compared to the LPVr/NVP group [131cm(2) (6.86) versus 146 cm(2) (6.33), P = 0.097]. Over 36 months, mtDNA declined in the LPVr/ZDV/3TC group [mtDNA region 1: -190 (95) copies/cell, P = 0.053, region 2: -269 (106) copies/cell, P = 0.016] but not within the LPVr/NVP group [region 1: +28 (99) copies/cell, P = 0.78, region 2: +51 (111) copies/cell, P = 0.65, between-group difference P <0.01 for both measurements]. mtDNA was significantly lower in the LPVr/ZDV/3TC group at 36 months. Conclusion: This is the first randomized study to prospectively demonstrate reductions in SAT mtDNA in patients initiating ZDV/3TC-containing antiretroviral therapy (ART) but not in those initiating nucleoside reverse transcriptase inhibitor-sparing ART containing NVP and protease inhibitor. That reductions in SAT mtDNA were also accompanied by lower limb fat suggests that use of ART not containing ZDV/3TC may help prevent development of peripheral lipoatrophy. (c) 2012 Wolters Kluwer Health vertical bar Lippincott Williams & Wilkins
Original languageEnglish
Pages (from-to)2165-2174
JournalAIDS (London, England)
Issue number17
Publication statusPublished - 2012

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