AIDS (London, England) · 2012
Zidovudine/lamivudine but not nevirapine in combination with lopinavir/ritonavir decreases subcutaneous adipose tissue mitochondrial DNA.
СтатьяМногоцентровое исследованиеРандомизированное исследованиеПоддержка исследования: вне правительства СШАНазвание и аннотация: Перевод пока не подготовлен
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Feeney Eoin R, van Vonderen Marit G A, Wit Ferdinand, Danner Sven A, van Agtmael Michiel A, Villarroya Francesc, Domingo Pere, Capeau Jacqueline, Reiss Peter, Mallon Patrick W G, MEDICLAS, NECATT study groups
Аннотация
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 [131 cm (6.86) versus 146 cm (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.
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 [131 cm (6.86) versus 146 cm (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.
Предметные рубрики MeSH
Absorptiometry, PhotonAcquired Immunodeficiency SyndromeAdolescentAdultAgedAnti-HIV AgentsAtrophyCD4 Lymphocyte CountDNA, MitochondrialDrug CombinationsDrug Therapy, CombinationHIV SeropositivityHIV-1HIV-Associated Lipodystrophy SyndromeHumansLamivudineLopinavirMaleMiddle AgedNevirapineProspective StudiesRNA, ViralReverse Transcriptase InhibitorsRitonavirSubcutaneous FatTreatment OutcomeYoung AdultZidovudine