Document Detail


Zidovudine/lamivudine but not nevirapine in combination with lopinavir/ritonavir decreases subcutaneous adipose tissue mtDNA.
MedLine Citation:
PMID:  22874517     Owner:  NLM     Status:  Publisher    
Abstract/OtherAbstract:
OBJECTIVE:: No randomised study has prospectively followed subcutaneous adipose tissue mitochondrial DNA (mtDNA) changes when starting thymidine nucleoside reverse transcriptase inhibitors (tNRTI). DESIGN:: The MEDICLAS study randomised HIV+, treatment-naïve male subjects to start lopinavir/ritonavir (LPVr) with either zidovudine/lamivudine (AZT/3TC) or NVP. METHODS:: Regional body fat was assessed by DXA and abdominal CT at months 0, 3, 12, 24 and 36. In a molecular substudy, SAT biopsies were taken, with mtDNA quantified by quantitative PCR. Data was analysed using repeated measures linear regression analyses. RESULTS:: Of 50 subjects recruited (23 to LPVr/AZT/3TC) 48 started therapy, and 37 subjects (19 on LPVr/AZT/3TC) enrolled in the substudy. At 36 months, the LPVr/AZT/3TC group had significantly lower limb fat (6.4kg(0.26) versus 7.3kg(0.31), P = 0.017) and a trend towards 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/AZT/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/AZT/3TC group at 36 months. CONCLUSIONS:: This is the first randomised study to prospectively demonstrate reductions in SAT mtDNA in patients initiating AZT/3TC-containing ART but not in those initiating NRTI-sparing ART containing NVP and PI. That reductions in SAT mtDNA were also accompanied by lower limb fat suggests that use of ART not containing AZT/3TC may help prevent development of peripheral lipoatrophy.
Authors:
Eoin R Feeney; Marit G A van Vonderen; Ferdinand Wit; Sven A Danner; Michiel A van Agtmael; Francesc Villaroya; Pere Domingo; Jacqueline Capeau; Peter Reiss; Patrick W G Mallon;
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Publication Detail:
Type:  JOURNAL ARTICLE     Date:  2012-8-7
Journal Detail:
Title:  AIDS (London, England)     Volume:  -     ISSN:  1473-5571     ISO Abbreviation:  AIDS     Publication Date:  2012 Aug 
Date Detail:
Created Date:  2012-8-9     Completed Date:  -     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  8710219     Medline TA:  AIDS     Country:  -    
Other Details:
Languages:  ENG     Pagination:  -     Citation Subset:  -    
Affiliation:
aHIV Molecular Research Group, School of Medicine and Medical Science, University College Dublin, Ireland bMedical Center Leeuwarden, Department of Internal Medicine, Leeuwarden, the Netherlands cAcademic Medical Center, Department of Global Health, Amsterdam, the Netherlands dDepartment of Internal Medicine, VU Medical Center, Amsterdam, the Netherlands eUniversitat de Barcelona, Barcelona, Spain fCIBER Fisiopatologia de la Obesidad y Nutrición, Barcelona, Spain gHospital de la Santa Creu/Sant Pau, Barcelona, Spain hUniversite Paris 6, INSERM UMRS 938, Paris, France iAcademic Medical Center, Division of Infectious Diseases, Amsterdam, the Netherlands.
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