Adipose tissue morphology improved after treatment discontinuation
Simon Collins, HIV i-Base
Jacqueline Capeau, one of the lead researchers into metabolic changes associated with lipodystrophy, and one of the organisers of the workshop, presented results showing an improvement in sub-clinical markers for lipodystrophy in virologically controlled patients who discontinued treatment for 6 months.
Subcutaneous abdominal fat biopsies were taken at baseline from 40 patients and after six months for the 33 patients who completed the treatment interruption, and adipose tissue morphology examined in 29 patients.
Of these, treatments used in combinations were PI+NRTI (10), NRTI without PI (19), d4T (8), AZT (13), other RTI (12). Samples from 23 patients were tested for mitochondrial DNA and from 20 patients for adipose tissue gene expression (8 PI-based; 12 using NRTIs without PIs; 1 using d4T, 8 using AZT and 11 using other RTIs).
The six month treatment break did not change clinical symptoms or levels of fibrosis. However, adipose tissue inflammation was significantly improved with reduced lipogranuloma and macrophages (p=0.003 and 0.002 respectively). TNF-alpha and IL6 was only increased at baseline in patients using d4T or AZT, and adipocytes and inflammatory cells positive for both markers were markedly reduced after 6 months discontinuation of d4T or AZT (PI use did not affect this). Other improvements at month 6 in patients discontinuing d4T and AZT included increased mitochondrial DNA and reduced COX4 RNA and COX2/COX4 ratio.
PPAR-gamma and SREBP-1 are markers for adipocyte differentiation that previous studies have shown to be significantly reduced in patients with lipodystrophy, and patients stopping PIs showed improved levels of PPAR-gamma, PGC-1-alpha and COX2), and mitochondrial alterations, though at different levels.
The study took place prior to the results from the SMART treatment interruption study, and the researchers were not recommending treatment interruptions in patients now.
Instead the results are interpreted as showing the beneficial effects from removing a drug that negatively impacts on fat metabolism, and as additional data supporting active switching away from drugs associated with symptoms of lipodystrophy.
Capeau J et al. A six month interruption in HIV-infected patients improves adipose tissue morphology and gene expression (ANRS EP29 Lipostop). 8th IWADRLH, September 2006, San Francisco. Abstract 5.