{"id":8586,"date":"2005-04-18T09:31:51","date_gmt":"2005-04-18T09:31:51","guid":{"rendered":"http:\/\/i-base.info\/htb\/?p=8586"},"modified":"2014-05-21T18:36:31","modified_gmt":"2014-05-21T18:36:31","slug":"continued-use-of-a-thymidine-analogue-may-limit-benefit-from-rosiglitazone-when-used-to-treat-lipoatrophy","status":"publish","type":"post","link":"https:\/\/i-base.info\/htb\/8586","title":{"rendered":"Continued use of a thymidine analogue may limit benefit from rosiglitazone when used to treat lipoatrophy"},"content":{"rendered":"

Simon Collins, HIV i-Base<\/strong><\/p>\n

Previous articles in HTB have tracked the rationale for potential benefit of rosiglitazone (RSG), a PPARg agonist and transcription regulator, to reverse lipoatrophy, together with reports from several studies that found conflicting clinical results, but generally found no benefit.<\/strong><\/p>\n

HIV-positive patients with lipoatrophy have decreased PPAR-g and rosiglitazone has increased limb fat in HIV-negative adults with Type-2 Diabetes Mellitis (who also have reduces PPAR-g). A report from last years Lipodystrophy Workshop highlighted a study from Patrick Mallon showing that thymidine analogues could work downstream of any beneficial effect, negating any potential benefit. [1]<\/p>\n

Dr Mallon brought new data to the Retrovirus meeting that analysed responses to rosiglitazone by continued use of background thymidine analogue that appears to confirm this finding clinicallly.<\/p>\n

Mallon reported on 44 men (4mg RSG BID n = 21; placebo n = 23) to a sub-study of the 48 week ROSEY rosiglitazone study. 21 were receiving the thymidine analogues (tNRTI) zidovudine (AZT) (n = 3) or stavudine (d4T) (n = 18) at baseline. Changes in mitochondrial RNA (mRNA) in fat biopsies and lipid metabolism genes were analysed at 0, 2 and 48 weeks.<\/p>\n

At week 2, only those randomized to RSG in the no-tNRTI group experienced a significant rise in PPAR-g expression (p<\/em> = 0.046). Similar significant increases in PPAR-g co-activator 1 (PGC-1) expression were also observed in the RSG no-tNRTI group. At week 48, PPAR-g expression was significantly higher only in the no-tNRTI group, regardless of randomised treatment allocation (p<\/em> = 0.04), with RSG having no effect in the tNRTI group.<\/p>\n

However, no significant correlations were observed between changes in PPAR-g or PGC-1 expression and change in limb fat.<\/p>\n

Comment<\/h3>\n

Although it is disappointing that no clinical benefit could be seen even when increased levels of PPAR-g were achieved without the use of thymidine analogues, this may be a reason to look again at this class of drugs, perhaps using pioglitazone, which does not increase cholesterol or triglycerides.<\/strong><\/p>\n

References:<\/p>\n

    \n
  1. Nucleosides reduce PPAR-gamma: a role for rosiglitazone without thymidine analogues<\/a>.
    \nReport form 6th Lipodystrophy Workshop. HIV Treatment Bulletin, December2004\/January 2005.<\/li>\n
  2. Mallon P, Sedwell R, Rogers G et al. The effect of rosiglitazone on PPARg expression in human adipose tissue Is limited by continued exposure to thymidine NRTI. 12th CROI, Boston, 2005.
    \n    Abstract 41<\/a>.<\/li>\n<\/ol>\n","protected":false},"excerpt":{"rendered":"

    Simon Collins, HIV i-Base Previous articles in HTB have tracked the rationale for potential benefit of rosiglitazone (RSG), a PPARg agonist and transcription regulator, to reverse lipoatrophy, together with reports from several studies that found conflicting clinical results, but generally …<\/p>\n","protected":false},"author":4,"featured_media":0,"comment_status":"open","ping_status":"closed","sticky":false,"template":"","format":"standard","meta":{"footnotes":""},"categories":[4,8,27],"tags":[59],"class_list":["post-8586","post","type-post","status-publish","format-standard","hentry","category-conference-reports","category-side-effects","category-weight-diabetes-metabolic-complications","tag-croi-2005"],"_links":{"self":[{"href":"https:\/\/i-base.info\/htb\/wp-json\/wp\/v2\/posts\/8586","targetHints":{"allow":["GET"]}}],"collection":[{"href":"https:\/\/i-base.info\/htb\/wp-json\/wp\/v2\/posts"}],"about":[{"href":"https:\/\/i-base.info\/htb\/wp-json\/wp\/v2\/types\/post"}],"author":[{"embeddable":true,"href":"https:\/\/i-base.info\/htb\/wp-json\/wp\/v2\/users\/4"}],"replies":[{"embeddable":true,"href":"https:\/\/i-base.info\/htb\/wp-json\/wp\/v2\/comments?post=8586"}],"version-history":[{"count":0,"href":"https:\/\/i-base.info\/htb\/wp-json\/wp\/v2\/posts\/8586\/revisions"}],"wp:attachment":[{"href":"https:\/\/i-base.info\/htb\/wp-json\/wp\/v2\/media?parent=8586"}],"wp:term":[{"taxonomy":"category","embeddable":true,"href":"https:\/\/i-base.info\/htb\/wp-json\/wp\/v2\/categories?post=8586"},{"taxonomy":"post_tag","embeddable":true,"href":"https:\/\/i-base.info\/htb\/wp-json\/wp\/v2\/tags?post=8586"}],"curies":[{"name":"wp","href":"https:\/\/api.w.org\/{rel}","templated":true}]}}