{"id":1658,"date":"2009-06-03T18:46:47","date_gmt":"2009-06-03T18:46:47","guid":{"rendered":"http:\/\/localhost.localdomain\/wpmu\/htb\/?p=1658"},"modified":"2013-08-16T13:42:12","modified_gmt":"2013-08-16T13:42:12","slug":"cd4-count-250-not-predictive-of-rash-associated-hepatoxicity-among-women-initiating-nevirapine-based-art-in-zambia-thailand-and-kenya","status":"publish","type":"post","link":"https:\/\/i-base.info\/htb\/1658","title":{"rendered":"CD4 count >250 not predictive of rash-associated hepatoxicity among women initiating nevirapine-based ART in Zambia, Thailand, and Kenya"},"content":{"rendered":"<p><strong>Polly Clayden, HIV i-Base<\/strong><\/p>\n<p><strong>Nevirapine (NVP)-containing HAART is the most frequently used regimen in resource-limited countries.<\/strong><\/p>\n<p>In 2004 Boehringer-Ingelheim, manufacturers of nevirapine (Viramune) performed a retrospective analysis of hepatoxicity events among 633 women receiving NVP within the company\u0092s trials. This analysis revealed 11% women having hepatoxicity with pre-treatment CD4 count &gt;250 cells\/mm3 vs 0.9% with CD4 &lt;250 cells\/mm3. Following these results the company changed the Summary of Product Characteristics to include a caution that women with higher CD4 counts are at increased risk of hepatic toxicity.<\/p>\n<p>The trials included in this analysis were conducted in Western Europe and North America. There are few data available from women initiating NVP-containing HAART in Africa and Asia. A poster from Anouk Kesselring which looked at this issue using data from several cohorts.<\/p>\n<p>A poster from Philip Peters and coworkers from the CDC and centres in Zambia, Thailand and Kenya, showed findings from an evaluation of risk factors for rash-associated toxicity among women receiving NVP-containing ART between May 2005 and January 2007 in this multi-country cohort. This was a prospective observational study.<\/p>\n<p>The investigators included 820 (497 Zambian, 192 Thai, and 131 Kenyan) treatment-naive women initiating NVP-containing ART in this analysis. Women received ART in accordance with national guidelines. NVP was initiated at half dose for the first two weeks of treatment.<\/p>\n<p>Liver function tests (LFTs) were performed at 2, 4, 8, 16, and 24 weeks. Women also received a clinical evaluation for rash. Hepatoxicity was graded:<\/p>\n<ul>\n<li>Grade 1 &#8211; mild (transaminase [AST or ALT] elevation 1.25 to 2.49 times the upper limit of normal [x ULN]), 50-99;<\/li>\n<li>Grade 2 &#8211; moderate (2.5 to 4.99 x ULN), 100-199; and<\/li>\n<li>Grade 3 &#8211; severe (&gt;5.0 x ULN), &gt;200.<\/li>\n<\/ul>\n<p>Rash associated hepatoxicity (RAH) was defined as an ALT or AST elevation &gt; grade 2 with concomitant rash. The investigators used multivariate analysis to identify variables associated with hepatoxicity and RAH.<\/p>\n<p>At baseline women were a median age of 32 years (IQR 28-36) with a median CD4 count 149 cells\/mm3 (IQR 83-215) and 86% had normal LFTs. The investigators reported that hepatotoxicity (&gt; grade 2) occurred in 109 (13%) women and for 41 (5%) it was severe. In multivariate analysis abnormal baseline LFT was associated with severe hepatoxicity AOR 3.0 (95%CI 1.4-6.2).<\/p>\n<p>RAH occurred in 27 (3%) women (Zambia 2%, Thailand 7%, Kenya 2%). Of these 8\/123 (6.5%) women had a baseline CD4 &lt;50 cells\/mm3; 13\/576 (2%) had a CD4 of 50 to 250 cells\/mm3; and 6\/121 (5%) women with a CD4 &gt;250 cells\/mm3.<\/p>\n<p>RAH was also significantly associated with abnormal LFT at baseline, AOR 3.1 (95% CI 1.2- 8.2). Thai ethnicity AOR 4.5 (95%CI 1.8-11.4) was also associated with RAH.<\/p>\n<p>Baseline CD4 &gt;250 cells\/mm3 was not associated with either severe hepatoxicity [AOR 1.1; 95%CI 0.4-2.7] or RAH [AOR 1.6; 95%CI 0.6-4.4]. When the investigators looked at the frequency of RAH and severe hepatoxicity stratified by CD4 count, women &lt;50 cells\/mm3 had the highest rates; 7% and 6.5% of RAH and severe hepatoxicity respectively. They also noted that there was an increased risk for RAH at CD4 &gt;200 cells\/mm3 vs 50-199 cells\/mm3, p=0.004.<\/p>\n<p>Three women (0.4%) died with symptoms suggestive of fatal hepatotoxicity, All 3 deaths had a baseline CD4 &lt;100 cells\/mm3 in women being treated for tuberculosis.<\/p>\n<p>The investigators wrote: \u0093Public health officials should be aware that limiting nevirapine use to women with a CD4 cell count &lt;250 cells\/mm3 may not limit hepatotoxicity.\u0094<\/p>\n<h3>Comment<\/h3>\n<p><strong>While restricting nevirapine use to men with CD4 count &lt;400\u00a0 cells\/mm3 and women with CD4 count &lt;250 cells\/ mm3 will improve the safe use of this highly effective therapy, the introduction of nevirapine should always be with caution and careful monitoring.<\/strong><\/p>\n<p><strong>As noted in this study, patients eligible for treatment with nevirapine, especially women, will have low CD4 counts and are therefore often at risk of opportunistic infections.<\/strong><\/p>\n<p><strong>The case for using nevirapine in conjunction with other hepatotoxic therapies (eg common antituberculosis therapies) or in patients with abnormal LFTs, should always be carefully considered.<\/strong><\/p>\n<p><strong>Gender and ethnic differences in drug handling are emerging as important factors andconclusions from studies based on selected populations cannot necessarily be generalised.<\/strong><\/p>\n<p>Reference:<\/p>\n<p>Peters et al. CD4 cell count &gt;250 Cells\/mm3 does not predict rash-associated hepatotoxicity among women initiating nevirapine-based ART in Zambia, Thailand, and Kenya. 16th CROI, February 2009, Montreal, Canada. Poster abstract 986.<a href=\"http:\/\/www.retroconference.org\/2009\/Abstracts\/33861.htm\"><br \/>\nhttp:\/\/www.retroconference.org\/2009\/Abstracts\/33861.htm<\/a><\/p>\n","protected":false},"excerpt":{"rendered":"<p>Polly Clayden, HIV i-Base Nevirapine (NVP)-containing HAART is the most frequently used regimen in resource-limited countries. In 2004 Boehringer-Ingelheim, manufacturers of nevirapine (Viramune) performed a retrospective analysis of hepatoxicity events among 633 women receiving NVP within the company\u0092s trials. This &hellip;<\/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],"tags":[63],"class_list":["post-1658","post","type-post","status-publish","format-standard","hentry","category-conference-reports","category-side-effects","tag-croi-2009"],"_links":{"self":[{"href":"https:\/\/i-base.info\/htb\/wp-json\/wp\/v2\/posts\/1658","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=1658"}],"version-history":[{"count":0,"href":"https:\/\/i-base.info\/htb\/wp-json\/wp\/v2\/posts\/1658\/revisions"}],"wp:attachment":[{"href":"https:\/\/i-base.info\/htb\/wp-json\/wp\/v2\/media?parent=1658"}],"wp:term":[{"taxonomy":"category","embeddable":true,"href":"https:\/\/i-base.info\/htb\/wp-json\/wp\/v2\/categories?post=1658"},{"taxonomy":"post_tag","embeddable":true,"href":"https:\/\/i-base.info\/htb\/wp-json\/wp\/v2\/tags?post=1658"}],"curies":[{"name":"wp","href":"https:\/\/api.w.org\/{rel}","templated":true}]}}