{"id":7801,"date":"2010-02-14T00:04:39","date_gmt":"2010-02-14T00:04:39","guid":{"rendered":"http:\/\/moomango.co.uk\/htb\/?p=7801"},"modified":"2013-08-06T07:15:32","modified_gmt":"2013-08-06T07:15:32","slug":"pregnancy-not-nevirapine-associated-with-risk-of-hepatotoxicity-in-large-cohort-comparison","status":"publish","type":"post","link":"https:\/\/i-base.info\/htb\/7801","title":{"rendered":"Pregnancy not nevirapine associated with risk of hepatotoxicity in large cohort comparison"},"content":{"rendered":"

Polly Clayden, HIV\u00a0i-Base<\/strong><\/p>\n

There is some uncertainty about the association between nevirapine, pregnancy and hepatotoxicity in HIV-positive women. <\/strong><\/p>\n

In a concise communication,\u00a0published in the November 27 2009 edition of AIDS, David Ouyang and investigators from two large American multicentre cohorts, the Women and Infants\u00a0Transmission Study (WITS) and the International Maternal Paediatric Adolescent Clinical Trials (IMPAACT) protocol P1025, showed findings from a study to\u00a0estimate whether this association differs by pregnancy status in HIV-positive women.<\/p>\n

The study compared pregnant women in WITS and IMPAACT to a non-pregnant reference group from the Women Interagency HIV Study (WIHS).<\/p>\n

Cox proportional hazard models were used to investigate the association between nevirapine use and any liver enzyme elevation (LEE, grade 1-4) and severe\u00a0LEE (grade 3-4). Potential confounders included pregnancy status.<\/p>\n

The analysis included a total of 2050 HIV-positive women receiving HAART of which 60% were pregnant.<\/p>\n

Pregnant women in this analysis were younger than non-pregnant, mean age 27.99 vs 35.96, p<0.001. They had higher CD4, lower viral loads and had been\u00a0HIV-positive for a shorter duration of time. They also had less chronic hepatitis and were more likely to be both ART and nevirapine naive. A similar\u00a0proportion of pregnant and non-pregnant women had been exposed to nevirapine, with a greater proportion of non-pregnant women having CD4 >=250\u00a0cells\/mm3<\/sup>. See Table 1.<\/p>\n

Table 1. CD4 cell count of women receiving NVP by pregnancy status<\/strong><\/p>\n\n\n\n\n\n\n
<\/td>\nn<\/strong><\/td>\n%<\/strong><\/td>\nn<\/strong><\/td>\n%<\/strong><\/td>\np<\/strong><\/td>\n<\/tr>\n
NVP<\/strong><\/td>\n218<\/td>\n17.73<\/td>\n169<\/td>\n20.58<\/td>\n0.106<\/td>\n<\/tr>\n
CD4<=250c\/\u00b5L<\/strong><\/td>\n50<\/td>\n23.81<\/td>\n22<\/td>\n13.92<\/td>\n<\/td>\n<\/tr>\n
CD4>=250c\/\u00b5L<\/strong><\/td>\n160<\/td>\n76.19<\/td>\n136<\/td>\n86.08<\/td>\n0.018<\/td>\n<\/tr>\n<\/tbody>\n<\/table>\n

Overall the\u00a0investigators found pregnant women were significantly more likely than non-pregnant women to develop any LEE, 14.2 vs 9.1% respectively, p=0.0001. They\u00a0also had a higher rate of severe LEE, 1.2 vs 0.6%, although this difference did not reach statistical significance.<\/p>\n

Multivariate analysis found pregnancy to be significantly associated with any LEE, RR 4.7 (95% CI, 3.39-6.53, p<0.01 and with severe LEE, RR 3.8 (95%\u00a0CI, 1.3-11.1). However, nevirapine was not significantly associated with any LEE, RR 1.17 (95% CI, 0.8-1.7) or severe LEE, RR 1.78 (95% CI 0.4-7.82) and\u00a0this was regardless of pregnancy status. The investigators noted that due to concerns in the literature about nevirapine exposure at higher CD4 counts,\u00a0these variables were included in the multivariate models despite not being significant in univariate analysis and they continued to demonstrate no\u00a0association with LEE.<\/p>\n

Thee investigators wrote: \u0093While we support close monitoring for clinical or laboratory evidence of hepatotoxicity with any ART regimen, our results\u00a0challenge the notion that NVP is uniquely associated with hepatotoxicity during pregnancy.\u0094<\/p>\n

COMMENT<\/strong><\/p>\n

It seems likely that pregnancy does not increase the risk of nevirapine-related toxicity at CD4 counts below 250 cells\/mm3<\/sup> and is therefore safe\u00a0to prescribe in pregnancy in accordance with current guidelines.<\/strong><\/p>\n

However, it gets more complicated with regard to safety of nevirapine in pregnant women with CD4 counts greater than 250 cells\/mm3<\/sup>, and this\u00a0study, along with others, is not showing any signal or nevirapine-associated toxicity in pregnancy.<\/strong><\/p>\n

It is also notable that expert panel reviews for new WHO guidance did not confirm an increase of serious adverse events and concluded that the\u00a0benefits of using nevirapine in this situation outweigh the risks of not initiating ART (see our review of WHO guideline revisions).<\/strong><\/p>\n

Given the temporary pregnancy related immunodeficiency in addition to any HIV-related immunodeficiency it certainly seems sensible to re-run these\u00a0analyses at higher CD4 counts – eg 400 cells\/mm3<\/sup>.<\/strong><\/p>\n

Reference<\/p>\n

Ouyang et al. Increased risk of hepatotoxicity in HIV-infected pregnant women receiving antiretroviral therapy independent of nevirapine exposure. AIDS\u00a02009, 23:2425-2430.<\/p>\n","protected":false},"excerpt":{"rendered":"

Polly Clayden, HIV\u00a0i-Base There is some uncertainty about the association between nevirapine, pregnancy and hepatotoxicity in HIV-positive women. In a concise communication,\u00a0published in the November 27 2009 edition of AIDS, David Ouyang and investigators from two large American multicentre cohorts, …<\/p>\n","protected":false},"author":4,"featured_media":0,"comment_status":"open","ping_status":"closed","sticky":false,"template":"","format":"standard","meta":{"footnotes":""},"categories":[35],"tags":[],"class_list":["post-7801","post","type-post","status-publish","format-standard","hentry","category-pmtct-and-maternal-health"],"_links":{"self":[{"href":"https:\/\/i-base.info\/htb\/wp-json\/wp\/v2\/posts\/7801","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=7801"}],"version-history":[{"count":0,"href":"https:\/\/i-base.info\/htb\/wp-json\/wp\/v2\/posts\/7801\/revisions"}],"wp:attachment":[{"href":"https:\/\/i-base.info\/htb\/wp-json\/wp\/v2\/media?parent=7801"}],"wp:term":[{"taxonomy":"category","embeddable":true,"href":"https:\/\/i-base.info\/htb\/wp-json\/wp\/v2\/categories?post=7801"},{"taxonomy":"post_tag","embeddable":true,"href":"https:\/\/i-base.info\/htb\/wp-json\/wp\/v2\/tags?post=7801"}],"curies":[{"name":"wp","href":"https:\/\/api.w.org\/{rel}","templated":true}]}}