Incidence and determinants of nevirapine and efavirenz-related skin rashes in West Africans: nevirapine's epitaph?
Identifieur interne : 000584 ( PubMed/Corpus ); précédent : 000583; suivant : 000585Incidence and determinants of nevirapine and efavirenz-related skin rashes in West Africans: nevirapine's epitaph?
Auteurs : Fred Stephen Sarfo ; Maame Anima Sarfo ; Betty Norman ; Richard Phillips ; David ChadwickSource :
- PloS one [ 1932-6203 ] ; 2014.
English descriptors
- KwdEn :
- Adult, Anti-HIV Agents (adverse effects), Benzoxazines (adverse effects), Exanthema (chemically induced), Exanthema (diagnosis), Exanthema (epidemiology), Female, Ghana (epidemiology), Humans, Incidence, Male, Middle Aged, Nevirapine (adverse effects), Retrospective Studies, Risk Factors, Severity of Illness Index.
- MESH :
- chemical , adverse effects : Anti-HIV Agents, Benzoxazines, Nevirapine.
- geographic , epidemiology : Ghana.
- chemically induced : Exanthema.
- diagnosis : Exanthema.
- epidemiology : Exanthema.
- Adult, Female, Humans, Incidence, Male, Middle Aged, Retrospective Studies, Risk Factors, Severity of Illness Index.
Abstract
Non-nucleoside reverse transcriptase inhibitor (NNRTI) associated rash is common and frequently leads to discontinuation of NNRTIs. This study assessed the risk of developing rashes and discontinuing NNRTIs and associated factors in a large clinic in central Ghana. In this retrospective cohort study, clinical data were obtained in patients starting efavirenz or nevirapine between 2004-2010. Factors associated with rashes were explored using a multivariate Cox proportional hazards regression model. Of 3,999 patients who started NNRTI-based ART, 281 (7.0%) experienced at least one episode of NNRTI-related rash with an incidence of 2.63 events/100 person-years, occurring in 10.2% and 5.6% of patients taking nevirapine and efavirenz respectively. Most rashes (94%) were grade 1 or 2 and were reported a median of 2 months following initiation of ART. In multivariate analysis developing a rash was associated with nevirapine use (aHR 1.67, 95% CI 1.28-2.10), female gender (aHR of 1.39, 95% CI 1.01-1.92) and lower baseline CD4 counts (aHR 0.88, 95% CI 0.82-0.95 per 50 cells/mm³ increment). Patients with nevirapine-associated rash were 11 times more likely to discontinue treatment as patients with efavirenz-associated rash. In contrast to findings in other studies, NNRTI-associated rashes in Ghanaians appear more common in patients with lower baseline CD4 counts. Given the increased frequency of rashes with nevirapine and subsequent discontinuations in many patients, along with other treatment-limiting toxicities, this provides further impetus for the replacement of nevirapine by efavirenz as the first-line NNRTI treatment of choice in Africa.
DOI: 10.1371/journal.pone.0094854
PubMed: 24728406
Links to Exploration step
pubmed:24728406Le document en format XML
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Department of Medicine, Kwame Nkrumah University of Science and Technology, Kumasi, Ghana.</nlm:affiliation></affiliation></author><author><name sortKey="Chadwick, David" sort="Chadwick, David" uniqKey="Chadwick D" first="David" last="Chadwick">David Chadwick</name><affiliation><nlm:affiliation>Centre for Clinical Infection, The James Cook University Hospital, Middlesbrough, United Kingdom.</nlm:affiliation></affiliation></author></titleStmt><publicationStmt><idno type="wicri:source">PubMed</idno><date when="2014">2014</date><idno type="RBID">pubmed:24728406</idno><idno type="pmid">24728406</idno><idno type="doi">10.1371/journal.pone.0094854</idno><idno type="wicri:Area/PubMed/Corpus">000584</idno><idno type="wicri:explorRef" wicri:stream="PubMed" wicri:step="Corpus" wicri:corpus="PubMed">000584</idno></publicationStmt><sourceDesc><biblStruct><analytic><title xml:lang="en">Incidence and determinants of nevirapine and efavirenz-related skin rashes in West Africans: nevirapine's epitaph?</title><author><name sortKey="Sarfo, Fred Stephen" sort="Sarfo, Fred Stephen" uniqKey="Sarfo F" first="Fred Stephen" last="Sarfo">Fred Stephen Sarfo</name><affiliation><nlm:affiliation>Department of Medicine, Komfo Anokye Teaching Hospital, Kumasi, Ghana; Department of Medicine, Kwame Nkrumah University of Science and Technology, Kumasi, Ghana.</nlm:affiliation></affiliation></author><author><name sortKey="Sarfo, Maame Anima" sort="Sarfo, Maame Anima" uniqKey="Sarfo M" first="Maame Anima" last="Sarfo">Maame Anima Sarfo</name><affiliation><nlm:affiliation>Department of Medicine, Komfo Anokye Teaching Hospital, Kumasi, Ghana.</nlm:affiliation></affiliation></author><author><name sortKey="Norman, Betty" sort="Norman, Betty" uniqKey="Norman B" first="Betty" last="Norman">Betty Norman</name><affiliation><nlm:affiliation>Department of Medicine, Komfo Anokye Teaching Hospital, Kumasi, Ghana.</nlm:affiliation></affiliation></author><author><name sortKey="Phillips, Richard" sort="Phillips, Richard" uniqKey="Phillips R" first="Richard" last="Phillips">Richard Phillips</name><affiliation><nlm:affiliation>Department of Medicine, Komfo Anokye Teaching Hospital, Kumasi, Ghana; Department of Medicine, Kwame Nkrumah University of Science and Technology, Kumasi, Ghana.</nlm:affiliation></affiliation></author><author><name sortKey="Chadwick, David" sort="Chadwick, David" uniqKey="Chadwick D" first="David" last="Chadwick">David Chadwick</name><affiliation><nlm:affiliation>Centre for Clinical Infection, The James Cook University Hospital, Middlesbrough, United Kingdom.</nlm:affiliation></affiliation></author></analytic><series><title level="j">PloS one</title><idno type="eISSN">1932-6203</idno><imprint><date when="2014" type="published">2014</date></imprint></series></biblStruct></sourceDesc></fileDesc><profileDesc><textClass><keywords scheme="KwdEn" xml:lang="en"><term>Adult</term><term>Anti-HIV Agents (adverse effects)</term><term>Benzoxazines (adverse effects)</term><term>Exanthema (chemically induced)</term><term>Exanthema (diagnosis)</term><term>Exanthema (epidemiology)</term><term>Female</term><term>Ghana (epidemiology)</term><term>Humans</term><term>Incidence</term><term>Male</term><term>Middle Aged</term><term>Nevirapine (adverse effects)</term><term>Retrospective Studies</term><term>Risk Factors</term><term>Severity of Illness Index</term></keywords><keywords scheme="MESH" type="chemical" qualifier="adverse effects" xml:lang="en"><term>Anti-HIV Agents</term><term>Benzoxazines</term><term>Nevirapine</term></keywords><keywords scheme="MESH" type="geographic" qualifier="epidemiology" xml:lang="en"><term>Ghana</term></keywords><keywords scheme="MESH" qualifier="chemically induced" xml:lang="en"><term>Exanthema</term></keywords><keywords scheme="MESH" qualifier="diagnosis" xml:lang="en"><term>Exanthema</term></keywords><keywords scheme="MESH" qualifier="epidemiology" xml:lang="en"><term>Exanthema</term></keywords><keywords scheme="MESH" xml:lang="en"><term>Adult</term><term>Female</term><term>Humans</term><term>Incidence</term><term>Male</term><term>Middle Aged</term><term>Retrospective Studies</term><term>Risk Factors</term><term>Severity of Illness Index</term></keywords></textClass></profileDesc></teiHeader><front><div type="abstract" xml:lang="en">Non-nucleoside reverse transcriptase inhibitor (NNRTI) associated rash is common and frequently leads to discontinuation of NNRTIs. This study assessed the risk of developing rashes and discontinuing NNRTIs and associated factors in a large clinic in central Ghana. In this retrospective cohort study, clinical data were obtained in patients starting efavirenz or nevirapine between 2004-2010. Factors associated with rashes were explored using a multivariate Cox proportional hazards regression model. Of 3,999 patients who started NNRTI-based ART, 281 (7.0%) experienced at least one episode of NNRTI-related rash with an incidence of 2.63 events/100 person-years, occurring in 10.2% and 5.6% of patients taking nevirapine and efavirenz respectively. Most rashes (94%) were grade 1 or 2 and were reported a median of 2 months following initiation of ART. In multivariate analysis developing a rash was associated with nevirapine use (aHR 1.67, 95% CI 1.28-2.10), female gender (aHR of 1.39, 95% CI 1.01-1.92) and lower baseline CD4 counts (aHR 0.88, 95% CI 0.82-0.95 per 50 cells/mm³ increment). Patients with nevirapine-associated rash were 11 times more likely to discontinue treatment as patients with efavirenz-associated rash. In contrast to findings in other studies, NNRTI-associated rashes in Ghanaians appear more common in patients with lower baseline CD4 counts. Given the increased frequency of rashes with nevirapine and subsequent discontinuations in many patients, along with other treatment-limiting toxicities, this provides further impetus for the replacement of nevirapine by efavirenz as the first-line NNRTI treatment of choice in Africa.</div></front></TEI><pubmed><MedlineCitation Status="MEDLINE" Owner="NLM"><PMID Version="1">24728406</PMID><DateCreated><Year>2014</Year><Month>04</Month><Day>14</Day></DateCreated><DateCompleted><Year>2015</Year><Month>05</Month><Day>29</Day></DateCompleted><DateRevised><Year>2017</Year><Month>09</Month><Day>02</Day></DateRevised><Article PubModel="Electronic-eCollection"><Journal><ISSN IssnType="Electronic">1932-6203</ISSN><JournalIssue CitedMedium="Internet"><Volume>9</Volume><Issue>4</Issue><PubDate><Year>2014</Year></PubDate></JournalIssue><Title>PloS one</Title><ISOAbbreviation>PLoS ONE</ISOAbbreviation></Journal><ArticleTitle>Incidence and determinants of nevirapine and efavirenz-related skin rashes in West Africans: nevirapine's epitaph?</ArticleTitle><Pagination><MedlinePgn>e94854</MedlinePgn></Pagination><ELocationID EIdType="doi" ValidYN="Y">10.1371/journal.pone.0094854</ELocationID><Abstract><AbstractText>Non-nucleoside reverse transcriptase inhibitor (NNRTI) associated rash is common and frequently leads to discontinuation of NNRTIs. This study assessed the risk of developing rashes and discontinuing NNRTIs and associated factors in a large clinic in central Ghana. In this retrospective cohort study, clinical data were obtained in patients starting efavirenz or nevirapine between 2004-2010. Factors associated with rashes were explored using a multivariate Cox proportional hazards regression model. Of 3,999 patients who started NNRTI-based ART, 281 (7.0%) experienced at least one episode of NNRTI-related rash with an incidence of 2.63 events/100 person-years, occurring in 10.2% and 5.6% of patients taking nevirapine and efavirenz respectively. Most rashes (94%) were grade 1 or 2 and were reported a median of 2 months following initiation of ART. In multivariate analysis developing a rash was associated with nevirapine use (aHR 1.67, 95% CI 1.28-2.10), female gender (aHR of 1.39, 95% CI 1.01-1.92) and lower baseline CD4 counts (aHR 0.88, 95% CI 0.82-0.95 per 50 cells/mm³ increment). Patients with nevirapine-associated rash were 11 times more likely to discontinue treatment as patients with efavirenz-associated rash. In contrast to findings in other studies, NNRTI-associated rashes in Ghanaians appear more common in patients with lower baseline CD4 counts. Given the increased frequency of rashes with nevirapine and subsequent discontinuations in many patients, along with other treatment-limiting toxicities, this provides further impetus for the replacement of nevirapine by efavirenz as the first-line NNRTI treatment of choice in Africa.</AbstractText></Abstract><AuthorList CompleteYN="Y"><Author ValidYN="Y"><LastName>Sarfo</LastName><ForeName>Fred Stephen</ForeName><Initials>FS</Initials><AffiliationInfo><Affiliation>Department of Medicine, Komfo Anokye Teaching Hospital, Kumasi, Ghana; Department of Medicine, Kwame Nkrumah University of Science and Technology, Kumasi, Ghana.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Sarfo</LastName><ForeName>Maame Anima</ForeName><Initials>MA</Initials><AffiliationInfo><Affiliation>Department of Medicine, Komfo Anokye Teaching Hospital, Kumasi, Ghana.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Norman</LastName><ForeName>Betty</ForeName><Initials>B</Initials><AffiliationInfo><Affiliation>Department of Medicine, Komfo Anokye Teaching Hospital, Kumasi, Ghana.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Phillips</LastName><ForeName>Richard</ForeName><Initials>R</Initials><AffiliationInfo><Affiliation>Department of Medicine, Komfo Anokye Teaching Hospital, Kumasi, Ghana; Department of Medicine, Kwame Nkrumah University of Science and Technology, Kumasi, Ghana.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Chadwick</LastName><ForeName>David</ForeName><Initials>D</Initials><AffiliationInfo><Affiliation>Centre for Clinical Infection, The James Cook University Hospital, Middlesbrough, United Kingdom.</Affiliation></AffiliationInfo></Author></AuthorList><Language>eng</Language><GrantList CompleteYN="Y"><Grant><GrantID>MRC_MR/J01477X/1</GrantID><Agency>Medical Research Council</Agency><Country>United Kingdom</Country></Grant></GrantList><PublicationTypeList><PublicationType UI="D016428">Journal Article</PublicationType><PublicationType UI="D013485">Research Support, Non-U.S. Gov't</PublicationType></PublicationTypeList><ArticleDate DateType="Electronic"><Year>2014</Year><Month>04</Month><Day>11</Day></ArticleDate></Article><MedlineJournalInfo><Country>United States</Country><MedlineTA>PLoS One</MedlineTA><NlmUniqueID>101285081</NlmUniqueID><ISSNLinking>1932-6203</ISSNLinking></MedlineJournalInfo><ChemicalList><Chemical><RegistryNumber>0</RegistryNumber><NameOfSubstance UI="D019380">Anti-HIV Agents</NameOfSubstance></Chemical><Chemical><RegistryNumber>0</RegistryNumber><NameOfSubstance UI="D048588">Benzoxazines</NameOfSubstance></Chemical><Chemical><RegistryNumber>99DK7FVK1H</RegistryNumber><NameOfSubstance UI="D019829">Nevirapine</NameOfSubstance></Chemical><Chemical><RegistryNumber>JE6H2O27P8</RegistryNumber><NameOfSubstance UI="C098320">efavirenz</NameOfSubstance></Chemical></ChemicalList><CitationSubset>IM</CitationSubset><CommentsCorrectionsList><CommentsCorrections RefType="Cites"><RefSource>J Antimicrob Chemother. 2014 Jan;69(1):254-61</RefSource><PMID Version="1">24003181</PMID></CommentsCorrections><CommentsCorrections RefType="Cites"><RefSource>AIDS. 2013 Mar 13;27(5):803-13</RefSource><PMID Version="1">23719350</PMID></CommentsCorrections><CommentsCorrections RefType="Cites"><RefSource>Antivir Ther. 2007;12(5):753-60</RefSource><PMID Version="1">17713158</PMID></CommentsCorrections><CommentsCorrections RefType="Cites"><RefSource>Trans R Soc Trop Med Hyg. 2010 Feb;104(2):148-53</RefSource><PMID Version="1">19732926</PMID></CommentsCorrections><CommentsCorrections RefType="Cites"><RefSource>AIDS. 2005 Jan 28;19(2):185-92</RefSource><PMID Version="1">15668544</PMID></CommentsCorrections><CommentsCorrections RefType="Cites"><RefSource>Lancet Infect Dis. 2007 Nov;7(11):733-8</RefSource><PMID 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effects</QualifierName></MeshHeading><MeshHeading><DescriptorName UI="D005076" MajorTopicYN="N">Exanthema</DescriptorName><QualifierName UI="Q000139" MajorTopicYN="Y">chemically induced</QualifierName><QualifierName UI="Q000175" MajorTopicYN="N">diagnosis</QualifierName><QualifierName UI="Q000453" MajorTopicYN="Y">epidemiology</QualifierName></MeshHeading><MeshHeading><DescriptorName UI="D005260" MajorTopicYN="N">Female</DescriptorName></MeshHeading><MeshHeading><DescriptorName UI="D005869" MajorTopicYN="N" Type="Geographic">Ghana</DescriptorName><QualifierName UI="Q000453" MajorTopicYN="N">epidemiology</QualifierName></MeshHeading><MeshHeading><DescriptorName UI="D006801" MajorTopicYN="N">Humans</DescriptorName></MeshHeading><MeshHeading><DescriptorName UI="D015994" MajorTopicYN="N">Incidence</DescriptorName></MeshHeading><MeshHeading><DescriptorName UI="D008297" MajorTopicYN="N">Male</DescriptorName></MeshHeading><MeshHeading><DescriptorName UI="D008875" MajorTopicYN="N">Middle Aged</DescriptorName></MeshHeading><MeshHeading><DescriptorName UI="D019829" MajorTopicYN="N">Nevirapine</DescriptorName><QualifierName UI="Q000009" MajorTopicYN="Y">adverse effects</QualifierName></MeshHeading><MeshHeading><DescriptorName UI="D012189" MajorTopicYN="N">Retrospective Studies</DescriptorName></MeshHeading><MeshHeading><DescriptorName UI="D012307" MajorTopicYN="N">Risk Factors</DescriptorName></MeshHeading><MeshHeading><DescriptorName UI="D012720" MajorTopicYN="N">Severity of Illness Index</DescriptorName></MeshHeading></MeshHeadingList><OtherID Source="NLM">PMC3984248</OtherID></MedlineCitation><PubmedData><History><PubMedPubDate PubStatus="received"><Year>2013</Year><Month>12</Month><Day>09</Day></PubMedPubDate><PubMedPubDate PubStatus="accepted"><Year>2014</Year><Month>03</Month><Day>20</Day></PubMedPubDate><PubMedPubDate PubStatus="entrez"><Year>2014</Year><Month>4</Month><Day>15</Day><Hour>6</Hour><Minute>0</Minute></PubMedPubDate><PubMedPubDate 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