Incidence and Determinants of Nevirapine and Efavirenz-Related Skin Rashes in West Africans: Nevirapine's Epitaph?
Identifieur interne : 000245 ( Pmc/Checkpoint ); précédent : 000244; suivant : 000246Incidence and Determinants of Nevirapine and Efavirenz-Related Skin Rashes in West Africans: Nevirapine's Epitaph?
Auteurs : Fred Stephen Sarfo [Ghana] ; Maame Anima Sarfo [Ghana] ; Betty Norman [Ghana] ; Richard Phillips [Ghana] ; David Chadwick [Royaume-Uni]Source :
- PLoS ONE [ 1932-6203 ] ; 2014.
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.
Url:
DOI: 10.1371/journal.pone.0094854
PubMed: 24728406
PubMed Central: 3984248
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<record><TEI><teiHeader><fileDesc><titleStmt><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 wicri:level="1"><nlm:aff id="aff1"><addr-line>Department of Medicine, Komfo Anokye Teaching Hospital, Kumasi, Ghana</addr-line></nlm:aff><country xml:lang="fr">Ghana</country><wicri:regionArea>Department of Medicine, Komfo Anokye Teaching Hospital, Kumasi</wicri:regionArea><wicri:noRegion>Kumasi</wicri:noRegion></affiliation><affiliation wicri:level="1"><nlm:aff id="aff2"><addr-line>Department of Medicine, Kwame Nkrumah University of Science and Technology, Kumasi, Ghana</addr-line></nlm:aff><country xml:lang="fr">Ghana</country><wicri:regionArea>Department of Medicine, Kwame Nkrumah University of Science and Technology, 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Kumasi</wicri:regionArea><wicri:noRegion>Kumasi</wicri:noRegion></affiliation></author><author><name sortKey="Phillips, Richard" sort="Phillips, Richard" uniqKey="Phillips R" first="Richard" last="Phillips">Richard Phillips</name><affiliation wicri:level="1"><nlm:aff id="aff1"><addr-line>Department of Medicine, Komfo Anokye Teaching Hospital, Kumasi, Ghana</addr-line></nlm:aff><country xml:lang="fr">Ghana</country><wicri:regionArea>Department of Medicine, Komfo Anokye Teaching Hospital, Kumasi</wicri:regionArea><wicri:noRegion>Kumasi</wicri:noRegion></affiliation><affiliation wicri:level="1"><nlm:aff id="aff2"><addr-line>Department of Medicine, Kwame Nkrumah University of Science and Technology, Kumasi, Ghana</addr-line></nlm:aff><country xml:lang="fr">Ghana</country><wicri:regionArea>Department of Medicine, Kwame Nkrumah University of Science and Technology, Kumasi</wicri:regionArea><wicri:noRegion>Kumasi</wicri:noRegion></affiliation></author><author><name sortKey="Chadwick, David" sort="Chadwick, David" uniqKey="Chadwick D" first="David" last="Chadwick">David Chadwick</name><affiliation wicri:level="1"><nlm:aff id="aff3"><addr-line>Centre for Clinical Infection, The James Cook University Hospital, Middlesbrough, United Kingdom</addr-line></nlm:aff><country xml:lang="fr">Royaume-Uni</country><wicri:regionArea>Centre for Clinical Infection, The James Cook University Hospital, Middlesbrough</wicri:regionArea><wicri:noRegion>Middlesbrough</wicri:noRegion></affiliation></author></titleStmt><publicationStmt><idno type="wicri:source">PMC</idno><idno type="pmid">24728406</idno><idno type="pmc">3984248</idno><idno type="url">http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3984248</idno><idno type="RBID">PMC:3984248</idno><idno type="doi">10.1371/journal.pone.0094854</idno><date when="2014">2014</date><idno type="wicri:Area/Pmc/Corpus">000488</idno><idno type="wicri:explorRef" wicri:stream="Pmc" wicri:step="Corpus" wicri:corpus="PMC">000488</idno><idno 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wicri:level="1"><nlm:aff id="aff2"><addr-line>Department of Medicine, Kwame Nkrumah University of Science and Technology, Kumasi, Ghana</addr-line></nlm:aff><country xml:lang="fr">Ghana</country><wicri:regionArea>Department of Medicine, Kwame Nkrumah University of Science and Technology, Kumasi</wicri:regionArea><wicri:noRegion>Kumasi</wicri:noRegion></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 wicri:level="1"><nlm:aff id="aff1"><addr-line>Department of Medicine, Komfo Anokye Teaching Hospital, Kumasi, Ghana</addr-line></nlm:aff><country xml:lang="fr">Ghana</country><wicri:regionArea>Department of Medicine, Komfo Anokye Teaching Hospital, Kumasi</wicri:regionArea><wicri:noRegion>Kumasi</wicri:noRegion></affiliation></author><author><name sortKey="Norman, Betty" sort="Norman, Betty" uniqKey="Norman B" first="Betty" last="Norman">Betty Norman</name><affiliation wicri:level="1"><nlm:aff id="aff1"><addr-line>Department of Medicine, Komfo Anokye Teaching Hospital, Kumasi, Ghana</addr-line></nlm:aff><country xml:lang="fr">Ghana</country><wicri:regionArea>Department of Medicine, Komfo Anokye Teaching Hospital, Kumasi</wicri:regionArea><wicri:noRegion>Kumasi</wicri:noRegion></affiliation></author><author><name sortKey="Phillips, Richard" sort="Phillips, Richard" uniqKey="Phillips R" first="Richard" last="Phillips">Richard Phillips</name><affiliation wicri:level="1"><nlm:aff id="aff1"><addr-line>Department of Medicine, Komfo Anokye Teaching Hospital, Kumasi, Ghana</addr-line></nlm:aff><country xml:lang="fr">Ghana</country><wicri:regionArea>Department of Medicine, Komfo Anokye Teaching Hospital, Kumasi</wicri:regionArea><wicri:noRegion>Kumasi</wicri:noRegion></affiliation><affiliation wicri:level="1"><nlm:aff id="aff2"><addr-line>Department of Medicine, Kwame Nkrumah University of Science and Technology, Kumasi, Ghana</addr-line></nlm:aff><country xml:lang="fr">Ghana</country><wicri:regionArea>Department of Medicine, Kwame Nkrumah University of Science and Technology, Kumasi</wicri:regionArea><wicri:noRegion>Kumasi</wicri:noRegion></affiliation></author><author><name sortKey="Chadwick, David" sort="Chadwick, David" uniqKey="Chadwick D" first="David" last="Chadwick">David Chadwick</name><affiliation wicri:level="1"><nlm:aff id="aff3"><addr-line>Centre for Clinical Infection, The James Cook University Hospital, Middlesbrough, United Kingdom</addr-line></nlm:aff><country xml:lang="fr">Royaume-Uni</country><wicri:regionArea>Centre for Clinical Infection, The James Cook University Hospital, Middlesbrough</wicri:regionArea><wicri:noRegion>Middlesbrough</wicri:noRegion></affiliation></author></analytic><series><title level="j">PLoS ONE</title><idno type="eISSN">1932-6203</idno><imprint><date when="2014">2014</date></imprint></series></biblStruct></sourceDesc></fileDesc><profileDesc><textClass></textClass></profileDesc></teiHeader><front><div type="abstract" xml:lang="en"><p>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/mm<sup>3</sup> 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.</p></div></front><back><div1 type="bibliography"><listBibl><biblStruct></biblStruct><biblStruct></biblStruct><biblStruct></biblStruct><biblStruct><analytic><author><name sortKey="Fellay, J" uniqKey="Fellay J">J Fellay</name></author><author><name sortKey="Boubaker, K" uniqKey="Boubaker K">K Boubaker</name></author><author><name sortKey="Ledergerber, B" uniqKey="Ledergerber B">B Ledergerber</name></author><author><name sortKey="Bernasconi, E" uniqKey="Bernasconi E">E Bernasconi</name></author><author><name sortKey="Furrer, H" uniqKey="Furrer H">H Furrer</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="D Arminio Monteforte, A" uniqKey="D Arminio Monteforte A">A d'Arminio 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<front><journal-meta><journal-id journal-id-type="nlm-ta">PLoS One</journal-id><journal-id journal-id-type="iso-abbrev">PLoS ONE</journal-id><journal-id journal-id-type="publisher-id">plos</journal-id><journal-id journal-id-type="pmc">plosone</journal-id><journal-title-group><journal-title>PLoS ONE</journal-title></journal-title-group><issn pub-type="epub">1932-6203</issn><publisher><publisher-name>Public Library of Science</publisher-name><publisher-loc>San Francisco, USA</publisher-loc></publisher></journal-meta><article-meta><article-id pub-id-type="pmid">24728406</article-id><article-id pub-id-type="pmc">3984248</article-id><article-id pub-id-type="publisher-id">PONE-D-13-51386</article-id><article-id pub-id-type="doi">10.1371/journal.pone.0094854</article-id><article-categories><subj-group subj-group-type="heading"><subject>Research Article</subject></subj-group><subj-group subj-group-type="Discipline-v2"><subject>Biology and Life Sciences</subject><subj-group><subject>Microbiology</subject><subj-group><subject>Medical Microbiology</subject><subj-group><subject>Microbial Pathogens</subject><subj-group><subject>Viral Pathogens</subject><subj-group><subject>Immunodeficiency Viruses</subject><subj-group><subject>HIV</subject></subj-group></subj-group></subj-group></subj-group></subj-group></subj-group></subj-group><subj-group subj-group-type="Discipline-v2"><subject>Medicine and health sciences</subject><subj-group><subject>Diagnostic medicine</subject><subj-group><subject>HIV diagnosis and management</subject></subj-group></subj-group><subj-group><subject>Infectious Diseases</subject><subj-group><subject>Viral Diseases</subject></subj-group></subj-group></subj-group></article-categories><title-group><article-title>Incidence and Determinants of Nevirapine and Efavirenz-Related Skin Rashes in West Africans: Nevirapine's Epitaph?</article-title><alt-title alt-title-type="running-head">NNRTI-Related Skin Rashes in West Africa</alt-title></title-group><contrib-group><contrib contrib-type="author"><name><surname>Sarfo</surname><given-names>Fred Stephen</given-names></name><xref ref-type="aff" rid="aff1"><sup>1</sup></xref><xref ref-type="aff" rid="aff2"><sup>2</sup></xref><xref ref-type="corresp" rid="cor1"><sup>*</sup></xref></contrib><contrib contrib-type="author"><name><surname>Sarfo</surname><given-names>Maame Anima</given-names></name><xref ref-type="aff" rid="aff1"><sup>1</sup></xref></contrib><contrib contrib-type="author"><name><surname>Norman</surname><given-names>Betty</given-names></name><xref ref-type="aff" rid="aff1"><sup>1</sup></xref></contrib><contrib contrib-type="author"><name><surname>Phillips</surname><given-names>Richard</given-names></name><xref ref-type="aff" rid="aff1"><sup>1</sup></xref><xref ref-type="aff" rid="aff2"><sup>2</sup></xref></contrib><contrib contrib-type="author"><name><surname>Chadwick</surname><given-names>David</given-names></name><xref ref-type="aff" rid="aff3"><sup>3</sup></xref></contrib></contrib-group><aff id="aff1"><label>1</label><addr-line>Department of Medicine, Komfo Anokye Teaching Hospital, Kumasi, Ghana</addr-line></aff><aff id="aff2"><label>2</label><addr-line>Department of Medicine, Kwame Nkrumah University of Science and Technology, Kumasi, Ghana</addr-line></aff><aff id="aff3"><label>3</label><addr-line>Centre for Clinical Infection, The James Cook University Hospital, Middlesbrough, United Kingdom</addr-line></aff><contrib-group><contrib contrib-type="editor"><name><surname>Atashili</surname><given-names>Julius</given-names></name><role>Editor</role><xref ref-type="aff" rid="edit1"></xref></contrib></contrib-group><aff id="edit1"><addr-line>University of Buea, Cameroon</addr-line></aff><author-notes><corresp id="cor1">* E-mail: <email>stephensarfo78@gmail.com</email></corresp><fn fn-type="conflict"><p><bold>Competing Interests: </bold>The authors have declared that no competing interests exist.</p></fn><fn fn-type="con"><p>Conceived and designed the experiments: FSS DC. Performed the experiments: FSS MAS BN RP DC. Analyzed the data: FSS DC. Contributed reagents/materials/analysis tools: FSS RP MAS DC. Wrote the paper: FSS DC.</p></fn></author-notes><pub-date pub-type="collection"><year>2014</year></pub-date><pub-date pub-type="epub"><day>11</day><month>4</month><year>2014</year></pub-date><volume>9</volume><issue>4</issue><elocation-id>e94854</elocation-id><history><date date-type="received"><day>9</day><month>12</month><year>2013</year></date><date date-type="accepted"><day>20</day><month>3</month><year>2014</year></date></history><permissions><copyright-year>2014</copyright-year><copyright-holder>Sarfo et al</copyright-holder><license><license-p>This is an open-access article distributed under the terms of the <ext-link ext-link-type="uri" xlink:href="http://creativecommons.org/licenses/by/4.0/">Creative Commons Attribution License</ext-link>, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.</license-p></license></permissions><abstract><p>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/mm<sup>3</sup> 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.</p></abstract><funding-group><funding-statement>This study received financial support via an HIV Research Trust Scholarship to FSS. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.</funding-statement></funding-group><counts><page-count count="7"></page-count></counts></article-meta></front></pmc><affiliations><list><country><li>Ghana</li><li>Royaume-Uni</li></country></list><tree><country name="Ghana"><noRegion><name sortKey="Sarfo, Fred Stephen" sort="Sarfo, Fred Stephen" uniqKey="Sarfo F" first="Fred Stephen" last="Sarfo">Fred Stephen Sarfo</name></noRegion><name sortKey="Norman, Betty" sort="Norman, Betty" uniqKey="Norman B" first="Betty" last="Norman">Betty Norman</name><name sortKey="Phillips, Richard" sort="Phillips, Richard" uniqKey="Phillips R" first="Richard" last="Phillips">Richard Phillips</name><name sortKey="Phillips, Richard" sort="Phillips, Richard" uniqKey="Phillips R" first="Richard" last="Phillips">Richard Phillips</name><name sortKey="Sarfo, Fred Stephen" sort="Sarfo, Fred Stephen" uniqKey="Sarfo F" first="Fred Stephen" last="Sarfo">Fred Stephen Sarfo</name><name sortKey="Sarfo, Maame Anima" sort="Sarfo, Maame Anima" uniqKey="Sarfo M" first="Maame Anima" last="Sarfo">Maame Anima Sarfo</name></country><country name="Royaume-Uni"><noRegion><name sortKey="Chadwick, David" sort="Chadwick, David" uniqKey="Chadwick D" first="David" last="Chadwick">David Chadwick</name></noRegion></country></tree></affiliations></record>Pour manipuler ce document sous Unix (Dilib)
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