Characterization of associations and development of atazanavir resistance after unplanned treatment interruptions
Objectives Although current guidelines recommend resistance testing prior to antiretroviral therapy (ART) reinitiation after treatment interruptions, virological failure of first‐line ritonavir‐boosted, protease‐inhibitor (PI/r)‐containing ART is associated with low emergent PI resistance. In patien...
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| Veröffentlicht in: | HIV medicine 2014-04, Vol.15 (4), p.224-232 |
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| creator | Tinago, W O'Halloran, JA O'Halloran, RM Macken, A Lambert, JS Sheehan, GJ Mallon, PWG |
| description | Objectives
Although current guidelines recommend resistance testing prior to antiretroviral therapy (ART) reinitiation after treatment interruptions, virological failure of first‐line ritonavir‐boosted, protease‐inhibitor (PI/r)‐containing ART is associated with low emergent PI resistance. In patients experiencing unscheduled treatment interruptions (UTrIs) on ritonavir‐boosted atazanavir (ATV/r) ART regimens, we hypothesized low emergence of PI mutations conferring resistance to ATV/r.
Methods
In a retrospective assessment of HIV‐infected patients initiating ATV/r‐containing ART, using logistic regression we determined factors associated with UTrI, the prevalence of emergent resistance mutations and virological response after ART reinitiation.
Results
A total of 202 patients [median age 33 years (interquartile range (IQR) 29–40 years); 52% female; median CD4 count 184 cells/μL (IQR 107–280 cells/μL); median HIV RNA 4.6 log10 HIV‐1 RNA copies/mL (IQR 3.2–5.1 copies/mL)] initiated ATV/r between 2004 and 2009; 80 (43%) were ART naïve. One hundred and ten patients (55%) underwent 195 UTrIs after a median (IQR) 25 (10–52) weeks on ART, with a median (IQR) UTrI duration of 10 (3–31) weeks. Fifty‐four of 110 patients (49%) underwent more than one UTrI. The commonest reasons for UTrI were nonadherence (52.7%) and drug intolerance (20%). Baseline HIV RNA > 100 000 copies\mL [odds ratio (OR) 3.6; 95% confidence interval (CI) 1.3–9.95] and being HCV positive, an injecting drug user or on methadone (OR 2.4; 95% CI 1.3–4.4) were independently associated with UTrI. In 39 patients with at least two resistance assays during UTrIs, 72 new mutations emerged; four nucleoside reverse transcriptase inhibitor (NRTI), two nonnucleoside reverse transcriptase inhibitor (NNRTI) and 66 protease inhibitor (PI) resistance mutations. All emergent PI resistance mutations were minor mutations. At least 65% of patients were re‐suppressed on ATV/r reinitiation.
Conclusions
In this PI‐treated cohort, UTrIs are common. All emergent PI resistance mutations were minor and ATV/r retained activity and efficacy when reintroduced, even after several UTrIs, raising questions regarding the need for routine genotypic resistance assays in PI/r‐treated patients prior to ART reinitiation after UTrI. |
| doi_str_mv | 10.1111/hiv.12107 |
| format | Article |
| fullrecord | <record><control><sourceid>proquest_cross</sourceid><recordid>TN_cdi_proquest_miscellaneous_1504143543</recordid><sourceformat>XML</sourceformat><sourcesystem>PC</sourcesystem><sourcerecordid>1504143543</sourcerecordid><originalsourceid>FETCH-LOGICAL-c3257-a2697598815aaa91caa7cd232eeb2edf5f3faab447451ee5e639ca8ce07a57143</originalsourceid><addsrcrecordid>eNp1kL1OwzAURi0EglIYeAGUEYa0_o2bEVVAkZBYgDW6dW5Uo9RJ7aSofXpMCmzcxdf6jo-sj5ArRicsznRltxPGGdVHZMRkNksZz8XxsMuUZxk_I-chfFDKtMjpKTnjkjMlNB2RzXwFHkyH3u6hs41LmiqBEBpjh2tIwJVJiVusm3aNrhvyDvbgYGt94jHY0IEzmEAVLUnv2hqcwzLpPEI3PLEuJr5vB-EFOamgDnj5c47J28P963yRPr88Ps3vnlMjuNIp8CzXKp_NmAKAnBkAbUouOOKSY1mpSlQASym1VAxRYSZyAzODVIPSTIoxuTl4W99segxdsbbBYB1_h00fCqaojJiSIqK3B9T4JgSPVdF6uwa_KxgtvhsuYsPF0HBkr3-0_XKN5R_5W2kEpgfg09a4-99ULJ7eD8ov5yWI1w</addsrcrecordid><sourcetype>Aggregation Database</sourcetype><iscdi>true</iscdi><recordtype>article</recordtype><pqid>1504143543</pqid></control><display><type>article</type><title>Characterization of associations and development of atazanavir resistance after unplanned treatment interruptions</title><source>MEDLINE</source><source>Wiley Free Content</source><source>EZB-FREE-00999 freely available EZB journals</source><source>Wiley Online Library All Journals</source><creator>Tinago, W ; O'Halloran, JA ; O'Halloran, RM ; Macken, A ; Lambert, JS ; Sheehan, GJ ; Mallon, PWG</creator><creatorcontrib>Tinago, W ; O'Halloran, JA ; O'Halloran, RM ; Macken, A ; Lambert, JS ; Sheehan, GJ ; Mallon, PWG</creatorcontrib><description>Objectives
Although current guidelines recommend resistance testing prior to antiretroviral therapy (ART) reinitiation after treatment interruptions, virological failure of first‐line ritonavir‐boosted, protease‐inhibitor (PI/r)‐containing ART is associated with low emergent PI resistance. In patients experiencing unscheduled treatment interruptions (UTrIs) on ritonavir‐boosted atazanavir (ATV/r) ART regimens, we hypothesized low emergence of PI mutations conferring resistance to ATV/r.
Methods
In a retrospective assessment of HIV‐infected patients initiating ATV/r‐containing ART, using logistic regression we determined factors associated with UTrI, the prevalence of emergent resistance mutations and virological response after ART reinitiation.
Results
A total of 202 patients [median age 33 years (interquartile range (IQR) 29–40 years); 52% female; median CD4 count 184 cells/μL (IQR 107–280 cells/μL); median HIV RNA 4.6 log10 HIV‐1 RNA copies/mL (IQR 3.2–5.1 copies/mL)] initiated ATV/r between 2004 and 2009; 80 (43%) were ART naïve. One hundred and ten patients (55%) underwent 195 UTrIs after a median (IQR) 25 (10–52) weeks on ART, with a median (IQR) UTrI duration of 10 (3–31) weeks. Fifty‐four of 110 patients (49%) underwent more than one UTrI. The commonest reasons for UTrI were nonadherence (52.7%) and drug intolerance (20%). Baseline HIV RNA > 100 000 copies\mL [odds ratio (OR) 3.6; 95% confidence interval (CI) 1.3–9.95] and being HCV positive, an injecting drug user or on methadone (OR 2.4; 95% CI 1.3–4.4) were independently associated with UTrI. In 39 patients with at least two resistance assays during UTrIs, 72 new mutations emerged; four nucleoside reverse transcriptase inhibitor (NRTI), two nonnucleoside reverse transcriptase inhibitor (NNRTI) and 66 protease inhibitor (PI) resistance mutations. All emergent PI resistance mutations were minor mutations. At least 65% of patients were re‐suppressed on ATV/r reinitiation.
Conclusions
In this PI‐treated cohort, UTrIs are common. All emergent PI resistance mutations were minor and ATV/r retained activity and efficacy when reintroduced, even after several UTrIs, raising questions regarding the need for routine genotypic resistance assays in PI/r‐treated patients prior to ART reinitiation after UTrI.</description><identifier>ISSN: 1464-2662</identifier><identifier>EISSN: 1468-1293</identifier><identifier>DOI: 10.1111/hiv.12107</identifier><identifier>PMID: 24215370</identifier><language>eng</language><publisher>England</publisher><subject>Adult ; Anti-HIV Agents - administration & dosage ; Atazanavir Sulfate ; Cohort Studies ; Drug Resistance, Viral ; Female ; Genes, Viral ; genotypic resistance ; HIV - drug effects ; HIV - genetics ; HIV Infections - drug therapy ; HIV Infections - virology ; HIV Protease Inhibitors - administration & dosage ; Humans ; Male ; Medication Adherence ; Mutation ; Oligopeptides - administration & dosage ; protease inhibitor mutations ; Pyridines - administration & dosage ; Retrospective Studies ; Risk Factors ; Ritonavir - administration & dosage ; unscheduled treatment interruptions ; Viral Load ; viral supression</subject><ispartof>HIV medicine, 2014-04, Vol.15 (4), p.224-232</ispartof><rights>2013 British HIV Association</rights><rights>2013 British HIV Association.</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c3257-a2697598815aaa91caa7cd232eeb2edf5f3faab447451ee5e639ca8ce07a57143</citedby><cites>FETCH-LOGICAL-c3257-a2697598815aaa91caa7cd232eeb2edf5f3faab447451ee5e639ca8ce07a57143</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://onlinelibrary.wiley.com/doi/pdf/10.1111%2Fhiv.12107$$EPDF$$P50$$Gwiley$$H</linktopdf><linktohtml>$$Uhttps://onlinelibrary.wiley.com/doi/full/10.1111%2Fhiv.12107$$EHTML$$P50$$Gwiley$$H</linktohtml><link.rule.ids>314,780,784,1416,1432,27923,27924,45573,45574,46408,46832</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/24215370$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Tinago, W</creatorcontrib><creatorcontrib>O'Halloran, JA</creatorcontrib><creatorcontrib>O'Halloran, RM</creatorcontrib><creatorcontrib>Macken, A</creatorcontrib><creatorcontrib>Lambert, JS</creatorcontrib><creatorcontrib>Sheehan, GJ</creatorcontrib><creatorcontrib>Mallon, PWG</creatorcontrib><title>Characterization of associations and development of atazanavir resistance after unplanned treatment interruptions</title><title>HIV medicine</title><addtitle>HIV Med</addtitle><description>Objectives
Although current guidelines recommend resistance testing prior to antiretroviral therapy (ART) reinitiation after treatment interruptions, virological failure of first‐line ritonavir‐boosted, protease‐inhibitor (PI/r)‐containing ART is associated with low emergent PI resistance. In patients experiencing unscheduled treatment interruptions (UTrIs) on ritonavir‐boosted atazanavir (ATV/r) ART regimens, we hypothesized low emergence of PI mutations conferring resistance to ATV/r.
Methods
In a retrospective assessment of HIV‐infected patients initiating ATV/r‐containing ART, using logistic regression we determined factors associated with UTrI, the prevalence of emergent resistance mutations and virological response after ART reinitiation.
Results
A total of 202 patients [median age 33 years (interquartile range (IQR) 29–40 years); 52% female; median CD4 count 184 cells/μL (IQR 107–280 cells/μL); median HIV RNA 4.6 log10 HIV‐1 RNA copies/mL (IQR 3.2–5.1 copies/mL)] initiated ATV/r between 2004 and 2009; 80 (43%) were ART naïve. One hundred and ten patients (55%) underwent 195 UTrIs after a median (IQR) 25 (10–52) weeks on ART, with a median (IQR) UTrI duration of 10 (3–31) weeks. Fifty‐four of 110 patients (49%) underwent more than one UTrI. The commonest reasons for UTrI were nonadherence (52.7%) and drug intolerance (20%). Baseline HIV RNA > 100 000 copies\mL [odds ratio (OR) 3.6; 95% confidence interval (CI) 1.3–9.95] and being HCV positive, an injecting drug user or on methadone (OR 2.4; 95% CI 1.3–4.4) were independently associated with UTrI. In 39 patients with at least two resistance assays during UTrIs, 72 new mutations emerged; four nucleoside reverse transcriptase inhibitor (NRTI), two nonnucleoside reverse transcriptase inhibitor (NNRTI) and 66 protease inhibitor (PI) resistance mutations. All emergent PI resistance mutations were minor mutations. At least 65% of patients were re‐suppressed on ATV/r reinitiation.
Conclusions
In this PI‐treated cohort, UTrIs are common. All emergent PI resistance mutations were minor and ATV/r retained activity and efficacy when reintroduced, even after several UTrIs, raising questions regarding the need for routine genotypic resistance assays in PI/r‐treated patients prior to ART reinitiation after UTrI.</description><subject>Adult</subject><subject>Anti-HIV Agents - administration & dosage</subject><subject>Atazanavir Sulfate</subject><subject>Cohort Studies</subject><subject>Drug Resistance, Viral</subject><subject>Female</subject><subject>Genes, Viral</subject><subject>genotypic resistance</subject><subject>HIV - drug effects</subject><subject>HIV - genetics</subject><subject>HIV Infections - drug therapy</subject><subject>HIV Infections - virology</subject><subject>HIV Protease Inhibitors - administration & dosage</subject><subject>Humans</subject><subject>Male</subject><subject>Medication Adherence</subject><subject>Mutation</subject><subject>Oligopeptides - administration & dosage</subject><subject>protease inhibitor mutations</subject><subject>Pyridines - administration & dosage</subject><subject>Retrospective Studies</subject><subject>Risk Factors</subject><subject>Ritonavir - administration & dosage</subject><subject>unscheduled treatment interruptions</subject><subject>Viral Load</subject><subject>viral supression</subject><issn>1464-2662</issn><issn>1468-1293</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2014</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNp1kL1OwzAURi0EglIYeAGUEYa0_o2bEVVAkZBYgDW6dW5Uo9RJ7aSofXpMCmzcxdf6jo-sj5ArRicsznRltxPGGdVHZMRkNksZz8XxsMuUZxk_I-chfFDKtMjpKTnjkjMlNB2RzXwFHkyH3u6hs41LmiqBEBpjh2tIwJVJiVusm3aNrhvyDvbgYGt94jHY0IEzmEAVLUnv2hqcwzLpPEI3PLEuJr5vB-EFOamgDnj5c47J28P963yRPr88Ps3vnlMjuNIp8CzXKp_NmAKAnBkAbUouOOKSY1mpSlQASym1VAxRYSZyAzODVIPSTIoxuTl4W99segxdsbbBYB1_h00fCqaojJiSIqK3B9T4JgSPVdF6uwa_KxgtvhsuYsPF0HBkr3-0_XKN5R_5W2kEpgfg09a4-99ULJ7eD8ov5yWI1w</recordid><startdate>201404</startdate><enddate>201404</enddate><creator>Tinago, W</creator><creator>O'Halloran, JA</creator><creator>O'Halloran, RM</creator><creator>Macken, A</creator><creator>Lambert, JS</creator><creator>Sheehan, GJ</creator><creator>Mallon, PWG</creator><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>7X8</scope></search><sort><creationdate>201404</creationdate><title>Characterization of associations and development of atazanavir resistance after unplanned treatment interruptions</title><author>Tinago, W ; O'Halloran, JA ; O'Halloran, RM ; Macken, A ; Lambert, JS ; Sheehan, GJ ; Mallon, PWG</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c3257-a2697598815aaa91caa7cd232eeb2edf5f3faab447451ee5e639ca8ce07a57143</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2014</creationdate><topic>Adult</topic><topic>Anti-HIV Agents - administration & dosage</topic><topic>Atazanavir Sulfate</topic><topic>Cohort Studies</topic><topic>Drug Resistance, Viral</topic><topic>Female</topic><topic>Genes, Viral</topic><topic>genotypic resistance</topic><topic>HIV - drug effects</topic><topic>HIV - genetics</topic><topic>HIV Infections - drug therapy</topic><topic>HIV Infections - virology</topic><topic>HIV Protease Inhibitors - administration & dosage</topic><topic>Humans</topic><topic>Male</topic><topic>Medication Adherence</topic><topic>Mutation</topic><topic>Oligopeptides - administration & dosage</topic><topic>protease inhibitor mutations</topic><topic>Pyridines - administration & dosage</topic><topic>Retrospective Studies</topic><topic>Risk Factors</topic><topic>Ritonavir - administration & dosage</topic><topic>unscheduled treatment interruptions</topic><topic>Viral Load</topic><topic>viral supression</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Tinago, W</creatorcontrib><creatorcontrib>O'Halloran, JA</creatorcontrib><creatorcontrib>O'Halloran, RM</creatorcontrib><creatorcontrib>Macken, A</creatorcontrib><creatorcontrib>Lambert, JS</creatorcontrib><creatorcontrib>Sheehan, GJ</creatorcontrib><creatorcontrib>Mallon, PWG</creatorcontrib><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>MEDLINE - Academic</collection><jtitle>HIV medicine</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Tinago, W</au><au>O'Halloran, JA</au><au>O'Halloran, RM</au><au>Macken, A</au><au>Lambert, JS</au><au>Sheehan, GJ</au><au>Mallon, PWG</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Characterization of associations and development of atazanavir resistance after unplanned treatment interruptions</atitle><jtitle>HIV medicine</jtitle><addtitle>HIV Med</addtitle><date>2014-04</date><risdate>2014</risdate><volume>15</volume><issue>4</issue><spage>224</spage><epage>232</epage><pages>224-232</pages><issn>1464-2662</issn><eissn>1468-1293</eissn><abstract>Objectives
Although current guidelines recommend resistance testing prior to antiretroviral therapy (ART) reinitiation after treatment interruptions, virological failure of first‐line ritonavir‐boosted, protease‐inhibitor (PI/r)‐containing ART is associated with low emergent PI resistance. In patients experiencing unscheduled treatment interruptions (UTrIs) on ritonavir‐boosted atazanavir (ATV/r) ART regimens, we hypothesized low emergence of PI mutations conferring resistance to ATV/r.
Methods
In a retrospective assessment of HIV‐infected patients initiating ATV/r‐containing ART, using logistic regression we determined factors associated with UTrI, the prevalence of emergent resistance mutations and virological response after ART reinitiation.
Results
A total of 202 patients [median age 33 years (interquartile range (IQR) 29–40 years); 52% female; median CD4 count 184 cells/μL (IQR 107–280 cells/μL); median HIV RNA 4.6 log10 HIV‐1 RNA copies/mL (IQR 3.2–5.1 copies/mL)] initiated ATV/r between 2004 and 2009; 80 (43%) were ART naïve. One hundred and ten patients (55%) underwent 195 UTrIs after a median (IQR) 25 (10–52) weeks on ART, with a median (IQR) UTrI duration of 10 (3–31) weeks. Fifty‐four of 110 patients (49%) underwent more than one UTrI. The commonest reasons for UTrI were nonadherence (52.7%) and drug intolerance (20%). Baseline HIV RNA > 100 000 copies\mL [odds ratio (OR) 3.6; 95% confidence interval (CI) 1.3–9.95] and being HCV positive, an injecting drug user or on methadone (OR 2.4; 95% CI 1.3–4.4) were independently associated with UTrI. In 39 patients with at least two resistance assays during UTrIs, 72 new mutations emerged; four nucleoside reverse transcriptase inhibitor (NRTI), two nonnucleoside reverse transcriptase inhibitor (NNRTI) and 66 protease inhibitor (PI) resistance mutations. All emergent PI resistance mutations were minor mutations. At least 65% of patients were re‐suppressed on ATV/r reinitiation.
Conclusions
In this PI‐treated cohort, UTrIs are common. All emergent PI resistance mutations were minor and ATV/r retained activity and efficacy when reintroduced, even after several UTrIs, raising questions regarding the need for routine genotypic resistance assays in PI/r‐treated patients prior to ART reinitiation after UTrI.</abstract><cop>England</cop><pmid>24215370</pmid><doi>10.1111/hiv.12107</doi><tpages>9</tpages></addata></record> |
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| ispartof | HIV medicine, 2014-04, Vol.15 (4), p.224-232 |
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| subjects | Adult Anti-HIV Agents - administration & dosage Atazanavir Sulfate Cohort Studies Drug Resistance, Viral Female Genes, Viral genotypic resistance HIV - drug effects HIV - genetics HIV Infections - drug therapy HIV Infections - virology HIV Protease Inhibitors - administration & dosage Humans Male Medication Adherence Mutation Oligopeptides - administration & dosage protease inhibitor mutations Pyridines - administration & dosage Retrospective Studies Risk Factors Ritonavir - administration & dosage unscheduled treatment interruptions Viral Load viral supression |
| title | Characterization of associations and development of atazanavir resistance after unplanned treatment interruptions |
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