Switch to a raltegravir-based regimen versus continuation of a lopinavir-ritonavir-based regimen in stable HIV-infected patients with suppressed viraemia (SWITCHMRK 1 and 2): two multicentre, double-blind, randomised controlled trials
Summary Background To reduce lipid abnormalities and other side-effects associated with antiretroviral regimens containing lopinavir-ritonavir, patients might want to switch one or more components of their regimen. We compared substitution of raltegravir for lopinavir-ritonavir with continuation of...
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| Veröffentlicht in: | The Lancet (British edition) 2010-01, Vol.375 (9712), p.396-407 |
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| creator | Eron, Joseph J, Prof Young, Benjamin, MD Cooper, David A, Prof Youle, Michael, MD DeJesus, Edwin, MD Andrade-Villanueva, Jaime, MD Workman, Cassy, MD Zajdenverg, Roberto, MD Fätkenheuer, Gerd, Prof Berger, Daniel S, MD Kumar, Princy N, MD Rodgers, Anthony J, MS Shaughnessy, Melissa A, MS Walker, Monica L, BS Barnard, Richard JO, PhD Miller, Michael D, PhD DiNubile, Mark J, MD Nguyen, Bach-Yen, MD Leavitt, Randi, MD Xu, Xia, PhD Sklar, Peter, Dr |
| description | Summary Background To reduce lipid abnormalities and other side-effects associated with antiretroviral regimens containing lopinavir-ritonavir, patients might want to switch one or more components of their regimen. We compared substitution of raltegravir for lopinavir-ritonavir with continuation of lopinavir-ritonavir in HIV-infected patients with stable viral suppression on lopinavir-ritonavir-based combination therapy. Methods The SWITCHMRK 1 and 2 studies were multicentre, double-blind, double-dummy, phase 3, randomised controlled trials. HIV-infected patients aged 18 years or older were eligible if they had documented viral RNA (vRNA) concentration below the limit of assay quantification for at least 3 months while on a lopinavir-ritonavir-based regimen. 707 eligible patients were randomly allocated by interactive voice response system in a 1:1 ratio to switch from lopinavir-ritonavir to raltegravir (400 mg twice daily; n=353) or to remain on lopinavir-ritonavir (two 200 mg/50 mg tablets twice daily; n=354), while continuing background therapy consisting of at least two nucleoside or nucleotide reverse transcriptase inhibitors. Primary endpoints were the mean percentage change in serum lipid concentrations from baseline to week 12; the proportion of patients with vRNA concentration less than 50 copies per mL at week 24 (with all treated patients who did not complete the study counted as failures) with a prespecified non-inferiority margin of −12% for each study; and the frequency of adverse events up to 24 weeks. Analyses were done according to protocol. These trials are registered with ClinicalTrials.gov , numbers NCT00443703 and NCT00443729. Findings 702 patients received at least one dose of study drug and were included in the efficacy and safety analyses for the combined trials (raltegravir, n=350; lopinavir-ritonavir, n=352). Percentage changes in lipid concentrations from baseline to week 12 were significantly greater (p |
| doi_str_mv | 10.1016/S0140-6736(09)62041-9 |
| format | Article |
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We compared substitution of raltegravir for lopinavir-ritonavir with continuation of lopinavir-ritonavir in HIV-infected patients with stable viral suppression on lopinavir-ritonavir-based combination therapy. Methods The SWITCHMRK 1 and 2 studies were multicentre, double-blind, double-dummy, phase 3, randomised controlled trials. HIV-infected patients aged 18 years or older were eligible if they had documented viral RNA (vRNA) concentration below the limit of assay quantification for at least 3 months while on a lopinavir-ritonavir-based regimen. 707 eligible patients were randomly allocated by interactive voice response system in a 1:1 ratio to switch from lopinavir-ritonavir to raltegravir (400 mg twice daily; n=353) or to remain on lopinavir-ritonavir (two 200 mg/50 mg tablets twice daily; n=354), while continuing background therapy consisting of at least two nucleoside or nucleotide reverse transcriptase inhibitors. Primary endpoints were the mean percentage change in serum lipid concentrations from baseline to week 12; the proportion of patients with vRNA concentration less than 50 copies per mL at week 24 (with all treated patients who did not complete the study counted as failures) with a prespecified non-inferiority margin of −12% for each study; and the frequency of adverse events up to 24 weeks. Analyses were done according to protocol. These trials are registered with ClinicalTrials.gov , numbers NCT00443703 and NCT00443729. Findings 702 patients received at least one dose of study drug and were included in the efficacy and safety analyses for the combined trials (raltegravir, n=350; lopinavir-ritonavir, n=352). Percentage changes in lipid concentrations from baseline to week 12 were significantly greater (p<0·0001) in the raltegravir group than in the lopinavir-ritonavir group in each study, yielding combined results for total cholesterol −12·6% vs 1·0%, non-HDL cholesterol −15·0% vs 2·6%, and triglycerides −42·2% vs 6·2%. At week 24, 293 (84·4%, 95% CI 80·2–88·1) of 347 patients in the raltegravir group had vRNA concentration less than 50 copies per mL compared with 319 (90·6%, 87·1–93·5) of 352 patients in the lopinavir-ritonavir group (treatment difference −6·2%, −11·2 to −1·3). Clinical and laboratory adverse events occurred at similar frequencies in the treatment groups. There were no serious drug-related adverse events or deaths. The only drug-related clinical adverse event of moderate to severe intensity reported in 1% or more of either treatment group was diarrhoea, which occurred in ten patients in the lopinavir-ritonavir group (3%) and no patients in the raltegravir group. The studies were terminated at week 24 because of lower than expected virological efficacy in the raltegravir group compared with the lopinavir-ritonavir group. Interpretation Although switching to raltegravir was associated with greater reductions in serum lipid concentrations than was continuation of lopinavir-ritonavir, efficacy results did not establish non-inferiority of raltegravir to lopinavir-ritonavir. Funding Merck.</description><identifier>ISSN: 0140-6736</identifier><identifier>EISSN: 1474-547X</identifier><identifier>DOI: 10.1016/S0140-6736(09)62041-9</identifier><identifier>PMID: 20074791</identifier><identifier>CODEN: LANCAO</identifier><language>eng</language><publisher>Kidlington: Elsevier Ltd</publisher><subject>Adult ; Anti-HIV Agents - adverse effects ; Anti-HIV Agents - therapeutic use ; Antibiotics. Antiinfectious agents. Antiparasitic agents ; Antiretroviral agents ; Antiretroviral drugs ; Antiviral agents ; Biological and medical sciences ; Cholesterol ; Cholesterol, LDL - blood ; Cholesterol, LDL - drug effects ; Clinical trials ; Diarrhea ; Double-Blind Method ; Drug Administration Schedule ; Drug therapy ; Drug Therapy, Combination ; Drugs ; Female ; General aspects ; HIV ; HIV Infections - blood ; HIV Infections - drug therapy ; HIV Infections - virology ; HIV-1 - drug effects ; HIV-1 - genetics ; Human immunodeficiency virus ; Human viral diseases ; Humans ; Infectious diseases ; Internal Medicine ; Lipids ; Lopinavir ; Male ; Medical sciences ; Middle Aged ; nucleosides ; Nucleotides ; Pharmacology. Drug treatments ; Pyrimidinones - adverse effects ; Pyrimidinones - therapeutic use ; Pyrrolidinones - adverse effects ; Pyrrolidinones - therapeutic use ; Raltegravir Potassium ; Ritonavir ; Ritonavir - adverse effects ; Ritonavir - therapeutic use ; RNA, Viral - blood ; RNA, Viral - drug effects ; RNA-directed DNA polymerase ; Serum lipids ; Side effects ; Studies ; Tablets ; Treatment Outcome ; Triglycerides ; Viral diseases ; Viral diseases of the lymphoid tissue and the blood. Aids ; Viremia ; Viremia - physiopathology ; Viremia - virology</subject><ispartof>The Lancet (British edition), 2010-01, Vol.375 (9712), p.396-407</ispartof><rights>Elsevier Ltd</rights><rights>2010 Elsevier Ltd</rights><rights>2015 INIST-CNRS</rights><rights>Copyright 2010 Elsevier Ltd. All rights reserved.</rights><rights>Copyright Elsevier Limited Jan 30-Feb 5, 2010</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c509t-f91aff8f28894b17e3cf72177dad4a5ef3422bc336f88ff9cedf0339b0426c8d3</citedby><cites>FETCH-LOGICAL-c509t-f91aff8f28894b17e3cf72177dad4a5ef3422bc336f88ff9cedf0339b0426c8d3</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktohtml>$$Uhttps://www.sciencedirect.com/science/article/pii/S0140673609620419$$EHTML$$P50$$Gelsevier$$H</linktohtml><link.rule.ids>314,776,780,3537,27901,27902,65306</link.rule.ids><backlink>$$Uhttp://pascal-francis.inist.fr/vibad/index.php?action=getRecordDetail&idt=22351365$$DView record in Pascal Francis$$Hfree_for_read</backlink><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/20074791$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Eron, Joseph J, Prof</creatorcontrib><creatorcontrib>Young, Benjamin, MD</creatorcontrib><creatorcontrib>Cooper, David A, Prof</creatorcontrib><creatorcontrib>Youle, Michael, MD</creatorcontrib><creatorcontrib>DeJesus, Edwin, MD</creatorcontrib><creatorcontrib>Andrade-Villanueva, Jaime, MD</creatorcontrib><creatorcontrib>Workman, Cassy, MD</creatorcontrib><creatorcontrib>Zajdenverg, Roberto, MD</creatorcontrib><creatorcontrib>Fätkenheuer, Gerd, Prof</creatorcontrib><creatorcontrib>Berger, Daniel S, MD</creatorcontrib><creatorcontrib>Kumar, Princy N, MD</creatorcontrib><creatorcontrib>Rodgers, Anthony J, MS</creatorcontrib><creatorcontrib>Shaughnessy, Melissa A, MS</creatorcontrib><creatorcontrib>Walker, Monica L, BS</creatorcontrib><creatorcontrib>Barnard, Richard JO, PhD</creatorcontrib><creatorcontrib>Miller, Michael D, PhD</creatorcontrib><creatorcontrib>DiNubile, Mark J, MD</creatorcontrib><creatorcontrib>Nguyen, Bach-Yen, MD</creatorcontrib><creatorcontrib>Leavitt, Randi, MD</creatorcontrib><creatorcontrib>Xu, Xia, PhD</creatorcontrib><creatorcontrib>Sklar, Peter, Dr</creatorcontrib><creatorcontrib>for the SWITCHMRK 1 and 2 investigators</creatorcontrib><creatorcontrib>SWITCHMRK 1 and 2 investigators</creatorcontrib><title>Switch to a raltegravir-based regimen versus continuation of a lopinavir-ritonavir-based regimen in stable HIV-infected patients with suppressed viraemia (SWITCHMRK 1 and 2): two multicentre, double-blind, randomised controlled trials</title><title>The Lancet (British edition)</title><addtitle>Lancet</addtitle><description>Summary Background To reduce lipid abnormalities and other side-effects associated with antiretroviral regimens containing lopinavir-ritonavir, patients might want to switch one or more components of their regimen. We compared substitution of raltegravir for lopinavir-ritonavir with continuation of lopinavir-ritonavir in HIV-infected patients with stable viral suppression on lopinavir-ritonavir-based combination therapy. Methods The SWITCHMRK 1 and 2 studies were multicentre, double-blind, double-dummy, phase 3, randomised controlled trials. HIV-infected patients aged 18 years or older were eligible if they had documented viral RNA (vRNA) concentration below the limit of assay quantification for at least 3 months while on a lopinavir-ritonavir-based regimen. 707 eligible patients were randomly allocated by interactive voice response system in a 1:1 ratio to switch from lopinavir-ritonavir to raltegravir (400 mg twice daily; n=353) or to remain on lopinavir-ritonavir (two 200 mg/50 mg tablets twice daily; n=354), while continuing background therapy consisting of at least two nucleoside or nucleotide reverse transcriptase inhibitors. Primary endpoints were the mean percentage change in serum lipid concentrations from baseline to week 12; the proportion of patients with vRNA concentration less than 50 copies per mL at week 24 (with all treated patients who did not complete the study counted as failures) with a prespecified non-inferiority margin of −12% for each study; and the frequency of adverse events up to 24 weeks. Analyses were done according to protocol. These trials are registered with ClinicalTrials.gov , numbers NCT00443703 and NCT00443729. Findings 702 patients received at least one dose of study drug and were included in the efficacy and safety analyses for the combined trials (raltegravir, n=350; lopinavir-ritonavir, n=352). Percentage changes in lipid concentrations from baseline to week 12 were significantly greater (p<0·0001) in the raltegravir group than in the lopinavir-ritonavir group in each study, yielding combined results for total cholesterol −12·6% vs 1·0%, non-HDL cholesterol −15·0% vs 2·6%, and triglycerides −42·2% vs 6·2%. At week 24, 293 (84·4%, 95% CI 80·2–88·1) of 347 patients in the raltegravir group had vRNA concentration less than 50 copies per mL compared with 319 (90·6%, 87·1–93·5) of 352 patients in the lopinavir-ritonavir group (treatment difference −6·2%, −11·2 to −1·3). Clinical and laboratory adverse events occurred at similar frequencies in the treatment groups. There were no serious drug-related adverse events or deaths. The only drug-related clinical adverse event of moderate to severe intensity reported in 1% or more of either treatment group was diarrhoea, which occurred in ten patients in the lopinavir-ritonavir group (3%) and no patients in the raltegravir group. The studies were terminated at week 24 because of lower than expected virological efficacy in the raltegravir group compared with the lopinavir-ritonavir group. Interpretation Although switching to raltegravir was associated with greater reductions in serum lipid concentrations than was continuation of lopinavir-ritonavir, efficacy results did not establish non-inferiority of raltegravir to lopinavir-ritonavir. Funding Merck.</description><subject>Adult</subject><subject>Anti-HIV Agents - adverse effects</subject><subject>Anti-HIV Agents - therapeutic use</subject><subject>Antibiotics. Antiinfectious agents. Antiparasitic agents</subject><subject>Antiretroviral agents</subject><subject>Antiretroviral drugs</subject><subject>Antiviral agents</subject><subject>Biological and medical sciences</subject><subject>Cholesterol</subject><subject>Cholesterol, LDL - blood</subject><subject>Cholesterol, LDL - drug effects</subject><subject>Clinical trials</subject><subject>Diarrhea</subject><subject>Double-Blind Method</subject><subject>Drug Administration Schedule</subject><subject>Drug therapy</subject><subject>Drug Therapy, Combination</subject><subject>Drugs</subject><subject>Female</subject><subject>General aspects</subject><subject>HIV</subject><subject>HIV Infections - blood</subject><subject>HIV Infections - drug therapy</subject><subject>HIV Infections - virology</subject><subject>HIV-1 - drug effects</subject><subject>HIV-1 - genetics</subject><subject>Human immunodeficiency virus</subject><subject>Human viral diseases</subject><subject>Humans</subject><subject>Infectious diseases</subject><subject>Internal Medicine</subject><subject>Lipids</subject><subject>Lopinavir</subject><subject>Male</subject><subject>Medical sciences</subject><subject>Middle Aged</subject><subject>nucleosides</subject><subject>Nucleotides</subject><subject>Pharmacology. Drug treatments</subject><subject>Pyrimidinones - adverse effects</subject><subject>Pyrimidinones - therapeutic use</subject><subject>Pyrrolidinones - adverse effects</subject><subject>Pyrrolidinones - therapeutic use</subject><subject>Raltegravir Potassium</subject><subject>Ritonavir</subject><subject>Ritonavir - adverse effects</subject><subject>Ritonavir - therapeutic use</subject><subject>RNA, Viral - blood</subject><subject>RNA, Viral - drug effects</subject><subject>RNA-directed DNA polymerase</subject><subject>Serum lipids</subject><subject>Side effects</subject><subject>Studies</subject><subject>Tablets</subject><subject>Treatment Outcome</subject><subject>Triglycerides</subject><subject>Viral diseases</subject><subject>Viral diseases of the lymphoid tissue and the blood. Aids</subject><subject>Viremia</subject><subject>Viremia - physiopathology</subject><subject>Viremia - virology</subject><issn>0140-6736</issn><issn>1474-547X</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2010</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><sourceid>8G5</sourceid><sourceid>BEC</sourceid><sourceid>BENPR</sourceid><sourceid>GUQSH</sourceid><sourceid>M2O</sourceid><recordid>eNqFkmtrFDEUhgdR7Fr9CUoQxC10NJl7_KBIUbtYEVxv30Imc9KmziZjktnSv-yv8Mzu2kIRhUACed_nXJPkIaPPGGXV8yVlBU2rOq_mlB9UGS1Yym8lM1bURVoW9ffbyexKspfcC-GcUlpUtLyb7GWU1kXN2Sz5tbwwUZ2R6IgkXvYRTr1cG5-2MkBHPJyaFViyBh_GQJSz0dhRRuMscRotvRuM3Ri8ic7-xWosCVG2PZDjxdfUWA0q4veAELAxEIx_RsI4DB7C5EOChJWRZL78tvh8dPzh03vCiLQdyQ5ekHjhyGrso1Fo9nBIOjciO217Y7tDrMB2bmUmzpSrd32Pz-iN7MP95I7GCx7s7v3ky9s3GCA9-fhucfT6JFUl5THVnEmtG501DS9aVkOudJ2xuu5kV8gSdF5kWavyvNJNozVX0Gma57ylRVappsv3k6db7uDdzxFCFJiQgr6XFtwYRI2AilPOUTn_p5LRjDYFHobSxzek5270FusQjHNa4sRLFJVbkfIuBA9aDN6spL9Ekpi2Rmy2RkwrISgXm60RUx6PdvCxXUF35fqzJih4shPIoGSvsc3KhGtdlpcsr6YEXm11gP1dG_AiKJwytsh4HLvonPlvKi9vEBRO1mDQH3AJ4bpoETJBt5CJQfmGwPPfxRj3iw</recordid><startdate>20100101</startdate><enddate>20100101</enddate><creator>Eron, Joseph J, Prof</creator><creator>Young, Benjamin, MD</creator><creator>Cooper, David A, Prof</creator><creator>Youle, Michael, MD</creator><creator>DeJesus, Edwin, MD</creator><creator>Andrade-Villanueva, Jaime, MD</creator><creator>Workman, Cassy, MD</creator><creator>Zajdenverg, Roberto, MD</creator><creator>Fätkenheuer, Gerd, Prof</creator><creator>Berger, Daniel S, MD</creator><creator>Kumar, Princy N, MD</creator><creator>Rodgers, Anthony J, MS</creator><creator>Shaughnessy, Melissa A, MS</creator><creator>Walker, Monica L, BS</creator><creator>Barnard, Richard JO, PhD</creator><creator>Miller, Michael D, PhD</creator><creator>DiNubile, Mark J, MD</creator><creator>Nguyen, Bach-Yen, MD</creator><creator>Leavitt, Randi, MD</creator><creator>Xu, Xia, PhD</creator><creator>Sklar, Peter, Dr</creator><general>Elsevier Ltd</general><general>Elsevier</general><general>Elsevier Limited</general><scope>IQODW</scope><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>0TT</scope><scope>0TZ</scope><scope>0U~</scope><scope>3V.</scope><scope>7QL</scope><scope>7QP</scope><scope>7RV</scope><scope>7TK</scope><scope>7U7</scope><scope>7U9</scope><scope>7X7</scope><scope>7XB</scope><scope>88A</scope><scope>88C</scope><scope>88E</scope><scope>88G</scope><scope>88I</scope><scope>8AF</scope><scope>8AO</scope><scope>8C1</scope><scope>8C2</scope><scope>8FE</scope><scope>8FH</scope><scope>8FI</scope><scope>8FJ</scope><scope>8FK</scope><scope>8G5</scope><scope>ABUWG</scope><scope>AEUYN</scope><scope>AFKRA</scope><scope>AN0</scope><scope>ASE</scope><scope>AZQEC</scope><scope>BBNVY</scope><scope>BEC</scope><scope>BENPR</scope><scope>BHPHI</scope><scope>C1K</scope><scope>CCPQU</scope><scope>DWQXO</scope><scope>FPQ</scope><scope>FYUFA</scope><scope>GHDGH</scope><scope>GNUQQ</scope><scope>GUQSH</scope><scope>H94</scope><scope>HCIFZ</scope><scope>K6X</scope><scope>K9-</scope><scope>K9.</scope><scope>KB0</scope><scope>KB~</scope><scope>LK8</scope><scope>M0R</scope><scope>M0S</scope><scope>M0T</scope><scope>M1P</scope><scope>M2M</scope><scope>M2O</scope><scope>M2P</scope><scope>M7N</scope><scope>M7P</scope><scope>MBDVC</scope><scope>NAPCQ</scope><scope>PQEST</scope><scope>PQQKQ</scope><scope>PQUKI</scope><scope>PSYQQ</scope><scope>Q9U</scope><scope>S0X</scope><scope>7X8</scope></search><sort><creationdate>20100101</creationdate><title>Switch to a raltegravir-based regimen versus continuation of a lopinavir-ritonavir-based regimen in stable HIV-infected patients with suppressed viraemia (SWITCHMRK 1 and 2): two multicentre, double-blind, randomised controlled trials</title><author>Eron, Joseph J, Prof ; Young, Benjamin, MD ; Cooper, David A, Prof ; Youle, Michael, MD ; DeJesus, Edwin, MD ; Andrade-Villanueva, Jaime, MD ; Workman, Cassy, MD ; Zajdenverg, Roberto, MD ; Fätkenheuer, Gerd, Prof ; Berger, Daniel S, MD ; Kumar, Princy N, MD ; Rodgers, Anthony J, MS ; Shaughnessy, Melissa A, MS ; Walker, Monica L, BS ; Barnard, Richard JO, PhD ; Miller, Michael D, PhD ; DiNubile, Mark J, MD ; Nguyen, Bach-Yen, MD ; Leavitt, Randi, MD ; Xu, Xia, PhD ; Sklar, Peter, Dr</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c509t-f91aff8f28894b17e3cf72177dad4a5ef3422bc336f88ff9cedf0339b0426c8d3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2010</creationdate><topic>Adult</topic><topic>Anti-HIV Agents - adverse effects</topic><topic>Anti-HIV Agents - therapeutic use</topic><topic>Antibiotics. Antiinfectious agents. Antiparasitic agents</topic><topic>Antiretroviral agents</topic><topic>Antiretroviral drugs</topic><topic>Antiviral agents</topic><topic>Biological and medical sciences</topic><topic>Cholesterol</topic><topic>Cholesterol, LDL - blood</topic><topic>Cholesterol, LDL - drug effects</topic><topic>Clinical trials</topic><topic>Diarrhea</topic><topic>Double-Blind Method</topic><topic>Drug Administration Schedule</topic><topic>Drug therapy</topic><topic>Drug Therapy, Combination</topic><topic>Drugs</topic><topic>Female</topic><topic>General aspects</topic><topic>HIV</topic><topic>HIV Infections - blood</topic><topic>HIV Infections - drug therapy</topic><topic>HIV Infections - virology</topic><topic>HIV-1 - drug effects</topic><topic>HIV-1 - genetics</topic><topic>Human immunodeficiency virus</topic><topic>Human viral diseases</topic><topic>Humans</topic><topic>Infectious diseases</topic><topic>Internal Medicine</topic><topic>Lipids</topic><topic>Lopinavir</topic><topic>Male</topic><topic>Medical sciences</topic><topic>Middle Aged</topic><topic>nucleosides</topic><topic>Nucleotides</topic><topic>Pharmacology. Drug treatments</topic><topic>Pyrimidinones - adverse effects</topic><topic>Pyrimidinones - therapeutic use</topic><topic>Pyrrolidinones - adverse effects</topic><topic>Pyrrolidinones - therapeutic use</topic><topic>Raltegravir Potassium</topic><topic>Ritonavir</topic><topic>Ritonavir - adverse effects</topic><topic>Ritonavir - therapeutic use</topic><topic>RNA, Viral - blood</topic><topic>RNA, Viral - drug effects</topic><topic>RNA-directed DNA polymerase</topic><topic>Serum lipids</topic><topic>Side effects</topic><topic>Studies</topic><topic>Tablets</topic><topic>Treatment Outcome</topic><topic>Triglycerides</topic><topic>Viral diseases</topic><topic>Viral diseases of the lymphoid tissue and the blood. Aids</topic><topic>Viremia</topic><topic>Viremia - physiopathology</topic><topic>Viremia - virology</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Eron, Joseph J, Prof</creatorcontrib><creatorcontrib>Young, Benjamin, MD</creatorcontrib><creatorcontrib>Cooper, David A, Prof</creatorcontrib><creatorcontrib>Youle, Michael, MD</creatorcontrib><creatorcontrib>DeJesus, Edwin, MD</creatorcontrib><creatorcontrib>Andrade-Villanueva, Jaime, MD</creatorcontrib><creatorcontrib>Workman, Cassy, MD</creatorcontrib><creatorcontrib>Zajdenverg, Roberto, MD</creatorcontrib><creatorcontrib>Fätkenheuer, Gerd, Prof</creatorcontrib><creatorcontrib>Berger, Daniel S, MD</creatorcontrib><creatorcontrib>Kumar, Princy N, MD</creatorcontrib><creatorcontrib>Rodgers, Anthony J, MS</creatorcontrib><creatorcontrib>Shaughnessy, Melissa A, MS</creatorcontrib><creatorcontrib>Walker, Monica L, BS</creatorcontrib><creatorcontrib>Barnard, Richard JO, PhD</creatorcontrib><creatorcontrib>Miller, Michael D, PhD</creatorcontrib><creatorcontrib>DiNubile, Mark J, MD</creatorcontrib><creatorcontrib>Nguyen, Bach-Yen, MD</creatorcontrib><creatorcontrib>Leavitt, Randi, MD</creatorcontrib><creatorcontrib>Xu, Xia, PhD</creatorcontrib><creatorcontrib>Sklar, Peter, Dr</creatorcontrib><creatorcontrib>for the SWITCHMRK 1 and 2 investigators</creatorcontrib><creatorcontrib>SWITCHMRK 1 and 2 investigators</creatorcontrib><collection>Pascal-Francis</collection><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>News PRO</collection><collection>Pharma and Biotech Premium PRO</collection><collection>Global News & ABI/Inform Professional</collection><collection>ProQuest Central (Corporate)</collection><collection>Bacteriology Abstracts (Microbiology B)</collection><collection>Calcium & Calcified Tissue Abstracts</collection><collection>ProQuest Nursing and Allied Health Journals</collection><collection>Neurosciences Abstracts</collection><collection>Toxicology Abstracts</collection><collection>Virology and AIDS Abstracts</collection><collection>ProQuest Health and Medical</collection><collection>ProQuest Central (purchase pre-March 2016)</collection><collection>Biology Database (Alumni Edition)</collection><collection>Healthcare Administration Database (Alumni)</collection><collection>Medical Database (Alumni Edition)</collection><collection>Psychology Database (Alumni)</collection><collection>Science Database (Alumni Edition)</collection><collection>STEM Database</collection><collection>ProQuest Pharma Collection</collection><collection>Public Health Database</collection><collection>Lancet Titles</collection><collection>ProQuest SciTech Collection</collection><collection>ProQuest Natural Science 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Present)</collection><collection>Health Research Premium Collection</collection><collection>Health Research Premium Collection (Alumni)</collection><collection>ProQuest Central Student</collection><collection>Research Library Prep</collection><collection>AIDS and Cancer Research Abstracts</collection><collection>SciTech Premium Collection</collection><collection>British Nursing Index</collection><collection>Consumer Health Database (Alumni Edition)</collection><collection>ProQuest Health & Medical Complete (Alumni)</collection><collection>Nursing & Allied Health Database (Alumni Edition)</collection><collection>ProQuest Newsstand Professional</collection><collection>ProQuest Biological Science Collection</collection><collection>Consumer Health Database</collection><collection>Health & Medical Collection (Alumni Edition)</collection><collection>ProQuest Health Management</collection><collection>Medical Database</collection><collection>ProQuest Psychology</collection><collection>ProQuest Research Library</collection><collection>ProQuest Science Journals</collection><collection>Algology Mycology and Protozoology Abstracts (Microbiology C)</collection><collection>ProQuest Biological Science Journals</collection><collection>Research Library (Corporate)</collection><collection>Nursing & Allied Health Premium</collection><collection>ProQuest One Academic Eastern Edition (DO NOT USE)</collection><collection>ProQuest One Academic</collection><collection>ProQuest One Academic UKI Edition</collection><collection>ProQuest One Psychology</collection><collection>ProQuest Central Basic</collection><collection>SIRS Editorial</collection><collection>MEDLINE - Academic</collection><jtitle>The Lancet (British edition)</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Eron, Joseph J, Prof</au><au>Young, Benjamin, MD</au><au>Cooper, David A, Prof</au><au>Youle, Michael, MD</au><au>DeJesus, Edwin, MD</au><au>Andrade-Villanueva, Jaime, MD</au><au>Workman, Cassy, MD</au><au>Zajdenverg, Roberto, MD</au><au>Fätkenheuer, Gerd, Prof</au><au>Berger, Daniel S, MD</au><au>Kumar, Princy N, MD</au><au>Rodgers, Anthony J, MS</au><au>Shaughnessy, Melissa A, MS</au><au>Walker, Monica L, BS</au><au>Barnard, Richard JO, PhD</au><au>Miller, Michael D, PhD</au><au>DiNubile, Mark J, MD</au><au>Nguyen, Bach-Yen, MD</au><au>Leavitt, Randi, MD</au><au>Xu, Xia, PhD</au><au>Sklar, Peter, Dr</au><aucorp>for the SWITCHMRK 1 and 2 investigators</aucorp><aucorp>SWITCHMRK 1 and 2 investigators</aucorp><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Switch to a raltegravir-based regimen versus continuation of a lopinavir-ritonavir-based regimen in stable HIV-infected patients with suppressed viraemia (SWITCHMRK 1 and 2): two multicentre, double-blind, randomised controlled trials</atitle><jtitle>The Lancet (British edition)</jtitle><addtitle>Lancet</addtitle><date>2010-01-01</date><risdate>2010</risdate><volume>375</volume><issue>9712</issue><spage>396</spage><epage>407</epage><pages>396-407</pages><issn>0140-6736</issn><eissn>1474-547X</eissn><coden>LANCAO</coden><abstract>Summary Background To reduce lipid abnormalities and other side-effects associated with antiretroviral regimens containing lopinavir-ritonavir, patients might want to switch one or more components of their regimen. We compared substitution of raltegravir for lopinavir-ritonavir with continuation of lopinavir-ritonavir in HIV-infected patients with stable viral suppression on lopinavir-ritonavir-based combination therapy. Methods The SWITCHMRK 1 and 2 studies were multicentre, double-blind, double-dummy, phase 3, randomised controlled trials. HIV-infected patients aged 18 years or older were eligible if they had documented viral RNA (vRNA) concentration below the limit of assay quantification for at least 3 months while on a lopinavir-ritonavir-based regimen. 707 eligible patients were randomly allocated by interactive voice response system in a 1:1 ratio to switch from lopinavir-ritonavir to raltegravir (400 mg twice daily; n=353) or to remain on lopinavir-ritonavir (two 200 mg/50 mg tablets twice daily; n=354), while continuing background therapy consisting of at least two nucleoside or nucleotide reverse transcriptase inhibitors. Primary endpoints were the mean percentage change in serum lipid concentrations from baseline to week 12; the proportion of patients with vRNA concentration less than 50 copies per mL at week 24 (with all treated patients who did not complete the study counted as failures) with a prespecified non-inferiority margin of −12% for each study; and the frequency of adverse events up to 24 weeks. Analyses were done according to protocol. These trials are registered with ClinicalTrials.gov , numbers NCT00443703 and NCT00443729. Findings 702 patients received at least one dose of study drug and were included in the efficacy and safety analyses for the combined trials (raltegravir, n=350; lopinavir-ritonavir, n=352). Percentage changes in lipid concentrations from baseline to week 12 were significantly greater (p<0·0001) in the raltegravir group than in the lopinavir-ritonavir group in each study, yielding combined results for total cholesterol −12·6% vs 1·0%, non-HDL cholesterol −15·0% vs 2·6%, and triglycerides −42·2% vs 6·2%. At week 24, 293 (84·4%, 95% CI 80·2–88·1) of 347 patients in the raltegravir group had vRNA concentration less than 50 copies per mL compared with 319 (90·6%, 87·1–93·5) of 352 patients in the lopinavir-ritonavir group (treatment difference −6·2%, −11·2 to −1·3). Clinical and laboratory adverse events occurred at similar frequencies in the treatment groups. There were no serious drug-related adverse events or deaths. The only drug-related clinical adverse event of moderate to severe intensity reported in 1% or more of either treatment group was diarrhoea, which occurred in ten patients in the lopinavir-ritonavir group (3%) and no patients in the raltegravir group. The studies were terminated at week 24 because of lower than expected virological efficacy in the raltegravir group compared with the lopinavir-ritonavir group. Interpretation Although switching to raltegravir was associated with greater reductions in serum lipid concentrations than was continuation of lopinavir-ritonavir, efficacy results did not establish non-inferiority of raltegravir to lopinavir-ritonavir. Funding Merck.</abstract><cop>Kidlington</cop><pub>Elsevier Ltd</pub><pmid>20074791</pmid><doi>10.1016/S0140-6736(09)62041-9</doi><tpages>12</tpages></addata></record> |
| fulltext | fulltext |
| identifier | ISSN: 0140-6736 |
| ispartof | The Lancet (British edition), 2010-01, Vol.375 (9712), p.396-407 |
| issn | 0140-6736 1474-547X |
| language | eng |
| recordid | cdi_proquest_miscellaneous_734269099 |
| source | MEDLINE; Elsevier ScienceDirect Journals |
| subjects | Adult Anti-HIV Agents - adverse effects Anti-HIV Agents - therapeutic use Antibiotics. Antiinfectious agents. Antiparasitic agents Antiretroviral agents Antiretroviral drugs Antiviral agents Biological and medical sciences Cholesterol Cholesterol, LDL - blood Cholesterol, LDL - drug effects Clinical trials Diarrhea Double-Blind Method Drug Administration Schedule Drug therapy Drug Therapy, Combination Drugs Female General aspects HIV HIV Infections - blood HIV Infections - drug therapy HIV Infections - virology HIV-1 - drug effects HIV-1 - genetics Human immunodeficiency virus Human viral diseases Humans Infectious diseases Internal Medicine Lipids Lopinavir Male Medical sciences Middle Aged nucleosides Nucleotides Pharmacology. Drug treatments Pyrimidinones - adverse effects Pyrimidinones - therapeutic use Pyrrolidinones - adverse effects Pyrrolidinones - therapeutic use Raltegravir Potassium Ritonavir Ritonavir - adverse effects Ritonavir - therapeutic use RNA, Viral - blood RNA, Viral - drug effects RNA-directed DNA polymerase Serum lipids Side effects Studies Tablets Treatment Outcome Triglycerides Viral diseases Viral diseases of the lymphoid tissue and the blood. Aids Viremia Viremia - physiopathology Viremia - virology |
| title | Switch to a raltegravir-based regimen versus continuation of a lopinavir-ritonavir-based regimen in stable HIV-infected patients with suppressed viraemia (SWITCHMRK 1 and 2): two multicentre, double-blind, randomised controlled trials |
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