Efficacy and safety of darunavir-ritonavir compared with that of lopinavir-ritonavir at 48 weeks in treatment-experienced, HIV-infected patients in TITAN: a randomised controlled phase III trial
Summary Background The protease inhibitor darunavir has been shown to be efficacious in highly treatment-experienced patients with HIV infection, but needs to be assessed in patients with a broader range of treatment experience. We did a randomised, controlled, phase III trial (TITAN) to compare 48-...
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| Veröffentlicht in: | The Lancet (British edition) 2007-07, Vol.370 (9581), p.49-58 |
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| creator | Madruga, José Valdez, Dr Berger, Daniel, MD McMurchie, Marilyn, MD Suter, Fredy, MD Banhegyi, Denes, MD Ruxrungtham, Kiat, MD Norris, Dorece, MD Lefebvre, Eric, MD de Béthune, Marie-Pierre, PhD Tomaka, Frank, MD De Pauw, Martine, PharmD Vangeneugden, Tony, MSc Spinosa-Guzman, Sabrina, MD |
| description | Summary Background The protease inhibitor darunavir has been shown to be efficacious in highly treatment-experienced patients with HIV infection, but needs to be assessed in patients with a broader range of treatment experience. We did a randomised, controlled, phase III trial (TITAN) to compare 48-week efficacy and safety of darunavir-ritonavir with that of lopinavir-ritonavir in treatment-experienced, lopinavir-naive patients. Methods Patients received optimised background regimen plus non-blinded treatment with darunavir-ritonavir 600/100 mg twice daily or lopinavir-ritonavir 400/100 mg twice daily. The primary endpoint was non-inferiority (95% CI lower limit for the difference in treatment response −12% or greater) for HIV RNA of less than 400 copies per mL in plasma at week 48 (per-protocol analysis). TITAN (TMC114-C214) is registered with ClinicalTrials.gov , number NCT00110877. Findings Of 595 patients randomised and treated, 187 (31%) were protease inhibitor naive; 476 of 582 (82%) were susceptible to four or more protease inhibitors. At week 48, significantly more darunavir-ritonavir than lopinavir-ritonavir patients had HIV RNA of less than 400 copies per mL (77% [220 of 286] vs 68% [199 of 293]; estimated difference 9%, 95% CI 2–16). Fewer virological failures treated with darunavir-ritonavir than with lopinavir-ritonavir developed primary protease inhibitor mutations (21% [n=6] vs 36% [n=20]) and nucleoside analogue-associated mutations (14% [n=4] vs 27% [n=15]). Safety data were generally similar between the groups; grade 3 or 4 adverse events occurred in 80 (27%) darunavir-ritonavir and 89 (30%) lopinavir-ritonavir patients. Interpretation In lopinavir-naive, treatment-experienced patients, darunavir-ritonavir was non-inferior to lopinavir-ritonavir treatment in terms of our virological endpoint, and should therefore be considered as a treatment option for this population. |
| doi_str_mv | 10.1016/S0140-6736(07)61049-6 |
| format | Article |
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We did a randomised, controlled, phase III trial (TITAN) to compare 48-week efficacy and safety of darunavir-ritonavir with that of lopinavir-ritonavir in treatment-experienced, lopinavir-naive patients. Methods Patients received optimised background regimen plus non-blinded treatment with darunavir-ritonavir 600/100 mg twice daily or lopinavir-ritonavir 400/100 mg twice daily. The primary endpoint was non-inferiority (95% CI lower limit for the difference in treatment response −12% or greater) for HIV RNA of less than 400 copies per mL in plasma at week 48 (per-protocol analysis). TITAN (TMC114-C214) is registered with ClinicalTrials.gov , number NCT00110877. Findings Of 595 patients randomised and treated, 187 (31%) were protease inhibitor naive; 476 of 582 (82%) were susceptible to four or more protease inhibitors. At week 48, significantly more darunavir-ritonavir than lopinavir-ritonavir patients had HIV RNA of less than 400 copies per mL (77% [220 of 286] vs 68% [199 of 293]; estimated difference 9%, 95% CI 2–16). Fewer virological failures treated with darunavir-ritonavir than with lopinavir-ritonavir developed primary protease inhibitor mutations (21% [n=6] vs 36% [n=20]) and nucleoside analogue-associated mutations (14% [n=4] vs 27% [n=15]). Safety data were generally similar between the groups; grade 3 or 4 adverse events occurred in 80 (27%) darunavir-ritonavir and 89 (30%) lopinavir-ritonavir patients. Interpretation In lopinavir-naive, treatment-experienced patients, darunavir-ritonavir was non-inferior to lopinavir-ritonavir treatment in terms of our virological endpoint, and should therefore be considered as a treatment option for this population.</description><identifier>ISSN: 0140-6736</identifier><identifier>EISSN: 1474-547X</identifier><identifier>DOI: 10.1016/S0140-6736(07)61049-6</identifier><identifier>PMID: 17617272</identifier><identifier>CODEN: LANCAO</identifier><language>eng</language><publisher>England: Elsevier Ltd</publisher><subject>Adult ; Antiretroviral drugs ; Antiretroviral Therapy, Highly Active ; Clinical trials ; Darunavir ; Drug therapy ; Female ; HIV ; HIV Infections - drug therapy ; HIV Protease Inhibitors - adverse effects ; HIV Protease Inhibitors - therapeutic use ; HIV-1 - drug effects ; Human immunodeficiency virus ; Humans ; Internal Medicine ; Kaposis sarcoma ; Lopinavir ; Male ; Middle Aged ; Mutation ; Patients ; Product safety ; Proteinase inhibitors ; Pyrimidinones - adverse effects ; Pyrimidinones - therapeutic use ; Ritonavir ; Ritonavir - adverse effects ; Ritonavir - therapeutic use ; RNA, Viral - blood ; Safety ; Sulfonamides - adverse effects ; Sulfonamides - therapeutic use</subject><ispartof>The Lancet (British edition), 2007-07, Vol.370 (9581), p.49-58</ispartof><rights>Elsevier Ltd</rights><rights>2007 Elsevier Ltd</rights><rights>Copyright Elsevier Limited Jul 7-Jul 13, 2007</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c445t-323e31ec08b4b1c8dad1f3a9b57c175d7323ba3c38b9baa80145c91013f082203</citedby><cites>FETCH-LOGICAL-c445t-323e31ec08b4b1c8dad1f3a9b57c175d7323ba3c38b9baa80145c91013f082203</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktohtml>$$Uhttps://www.sciencedirect.com/science/article/pii/S0140673607610496$$EHTML$$P50$$Gelsevier$$H</linktohtml><link.rule.ids>314,776,780,3537,27901,27902,65306</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/17617272$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Madruga, José Valdez, Dr</creatorcontrib><creatorcontrib>Berger, Daniel, MD</creatorcontrib><creatorcontrib>McMurchie, Marilyn, MD</creatorcontrib><creatorcontrib>Suter, Fredy, MD</creatorcontrib><creatorcontrib>Banhegyi, Denes, MD</creatorcontrib><creatorcontrib>Ruxrungtham, Kiat, MD</creatorcontrib><creatorcontrib>Norris, Dorece, MD</creatorcontrib><creatorcontrib>Lefebvre, Eric, MD</creatorcontrib><creatorcontrib>de Béthune, Marie-Pierre, PhD</creatorcontrib><creatorcontrib>Tomaka, Frank, MD</creatorcontrib><creatorcontrib>De Pauw, Martine, PharmD</creatorcontrib><creatorcontrib>Vangeneugden, Tony, MSc</creatorcontrib><creatorcontrib>Spinosa-Guzman, Sabrina, MD</creatorcontrib><creatorcontrib>on behalf of the TITAN study group</creatorcontrib><creatorcontrib>TITAN study group</creatorcontrib><title>Efficacy and safety of darunavir-ritonavir compared with that of lopinavir-ritonavir at 48 weeks in treatment-experienced, HIV-infected patients in TITAN: a randomised controlled phase III trial</title><title>The Lancet (British edition)</title><addtitle>Lancet</addtitle><description>Summary Background The protease inhibitor darunavir has been shown to be efficacious in highly treatment-experienced patients with HIV infection, but needs to be assessed in patients with a broader range of treatment experience. We did a randomised, controlled, phase III trial (TITAN) to compare 48-week efficacy and safety of darunavir-ritonavir with that of lopinavir-ritonavir in treatment-experienced, lopinavir-naive patients. Methods Patients received optimised background regimen plus non-blinded treatment with darunavir-ritonavir 600/100 mg twice daily or lopinavir-ritonavir 400/100 mg twice daily. The primary endpoint was non-inferiority (95% CI lower limit for the difference in treatment response −12% or greater) for HIV RNA of less than 400 copies per mL in plasma at week 48 (per-protocol analysis). TITAN (TMC114-C214) is registered with ClinicalTrials.gov , number NCT00110877. Findings Of 595 patients randomised and treated, 187 (31%) were protease inhibitor naive; 476 of 582 (82%) were susceptible to four or more protease inhibitors. At week 48, significantly more darunavir-ritonavir than lopinavir-ritonavir patients had HIV RNA of less than 400 copies per mL (77% [220 of 286] vs 68% [199 of 293]; estimated difference 9%, 95% CI 2–16). Fewer virological failures treated with darunavir-ritonavir than with lopinavir-ritonavir developed primary protease inhibitor mutations (21% [n=6] vs 36% [n=20]) and nucleoside analogue-associated mutations (14% [n=4] vs 27% [n=15]). Safety data were generally similar between the groups; grade 3 or 4 adverse events occurred in 80 (27%) darunavir-ritonavir and 89 (30%) lopinavir-ritonavir patients. Interpretation In lopinavir-naive, treatment-experienced patients, darunavir-ritonavir was non-inferior to lopinavir-ritonavir treatment in terms of our virological endpoint, and should therefore be considered as a treatment option for this population.</description><subject>Adult</subject><subject>Antiretroviral drugs</subject><subject>Antiretroviral Therapy, Highly Active</subject><subject>Clinical trials</subject><subject>Darunavir</subject><subject>Drug therapy</subject><subject>Female</subject><subject>HIV</subject><subject>HIV Infections - drug therapy</subject><subject>HIV Protease Inhibitors - adverse effects</subject><subject>HIV Protease Inhibitors - therapeutic use</subject><subject>HIV-1 - drug effects</subject><subject>Human immunodeficiency virus</subject><subject>Humans</subject><subject>Internal Medicine</subject><subject>Kaposis sarcoma</subject><subject>Lopinavir</subject><subject>Male</subject><subject>Middle Aged</subject><subject>Mutation</subject><subject>Patients</subject><subject>Product safety</subject><subject>Proteinase inhibitors</subject><subject>Pyrimidinones - adverse effects</subject><subject>Pyrimidinones - therapeutic use</subject><subject>Ritonavir</subject><subject>Ritonavir - adverse effects</subject><subject>Ritonavir - therapeutic use</subject><subject>RNA, Viral - blood</subject><subject>Safety</subject><subject>Sulfonamides - adverse effects</subject><subject>Sulfonamides - therapeutic 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and safety of darunavir-ritonavir compared with that of lopinavir-ritonavir at 48 weeks in treatment-experienced, HIV-infected patients in TITAN: a randomised controlled phase III trial</title><author>Madruga, José Valdez, Dr ; Berger, Daniel, MD ; McMurchie, Marilyn, MD ; Suter, Fredy, MD ; Banhegyi, Denes, MD ; Ruxrungtham, Kiat, MD ; Norris, Dorece, MD ; Lefebvre, Eric, MD ; de Béthune, Marie-Pierre, PhD ; Tomaka, Frank, MD ; De Pauw, Martine, PharmD ; Vangeneugden, Tony, MSc ; Spinosa-Guzman, Sabrina, MD</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c445t-323e31ec08b4b1c8dad1f3a9b57c175d7323ba3c38b9baa80145c91013f082203</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2007</creationdate><topic>Adult</topic><topic>Antiretroviral drugs</topic><topic>Antiretroviral Therapy, Highly Active</topic><topic>Clinical trials</topic><topic>Darunavir</topic><topic>Drug therapy</topic><topic>Female</topic><topic>HIV</topic><topic>HIV Infections - drug therapy</topic><topic>HIV Protease Inhibitors - adverse effects</topic><topic>HIV Protease Inhibitors - therapeutic use</topic><topic>HIV-1 - drug effects</topic><topic>Human immunodeficiency virus</topic><topic>Humans</topic><topic>Internal Medicine</topic><topic>Kaposis sarcoma</topic><topic>Lopinavir</topic><topic>Male</topic><topic>Middle Aged</topic><topic>Mutation</topic><topic>Patients</topic><topic>Product safety</topic><topic>Proteinase inhibitors</topic><topic>Pyrimidinones - adverse effects</topic><topic>Pyrimidinones - therapeutic use</topic><topic>Ritonavir</topic><topic>Ritonavir - adverse effects</topic><topic>Ritonavir - therapeutic use</topic><topic>RNA, Viral - blood</topic><topic>Safety</topic><topic>Sulfonamides - adverse effects</topic><topic>Sulfonamides - therapeutic use</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Madruga, José 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Central Basic</collection><collection>SIRS Editorial</collection><jtitle>The Lancet (British edition)</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Madruga, José Valdez, Dr</au><au>Berger, Daniel, MD</au><au>McMurchie, Marilyn, MD</au><au>Suter, Fredy, MD</au><au>Banhegyi, Denes, MD</au><au>Ruxrungtham, Kiat, MD</au><au>Norris, Dorece, MD</au><au>Lefebvre, Eric, MD</au><au>de Béthune, Marie-Pierre, PhD</au><au>Tomaka, Frank, MD</au><au>De Pauw, Martine, PharmD</au><au>Vangeneugden, Tony, MSc</au><au>Spinosa-Guzman, Sabrina, MD</au><aucorp>on behalf of the TITAN study group</aucorp><aucorp>TITAN study group</aucorp><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Efficacy and safety of darunavir-ritonavir compared with that of lopinavir-ritonavir at 48 weeks in treatment-experienced, HIV-infected patients in TITAN: a randomised controlled phase III trial</atitle><jtitle>The Lancet (British edition)</jtitle><addtitle>Lancet</addtitle><date>2007-07-07</date><risdate>2007</risdate><volume>370</volume><issue>9581</issue><spage>49</spage><epage>58</epage><pages>49-58</pages><issn>0140-6736</issn><eissn>1474-547X</eissn><coden>LANCAO</coden><abstract>Summary Background The protease inhibitor darunavir has been shown to be efficacious in highly treatment-experienced patients with HIV infection, but needs to be assessed in patients with a broader range of treatment experience. We did a randomised, controlled, phase III trial (TITAN) to compare 48-week efficacy and safety of darunavir-ritonavir with that of lopinavir-ritonavir in treatment-experienced, lopinavir-naive patients. Methods Patients received optimised background regimen plus non-blinded treatment with darunavir-ritonavir 600/100 mg twice daily or lopinavir-ritonavir 400/100 mg twice daily. The primary endpoint was non-inferiority (95% CI lower limit for the difference in treatment response −12% or greater) for HIV RNA of less than 400 copies per mL in plasma at week 48 (per-protocol analysis). TITAN (TMC114-C214) is registered with ClinicalTrials.gov , number NCT00110877. Findings Of 595 patients randomised and treated, 187 (31%) were protease inhibitor naive; 476 of 582 (82%) were susceptible to four or more protease inhibitors. At week 48, significantly more darunavir-ritonavir than lopinavir-ritonavir patients had HIV RNA of less than 400 copies per mL (77% [220 of 286] vs 68% [199 of 293]; estimated difference 9%, 95% CI 2–16). Fewer virological failures treated with darunavir-ritonavir than with lopinavir-ritonavir developed primary protease inhibitor mutations (21% [n=6] vs 36% [n=20]) and nucleoside analogue-associated mutations (14% [n=4] vs 27% [n=15]). Safety data were generally similar between the groups; grade 3 or 4 adverse events occurred in 80 (27%) darunavir-ritonavir and 89 (30%) lopinavir-ritonavir patients. Interpretation In lopinavir-naive, treatment-experienced patients, darunavir-ritonavir was non-inferior to lopinavir-ritonavir treatment in terms of our virological endpoint, and should therefore be considered as a treatment option for this population.</abstract><cop>England</cop><pub>Elsevier Ltd</pub><pmid>17617272</pmid><doi>10.1016/S0140-6736(07)61049-6</doi><tpages>10</tpages></addata></record> |
| fulltext | fulltext |
| identifier | ISSN: 0140-6736 |
| ispartof | The Lancet (British edition), 2007-07, Vol.370 (9581), p.49-58 |
| issn | 0140-6736 1474-547X |
| language | eng |
| recordid | cdi_proquest_journals_198994369 |
| source | MEDLINE; Elsevier ScienceDirect Journals |
| subjects | Adult Antiretroviral drugs Antiretroviral Therapy, Highly Active Clinical trials Darunavir Drug therapy Female HIV HIV Infections - drug therapy HIV Protease Inhibitors - adverse effects HIV Protease Inhibitors - therapeutic use HIV-1 - drug effects Human immunodeficiency virus Humans Internal Medicine Kaposis sarcoma Lopinavir Male Middle Aged Mutation Patients Product safety Proteinase inhibitors Pyrimidinones - adverse effects Pyrimidinones - therapeutic use Ritonavir Ritonavir - adverse effects Ritonavir - therapeutic use RNA, Viral - blood Safety Sulfonamides - adverse effects Sulfonamides - therapeutic use |
| title | Efficacy and safety of darunavir-ritonavir compared with that of lopinavir-ritonavir at 48 weeks in treatment-experienced, HIV-infected patients in TITAN: a randomised controlled phase III trial |
| url | https://sfx.bib-bvb.de/sfx_tum?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&ctx_tim=2025-02-08T11%3A21%3A55IST&url_ver=Z39.88-2004&url_ctx_fmt=infofi/fmt:kev:mtx:ctx&rfr_id=info:sid/primo.exlibrisgroup.com:primo3-Article-proquest_cross&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.atitle=Efficacy%20and%20safety%20of%20darunavir-ritonavir%20compared%20with%20that%20of%20lopinavir-ritonavir%20at%2048%20weeks%20in%20treatment-experienced,%20HIV-infected%20patients%20in%20TITAN:%20a%20randomised%20controlled%20phase%20III%20trial&rft.jtitle=The%20Lancet%20(British%20edition)&rft.au=Madruga,%20Jos%C3%A9%20Valdez,%20Dr&rft.aucorp=on%20behalf%20of%20the%20TITAN%20study%20group&rft.date=2007-07-07&rft.volume=370&rft.issue=9581&rft.spage=49&rft.epage=58&rft.pages=49-58&rft.issn=0140-6736&rft.eissn=1474-547X&rft.coden=LANCAO&rft_id=info:doi/10.1016/S0140-6736(07)61049-6&rft_dat=%3Cproquest_cross%3E1302886581%3C/proquest_cross%3E%3Curl%3E%3C/url%3E&disable_directlink=true&sfx.directlink=off&sfx.report_link=0&rft_id=info:oai/&rft_pqid=198994369&rft_id=info:pmid/17617272&rft_els_id=S0140673607610496&rfr_iscdi=true |