Carole L Wallis, Michael D Hughes, Justin Ritz, Raquel Viana, Carlos Silva de Jesus, Shanmugam Saravanan, Marije van Schalkwyk, Rosie Mngqibisa, Robert Salata, Peter Mugyenyi, Evelyn Hogg, Laura Hovind, Linda Wieclaw, Robert Gross, Catherine Godfrey, Ann C Collier, Beatriz Grinsztejn, John W Mellors
{"title":"筛选ACTG A5288的不同HIV-1耐药谱:在资源有限的情况下，二线抗逆转录病毒治疗出现病毒学失败的人的研究","authors":"Carole L Wallis, Michael D Hughes, Justin Ritz, Raquel Viana, Carlos Silva de Jesus, Shanmugam Saravanan, Marije van Schalkwyk, Rosie Mngqibisa, Robert Salata, Peter Mugyenyi, Evelyn Hogg, Laura Hovind, Linda Wieclaw, Robert Gross, Catherine Godfrey, Ann C Collier, Beatriz Grinsztejn, John W Mellors","doi":"10.1093/cid/ciz1116","DOIUrl":null,"url":null,"abstract":"<p><strong>Background: </strong>Human immunodeficiency virus (HIV) drug resistance profiles are needed to optimize individual patient management and to develop treatment guidelines. Resistance profiles are not well defined among individuals on failing second-line antiretroviral therapy (ART) in low- and middle-income countries (LMIC).</p><p><strong>Methods: </strong>Resistance genotypes were performed during screening for enrollment into a trial of third-line ART (AIDS Clinical Trials Group protocol 5288). Prior exposure to both nucleoside reverse transcriptase inhibitors (NRTIs) and non-NRTIs and confirmed virologic failure on a protease inhibitor-containing regimen were required. Associations of drug resistance with sex, age, treatment history, plasma HIV RNA, nadir CD4+T-cell count, HIV subtype, and country were investigated.</p><p><strong>Results: </strong>Plasma HIV genotypes were analyzed for 653 screened candidates; most had resistance (508 of 653; 78%) to 1 or more drugs. Genotypes from 133 (20%) showed resistance to at least 1 drug in a drug class, from 206 (32%) showed resistance to at least 1 drug in 2 drug classes, and from 169 (26%) showed resistance to at least 1 drug in all 3 commonly available drug classes. Susceptibility to at least 1 second-line regimen was preserved in 59%, as were susceptibility to etravirine (78%) and darunavir/ritonavir (97%). Susceptibility to a second-line regimen was significantly higher among women, younger individuals, those with higher nadir CD4+ T-cell counts, and those who had received lopinavir/ritonavir, but was lower among prior nevirapine recipients.</p><p><strong>Conclusions: </strong>Highly divergent HIV drug resistance profiles were observed among candidates screened for third-line ART in LMIC, ranging from no resistance to resistance to 3 drug classes. These findings underscore the need for access to resistance testing and newer antiretrovirals for the optimal management of third-line ART in LMIC.</p>","PeriodicalId":10421,"journal":{"name":"Clinical Infectious Diseases: An Official Publication of the Infectious Diseases Society of America","volume":"14 1","pages":"e170-e177"},"PeriodicalIF":0.0000,"publicationDate":"2020-10-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7583422/pdf/","citationCount":"0","resultStr":"{\"title\":\"Diverse Human Immunodeficiency Virus-1 Drug Resistance Profiles at Screening for ACTG A5288: A Study of People Experiencing Virologic Failure on Second-line Antiretroviral Therapy in Resource-limited Settings.\",\"authors\":\"Carole L Wallis, Michael D Hughes, Justin Ritz, Raquel Viana, Carlos Silva de Jesus, Shanmugam Saravanan, Marije van Schalkwyk, Rosie Mngqibisa, Robert Salata, Peter Mugyenyi, Evelyn Hogg, Laura Hovind, Linda Wieclaw, Robert Gross, Catherine Godfrey, Ann C Collier, Beatriz Grinsztejn, John W Mellors\",\"doi\":\"10.1093/cid/ciz1116\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<p><strong>Background: </strong>Human immunodeficiency virus (HIV) drug resistance profiles are needed to optimize individual patient management and to develop treatment guidelines. Resistance profiles are not well defined among individuals on failing second-line antiretroviral therapy (ART) in low- and middle-income countries (LMIC).</p><p><strong>Methods: </strong>Resistance genotypes were performed during screening for enrollment into a trial of third-line ART (AIDS Clinical Trials Group protocol 5288). Prior exposure to both nucleoside reverse transcriptase inhibitors (NRTIs) and non-NRTIs and confirmed virologic failure on a protease inhibitor-containing regimen were required. Associations of drug resistance with sex, age, treatment history, plasma HIV RNA, nadir CD4+T-cell count, HIV subtype, and country were investigated.</p><p><strong>Results: </strong>Plasma HIV genotypes were analyzed for 653 screened candidates; most had resistance (508 of 653; 78%) to 1 or more drugs. Genotypes from 133 (20%) showed resistance to at least 1 drug in a drug class, from 206 (32%) showed resistance to at least 1 drug in 2 drug classes, and from 169 (26%) showed resistance to at least 1 drug in all 3 commonly available drug classes. Susceptibility to at least 1 second-line regimen was preserved in 59%, as were susceptibility to etravirine (78%) and darunavir/ritonavir (97%). Susceptibility to a second-line regimen was significantly higher among women, younger individuals, those with higher nadir CD4+ T-cell counts, and those who had received lopinavir/ritonavir, but was lower among prior nevirapine recipients.</p><p><strong>Conclusions: </strong>Highly divergent HIV drug resistance profiles were observed among candidates screened for third-line ART in LMIC, ranging from no resistance to resistance to 3 drug classes. These findings underscore the need for access to resistance testing and newer antiretrovirals for the optimal management of third-line ART in LMIC.</p>\",\"PeriodicalId\":10421,\"journal\":{\"name\":\"Clinical Infectious Diseases: An Official Publication of the Infectious Diseases Society of America\",\"volume\":\"14 1\",\"pages\":\"e170-e177\"},\"PeriodicalIF\":0.0000,\"publicationDate\":\"2020-10-23\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7583422/pdf/\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"Clinical Infectious Diseases: An Official Publication of the Infectious Diseases Society of America\",\"FirstCategoryId\":\"1085\",\"ListUrlMain\":\"https://doi.org/10.1093/cid/ciz1116\",\"RegionNum\":0,\"RegionCategory\":null,\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"\",\"PubModel\":\"\",\"JCR\":\"\",\"JCRName\":\"\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"Clinical Infectious Diseases: An Official Publication of the Infectious Diseases Society of America","FirstCategoryId":"1085","ListUrlMain":"https://doi.org/10.1093/cid/ciz1116","RegionNum":0,"RegionCategory":null,"ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"","JCRName":"","Score":null,"Total":0}
Diverse Human Immunodeficiency Virus-1 Drug Resistance Profiles at Screening for ACTG A5288: A Study of People Experiencing Virologic Failure on Second-line Antiretroviral Therapy in Resource-limited Settings.
Background: Human immunodeficiency virus (HIV) drug resistance profiles are needed to optimize individual patient management and to develop treatment guidelines. Resistance profiles are not well defined among individuals on failing second-line antiretroviral therapy (ART) in low- and middle-income countries (LMIC).
Methods: Resistance genotypes were performed during screening for enrollment into a trial of third-line ART (AIDS Clinical Trials Group protocol 5288). Prior exposure to both nucleoside reverse transcriptase inhibitors (NRTIs) and non-NRTIs and confirmed virologic failure on a protease inhibitor-containing regimen were required. Associations of drug resistance with sex, age, treatment history, plasma HIV RNA, nadir CD4+T-cell count, HIV subtype, and country were investigated.
Results: Plasma HIV genotypes were analyzed for 653 screened candidates; most had resistance (508 of 653; 78%) to 1 or more drugs. Genotypes from 133 (20%) showed resistance to at least 1 drug in a drug class, from 206 (32%) showed resistance to at least 1 drug in 2 drug classes, and from 169 (26%) showed resistance to at least 1 drug in all 3 commonly available drug classes. Susceptibility to at least 1 second-line regimen was preserved in 59%, as were susceptibility to etravirine (78%) and darunavir/ritonavir (97%). Susceptibility to a second-line regimen was significantly higher among women, younger individuals, those with higher nadir CD4+ T-cell counts, and those who had received lopinavir/ritonavir, but was lower among prior nevirapine recipients.
Conclusions: Highly divergent HIV drug resistance profiles were observed among candidates screened for third-line ART in LMIC, ranging from no resistance to resistance to 3 drug classes. These findings underscore the need for access to resistance testing and newer antiretrovirals for the optimal management of third-line ART in LMIC.
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