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

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dc.contributor.authorWallis, Carole L.en_ZA
dc.contributor.authorHughes, Michael D.en_ZA
dc.contributor.authorRitz, Justinen_ZA
dc.contributor.authorViana, Raquelen_ZA
dc.contributor.authorde Jesus, Carlos Silvaen_ZA
dc.contributor.authorSaravanan, Shanmugamen_ZA
dc.contributor.authorvan Schalkwyk, Marijeen_ZA
dc.contributor.authorMngqibisa, Rosieen_ZA
dc.contributor.authorSalata, Roberten_ZA
dc.contributor.authorMugyenyi, Peteren_ZA
dc.contributor.authorHogg, Evelynen_ZA
dc.contributor.authorHovind, Lauraen_ZA
dc.contributor.authorWieclaw, Lindaen_ZA
dc.contributor.authorGross, Roberten_ZA
dc.contributor.authorGodfrey, Catherineen_ZA
dc.contributor.authorCollier, Ann C.en_ZA
dc.contributor.authorGrinsztejn, Beatrizen_ZA
dc.contributor.authorMellors, John W.en_ZA
dc.date.accessioned2022-06-02T11:46:17Zen_ZA
dc.date.available2022-06-02T11:46:17Zen_ZA
dc.date.issued2020-10en_ZA
dc.descriptionCITATION: Wallis, C. L. et al. 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. Clinical Infectious Diseases, 71(7): e170–e177. doi:10.1093/cid/ciz1116en_ZA
dc.descriptionThe original publication is available at https://academic.oup.com/cid/en_ZA
dc.description.abstractBackground: 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.en_ZA
dc.description.urihttps://academic.oup.com/cid/article/71/7/e170/5625392?login=trueen_ZA
dc.description.versionPublishers versionen_ZA
dc.format.extent8 pagesen_ZA
dc.identifier.citationWallis, C. L. et al. 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. Clinical Infectious Diseases, 71(7): e170–e177. doi:10.1093/cid/ciz1116en_ZA
dc.identifier.issn1537-6591 (online)en_ZA
dc.identifier.issn1058-4838 (print)en_ZA
dc.identifier.otherdoi:10.1093/cid/ciz1116en_ZA
dc.identifier.urihttp://hdl.handle.net/10019.1/125302en_ZA
dc.language.isoen_ZAen_ZA
dc.publisherOxford University Pressen_ZA
dc.rights.holderAuthors retain copyrighten_ZA
dc.subjectHIV (Viruses)en_ZA
dc.subjectAntiretroviral agentsen_ZA
dc.subjectDrug resistanceen_ZA
dc.titleDiverse 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 Settingsen_ZA
dc.typeArticleen_ZA
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