Author | Wallis, Carole L. | |
Author | Hughes, Michael D. | |
Author | Ritz, Justin | |
Author | Viana, Raquel | |
Author | Jesus, Carlos Silva de | |
Author | Saravanan, Shanmugam | |
Author | Schalkwyk, Marije van | |
Author | Mngqibisa, Rosie | |
Author | Salata, Robert | |
Author | Mugyenyi, Peter | |
Author | Hogg, Evelyn | |
Author | Hovind, Laura | |
Author | Wieclaw, Linda | |
Author | Gross, Robert | |
Author | Godfrey, Catherine | |
Author | Collier, Ann C. | |
Author | Grinsztejn, Beatriz | |
Author | Mellors, John W. | |
Access date | 2020-11-27T00:07:48Z | |
Available date | 2020-11-27T00:07:48Z | |
Document date | 2020 | |
Citation | WALLIS, Carole 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, v. 71, n. 7, p. 170-177, 2020. | pt_BR |
ISSN | 1058-4838 | pt_BR |
URI | https://www.arca.fiocruz.br/handle/icict/44658 | |
Language | eng | pt_BR |
Publisher | Oxford | pt_BR |
Rights | restricted access | pt_BR |
Title | Diverse HIV-1 Drug Resistance Profiles at Screening for ACTG A5288: A Study of People Experiencing Virologic Failure on Second-line ART in Resource Limited Settings | pt_BR |
Type | Article | pt_BR |
DOI | 10.1093/cid/ciz1116 | |
Abstract | 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. | pt_BR |
Affilliation | Bio Analytical Research Corporation South Africa and Lancet Laboratories. Johannesburg, South Africa. | pt_BR |
Affilliation | Harvard TH Chan School of Public Health. Boston, Massachusetts, USA. | pt_BR |
Affilliation | Harvard TH Chan School of Public Health. Boston, Massachusetts, USA. | pt_BR |
Affilliation | Bio Analytical Research Corporation South Africa and Lancet Laboratories. Johannesburg, South Africa. | pt_BR |
Affilliation | Fundação Oswaldo Cruz. Instituto Nacional de Infectologia Evandro Chagas. Rio de Janeiro, RJ, Brasil. | pt_BR |
Affilliation | Y.R. Gaitonde Centre for AIDS Research and Education. Chennai, India. | pt_BR |
Affilliation | Stellenbosch University. Family Clinical Research Unit Clinical Research Site. Cape Town, South Africa. | pt_BR |
Affilliation | Enhancing Care Foundation. Durban Adult Human Immunodeficiency Virus Clinical Research Site. Durban, South Africa. | pt_BR |
Affilliation | Case Western Reserve University. Department of Medicine. Cleveland, Ohio, USA. | pt_BR |
Affilliation | Joint Clinical Research Center. Kampala, Uganda. | pt_BR |
Affilliation | Social and Scientific Systems. Silver Spring, Maryland, USA. | pt_BR |
Affilliation | Frontier Science & Technology Research Foundation. Amherst, New York, USA. | pt_BR |
Affilliation | Frontier Science & Technology Research Foundation. Amherst, New York, USA. | pt_BR |
Affilliation | University of Pennsylvania. Philadelphia, Pennsylvania, USA. | pt_BR |
Affilliation | National Institutes of Health. National Institute of Allergy and Infectious Diseases. Division of Acquired Immunodeficiency Syndrome. Bethesda, Maryland, USA. | pt_BR |
Affilliation | University of Washington. School of Medicine. Seattle, Washington, USA. | pt_BR |
Affilliation | Fundação Oswaldo Cruz. Instituto Nacional de Infectologia Evandro Chagas. Laboratório de Pesquisa Clínica em DST/AIDS. Rio de Janeiro, RJ, Brasil. | pt_BR |
Affilliation | University of Pittsburgh. School of Medicine. Department of Medicine. Division of Infectious Diseases. Pittsburgh, Pennsylvania, USA. | pt_BR |
Subject | HIV-1 drug resistance | pt_BR |
Subject | Non-subtype B | pt_BR |
Subject | Resource-limited setting | pt_BR |
Subject | Second-line ART failure | pt_BR |