Abstract:
INTRODUCTION:Dolutegravir is a second generation integrase inhibitor with a proposed high genetic barrier to resistance. However, in clinical trials, decreased virological response was seen in a subset of patients with prior exposure to raltegravir and multiple integrase resistance mutations. METHODS:We describe two cases of HIV subtype B-infected patients starting dolutegravir after previous failure on a raltegravir-containing regimen with extensive resistance. Genotypic analysis was performed using population sequencing and 454 ultradeep sequencing of integrase at time of raltegravir exposure. RESULTS:Both patients were diagnosed in early 1990s and received mono- and dual therapy, followed by several cART-regimens. Due to presence of extensive resistance, the genotypic susceptibility score of these regimens never reached a score >2 and never resulted in sustained virological suppression despite good adherence. Early 2012, the clinical condition of patient 1 worsened during persistent failure of a mega-cART regimen despite excellent drug levels. Six major PI, six minor PI, seven NRTI, six NNRTI and two INI mutations plus DM-virus were detected (Table 1). Ultra-deep sequencing of integrase showed the selection of Q148R, E138K+Q148K, and N155H variants and phenotypic raltegravir resistance was demonstrated. After addition of dolutegravir and enfuvirtide to the failing regimen (zidovudine, lamivudine, tenofovir, etravirine, darunavir/ritonavir, maraviroc), viral load (VL) decreased from 244,000 to <20 cps/mL within five months, CD4-count increased (33 to 272 mm(3)) and the clinical condition improved substantially. In patient 2, similar worsening of the clinical condition was observed late 2012 during persistent failure on mega-cART. Five major PI, six minor PI, nine NRTI, seven NNRTI and one INI mutation plus DM-virus were detected. Ultra-deep sequencing showed selection of N155H, followed by Q95K and V151I variants and phenotypic raltegravir resistance was demonstrated. Dolutegravir was added to his failing regimen (zidovudine, lamivudine, etravirine, atazanavir/ritonavir, maraviroc) at a VL of 39,000 cps/mL. Sustained virological suppression was reached within five months with considerable increase of CD4-count (41 to 175 mm(3)) and slight improvement of clinical condition. CONCLUSIONS:We present the first patients with extensive integrase resistance who were treated with dolutegravir in clinical practice and who achieved excellent virological and immunological success. These cases demonstrate the high genetic barrier of dolutegravir.
journal_name
J Int AIDS Socjournal_title
Journal of the International AIDS Societyauthors
Hofstra LM,Nijhuis M,Mudrikova T,Fun A,Schipper P,Schneider M,Wensing Adoi
10.7448/IAS.17.4.19755subject
Has Abstractpub_date
2014-11-02 00:00:00pages
19755issue
4 Suppl 3issn
1758-2652pii
19755journal_volume
17pub_type
杂志文章abstract:INTRODUCTION:HIV self-testing (HIVST) offers an alternative to facility-based HIV testing services, particularly for populations such as men who have sex with men (MSM) who may fear accessing testing due to stigma, discrimination and criminalization. Innovative HIV testing approaches are needed to meet the goal of 90% ...
journal_title:Journal of the International AIDS Society
pub_type: 杂志文章
doi:10.1002/jia2.25124
更新日期:2018-07-01 00:00:00
abstract:INTRODUCTION:Routes of transmission and reasons for HIV testing are important epidemiologic data to analyze the epidemic and to tailor the response to AIDS. The aim of this study was to analyze reasons for testing and transmission ways of HIV among recently diagnosed HIV patients registered in the multicenter HIV-TR co...
journal_title:Journal of the International AIDS Society
pub_type: 杂志文章
doi:10.7448/IAS.17.4.19595
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abstract:INTRODUCTION:A key objective of combined antiretroviral therapy (cART) is to reach and maintain high CD4 cell counts to provide long-term protection against AIDS-defining opportunistic infections and malignancies, as well as other comorbidities. However, a high proportion of patients present late for care. Our objectiv...
journal_title:Journal of the International AIDS Society
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journal_title:Journal of the International AIDS Society
pub_type: 杂志文章
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更新日期:2019-04-01 00:00:00
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journal_title:Journal of the International AIDS Society
pub_type: 杂志文章,评审
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更新日期:2012-07-05 00:00:00
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journal_title:Journal of the International AIDS Society
pub_type: 杂志文章,评审
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journal_title:Journal of the International AIDS Society
pub_type: 杂志文章,随机对照试验
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journal_title:Journal of the International AIDS Society
pub_type: 杂志文章
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journal_title:Journal of the International AIDS Society
pub_type: 杂志文章
doi:10.7448/IAS.18.1.19247
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journal_title:Journal of the International AIDS Society
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journal_title:Journal of the International AIDS Society
pub_type: 杂志文章
doi:10.7448/IAS.19.1.20627
更新日期:2016-02-23 00:00:00
abstract:BACKGROUND:Micronutrient deficiencies compromise the survival of HIV-infected children in low-income countries. We assessed the effect of multiple micronutrient supplementation on the mortality of HIV-infected children in Uganda. METHODS:In a randomized, controlled trial, 847 children aged one to five years and attend...
journal_title:Journal of the International AIDS Society
pub_type: 杂志文章,随机对照试验
doi:10.1186/1758-2652-13-18
更新日期:2010-06-03 00:00:00
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journal_title:Journal of the International AIDS Society
pub_type: 杂志文章
doi:10.7448/IAS.19.1.20772
更新日期:2016-06-07 00:00:00
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journal_title:Journal of the International AIDS Society
pub_type: 杂志文章
doi:10.7448/IAS.20.1.21467
更新日期:2017-03-08 00:00:00
abstract:BACKGROUND:This retrospective survey describes types of cancers diagnosed in HIV-infected subjects in Asia, and assesses risk factors for cancer in HIV-infected subjects using contemporaneous HIV-infected controls without cancer. METHODS:TREAT Asia HIV Observational Database (TAHOD) sites retrospectively reviewed clin...
journal_title:Journal of the International AIDS Society
pub_type: 杂志文章
doi:10.1186/1758-2652-13-51
更新日期:2010-12-10 00:00:00
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journal_title:Journal of the International AIDS Society
pub_type: 杂志文章,随机对照试验
doi:10.1002/jia2.25247
更新日期:2019-03-01 00:00:00
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journal_title:Journal of the International AIDS Society
pub_type: 杂志文章
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更新日期:2018-03-01 00:00:00
abstract:INTRODUCTION:Guidelines regarding antiretroviral therapy (ART) initiation in HIV infection have varied over time, with the 2015 World Health Organization recommendation suggesting ART initiation at the time of diagnosis regardless of CD4 T-cell counts. Herein, we investigated the influence of socio-demographic and clin...
journal_title:Journal of the International AIDS Society
pub_type: 杂志文章
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更新日期:2018-02-01 00:00:00
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journal_title:Journal of the International AIDS Society
pub_type: 杂志文章,随机对照试验
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journal_title:Journal of the International AIDS Society
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journal_title:Journal of the International AIDS Society
pub_type: 杂志文章
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journal_title:Journal of the International AIDS Society
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journal_title:Journal of the International AIDS Society
pub_type: 杂志文章,评审
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journal_title:Journal of the International AIDS Society
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更新日期:2020-08-01 00:00:00
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journal_title:Journal of the International AIDS Society
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pub_type: 杂志文章,随机对照试验
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abstract::[This corrects the article DOI: 10.7448/IAS.20.01/21317.]. ...
journal_title:Journal of the International AIDS Society
pub_type: 已发布勘误
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更新日期:2017-06-02 00:00:00
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