In the SAILING study, dolutegravir demonstrated superior virologic efficacy compared with raltegravir in treatment-experienced, integrase strand transfer inhibitor (INSTI)-naive patients with HIV-1 who harbored resistance to ≥2 antiretroviral drug classes. Significantly fewer dolutegravir-treated patients demonstrated virologic failure with treatment-emergent resistance than raltegravir-treated patients through 48 weeks. Investigator-selected background therapy (ISBT) included at least one fully active agent, selected on the basis of resistance analysis. Genotypic and phenotypic resistance testing were performed on baseline and time-of-failure samples from patients with protocol-defined virologic failure (PDVF). A post hoc analysis of SAILING (N = 715; 354 dolutegravir, 361 raltegravir) assessed efficacy in subpopulations defined by ISBT activity, resistance profiles, and treatment history. When ISBT contained only nucleoside reverse transcriptase inhibitors (NRTIs), PDVF occurred in 0% (0/32) of dolutegravir-treated patients and 21.9% (7/32) of raltegravir-treated patients (p = .005). In patients harboring M184 V whose ISBT contained lamivudine or emtricitabine plus a second NRTI, 0% (0/13) of dolutegravir- and 33.3% (4/12) of raltegravir-treated patients (p = .026) experienced PDVF. Among patients receiving protease inhibitor (PI)-containing ISBT, 6.0% (18/300) of dolutegravir-treated patients versus 11.8% (36/305) of raltegravir-treated patients (p = .012) experienced PDVF. Darunavir/ritonavir was part of ISBT in 130 dolutegravir-treated patients and 145 raltegravir-treated patients; 6 (4.6%) and 12 (8.3%), respectively, experienced PDVF (difference -3.7%; 95% confidence interval: -10.1% to 2.5%; p = .256). There was no or less virologic failure in treatment-experienced, INSTI-naive subjects receiving dolutegravir versus raltegravir, even when the ISBT was suboptimal or NRTI resistance was present at baseline. These findings are not explained by the use of PI/ritonavir-containing ISBT.
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http://dx.doi.org/10.1089/AID.2017.0184 | DOI Listing |
Front Microbiol
September 2019
Laboratory for Functional Genomics and Bioinformatics, Instituto Oswaldo Cruz, Oswaldo Cruz Foundation (Fiocruz), Rio de Janeiro, Brazil.
The human immunodeficiency virus type 1 (HIV-1) has several proteins of therapeutic importance, many of which are currently used as drug targets in antiretroviral therapy. Among these proteins is the integrase, which is responsible for the integration of the viral DNA into the host genome - a crucial step for HIV-1 replication. Given the importance of this protein in the replication process, three integrase inhibitors are currently used as an option for antiretroviral therapy: Raltegravir, Elvitegravir, and Dolutegravir.
View Article and Find Full Text PDFJ Antimicrob Chemother
March 2019
Infectious and Tropical Diseases, Martinique University Hospital, Fort-de-France, France.
Objectives: To analyse the frequency and causes of treatment discontinuation in patients who were treated with an integrase strand transfer inhibitor (INSTI), with a focus on neuropsychiatric adverse events (NPAEs).
Methods: Patients in 18 HIV reference centres in France were prospectively included in the Dat'AIDS cohort. Data were collected from all patients starting an INSTI-containing regimen between 1 January 2006 and 31 December 2016.
AIDS Res Hum Retroviruses
April 2018
1 ViiV Healthcare , Research Triangle Park, North Carolina.
In the SAILING study, dolutegravir demonstrated superior virologic efficacy compared with raltegravir in treatment-experienced, integrase strand transfer inhibitor (INSTI)-naive patients with HIV-1 who harbored resistance to ≥2 antiretroviral drug classes. Significantly fewer dolutegravir-treated patients demonstrated virologic failure with treatment-emergent resistance than raltegravir-treated patients through 48 weeks. Investigator-selected background therapy (ISBT) included at least one fully active agent, selected on the basis of resistance analysis.
View Article and Find Full Text PDFCurr HIV Res
April 2019
Microbiology Section of the Department of Experimental, Diagnostic and Specialty Medicine, School of Medicine, University of Bologna, Via Massarenti, 9, Bologna, Italy.
Background: Total HIV-DNA load in peripheral blood cell (PBMCs) reflects the global viral reservoir that seems not to be affected by antiretroviral treatment. However, some studies reported a different permeability of different drugs in cellular compartments.
Objective: To investigate the relation between the amount of total HIV-1 DNA and different treatment strategies.
J Glob Antimicrob Resist
December 2015
Department of Molecular Medicine, Sapienza University, Viale di Porta Tiburtina 28, 00185 Rome, Italy. Electronic address:
Recent studies support the idea that human immunodeficiency virus type 1 (HIV-1) drug resistance is declining in developed countries. To help assess the current situation in Italy, the dynamics of drug resistance mutations in pol and integrase genes in plasma samples from HIV-1-positive patients attending Sapienza University Hospital, Rome, from 2003 to 2014 were analysed. In total, 1730 genotype resistance tests (GRTs) were retrospectively analysed.
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