Susceptibility to HIV-1 integrase strand transfer inhibitors (INSTIs) in highly treatment-experienced patients who failed an INSTI-based regimen

2020 ◽  
Vol 56 (1) ◽  
pp. 106027
Author(s):  
Maria M. Santoro ◽  
Chiara Fornabaio ◽  
Marina Malena ◽  
Laura Galli ◽  
Andrea Poli ◽  
...  
2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Anna Prats ◽  
Ignacio Martínez-Zalacaín ◽  
Beatriz Mothe ◽  
Eugènia Negredo ◽  
Núria Pérez-Álvarez ◽  
...  

AbstractIntegrase strand transfer inhibitors (INSTI) are a main component of the current antiretroviral regimens recommended for treatment of HIV infection. However, little is known about the impact of INSTI on neurocognition and neuroimaging. We developed a prospective observational trial to evaluate the effects of INSTI-based antiretroviral therapy on comprehensive brain outcomes (cognitive, functional, and imaging) according to the time since HIV-1 acquisition. We recruited men living with HIV who initiated antiretroviral therapy with INSTI < 3 months since the estimated date of HIV-1 acquisition (n = 12) and > 6 months since estimated date of HIV-1 acquisition (n = 15). We also recruited a group of matched seronegative individuals (n = 15). Assessments were performed at baseline (before initiation of therapy in HIV arms) and at weeks 4 and 48. Baseline cognitive functioning was comparable between the arms. At week 48, we did not find cognitive differences between starting therapy with INSTI earlier than 3 months or later than 6 months after acquisition of HIV-1 infection. Functional status was poorer in individuals diagnosed earlier. This effect recovered 48 weeks after initiation of therapy. Regarding brain imaging, we found that men living with HIV initiating antiretroviral therapy later experienced a greater decrease in medial orbitofrontal cortex over time, with expected negative repercussions for decision-making tasks.


2016 ◽  
Vol 17 (3) ◽  
pp. 109-113 ◽  
Author(s):  
M. Sayan ◽  
A. Gündüz ◽  
G. Ersöz ◽  
A. İnan ◽  
A. Deveci ◽  
...  

2020 ◽  
Vol 30 (3) ◽  
pp. 126784 ◽  
Author(s):  
Kevin M. Peese ◽  
B. Narasimhulu Naidu ◽  
Manoj Patel ◽  
Chen Li ◽  
David R. Langley ◽  
...  

2020 ◽  
Vol 75 (12) ◽  
pp. 3517-3524
Author(s):  
M Casadellà ◽  
J R Santos ◽  
M Noguera-Julian ◽  
R Micán-Rivera ◽  
P Domingo ◽  
...  

Abstract Background Transmission of resistance mutations to integrase strand transfer inhibitors (INSTIs) in HIV-infected patients may compromise the efficacy of first-line antiretroviral regimens currently recommended worldwide. Continued surveillance of transmitted drug resistance (TDR) is thus warranted. Objectives We evaluated the rates and effects on virological outcomes of TDR in a 96 week prospective multicentre cohort study of ART-naive HIV-1-infected subjects initiating INSTI-based ART in Spain between April 2015 and December 2016. Methods Pre-ART plasma samples were genotyped for integrase, protease and reverse transcriptase resistance using Sanger population sequencing or MiSeq™ using a ≥ 20% mutant sensitivity cut-off. Those present at 1%–19% of the virus population were considered to be low-frequency variants. Results From a total of 214 available samples, 173 (80.8%), 210 (98.1%) and 214 (100.0%) were successfully amplified for integrase, reverse transcriptase and protease genes, respectively. Using a Sanger-like cut-off, the overall prevalence of any TDR, INSTI-, NRTI-, NNRTI- and protease inhibitor (PI)-associated mutations was 13.1%, 1.7%, 3.8%, 7.1% and 0.9%, respectively. Only three (1.7%) subjects had INSTI TDR (R263K, E138K and G163R), while minority variants with integrase TDR were detected in 9.6% of subjects. There were no virological failures during 96 weeks of follow-up in subjects harbouring TDR as majority variants. Conclusions Transmitted INSTI resistance remains rare in Spain and, to date, is not associated with virological failure to first-line INSTI-based regimens.


2013 ◽  
Vol 118 ◽  
pp. 74-82 ◽  
Author(s):  
Mauro Carcelli ◽  
Alessia Bacchi ◽  
Paolo Pelagatti ◽  
Gabriele Rispoli ◽  
Dominga Rogolino ◽  
...  

2015 ◽  
Vol 58 (20) ◽  
pp. 8154-8165 ◽  
Author(s):  
Izzat T. Raheem ◽  
Abbas M. Walji ◽  
Daniel Klein ◽  
John M. Sanders ◽  
David A. Powell ◽  
...  

2016 ◽  
Vol 1 (1) ◽  
pp. 41 ◽  
Author(s):  
Said A. Hassounah ◽  
Thibault Mesplède ◽  
Mark A. Wainberg

Since the discovery of the first inhibitors of HIV replication, drug resistance has been a major problem in HIV therapy, due, in part, to the high mutation rate of HIV. Therefore, the development of a predictive animal model is important to identify impending resistance mutations and to possibly inform treatment decisions. Significant advances have been made possible through use of nonhuman primates infected by SIV, SHIV, and stHIV-1, and use of humanized mouse models of HIV-1 infections. In this review, we describe some of the findings from animal models used for the preclinical testing of integrase strand transfer inhibitors as well as other antiretroviral drugs. These models have led to important findings about the potential role of integrase strand transfer inhibitors in both the prevention and treatment of HIV-1 infection.


Sign in / Sign up

Export Citation Format

Share Document