Inhibition of HTLV-1 Infection by HIV-1 First- and Second-Generation Integrase Strand Transfer Inhibitors

ABSTRACT Second-generation HIV-1 integrase strand transfer inhibitors (INSTIs) dolutegravir (DTG), bictegravir (BIC), and cabotegravir (CAB) showed a high genetic barrier to resistance and limited cross-resistance with first-generation INSTIs raltegravir (RAL) and elvitegravir (EVG). In this study, DTG, BIC, and CAB demonstrated a comparable activity on a panel of INSTI-resistant strains isolated from patients exposed to RAL, EVG, and/or DTG, with a significantly reduced susceptibility only with the pathway Q148H/K/R plus one to two additional INSTI mutations.

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Correction to Discovery of 2-Pyridinone Aminals: A Prodrug Strategy to Advance a Second Generation of HIV-1 Integrase Strand Transfer Inhibitors

Journal of Medicinal Chemistry ◽

10.1021/acs.jmedchem.5b01957 ◽

2015 ◽

Vol 59 (1) ◽

pp. 486-486 ◽

Cited By ~ 1

Author(s):

Izzat T. Raheem ◽

Abbas M. Walji ◽

Daniel Klein ◽

John M. Sanders ◽

David A. Powell ◽

...

Keyword(s):

Second Generation ◽

Strand Transfer ◽

Integrase Strand Transfer Inhibitors ◽

Hiv 1

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Integrase Strand Transfer Inhibitors Are Effective Anti-HIV Drugs

Viruses ◽

10.3390/v13020205 ◽

2021 ◽

Vol 13 (2) ◽

pp. 205

Author(s):

Steven J. Smith ◽

Xue Zhi Zhao ◽

Dario Oliveira Passos ◽

Dmitry Lyumkis ◽

Terrence R. Burke ◽

...

Keyword(s):

First Generation ◽

Second Generation ◽

Treatment Strategies ◽

Strand Transfer ◽

Current State ◽

Integrase Strand Transfer Inhibitors ◽

Hiv Drugs ◽

Exposure Prophylaxis ◽

Emergence Of Resistance ◽

Hiv 1

Integrase strand transfer inhibitors (INSTIs) are currently recommended for the first line treatment of human immunodeficiency virus type one (HIV-1) infection. The first-generation INSTIs are effective but can select for resistant viruses. Recent advances have led to several potent second-generation INSTIs that are effective against both wild-type (WT) HIV-1 integrase and many of the first-generation INSTI-resistant mutants. The emergence of resistance to these new second-generation INSTIs has been minimal, which has resulted in alternative treatment strategies for HIV-1 patients. Moreover, because of their high antiviral potencies and, in some cases, their bioavailability profiles, INSTIs will probably have prominent roles in pre-exposure prophylaxis (PrEP). Herein, we review the current state of the clinically relevant INSTIs and discuss the future outlook for this class of antiretrovirals.

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Impact of HIV-1 Integrase L74F and V75I Mutations in a Clinical Isolate on Resistance to Second-Generation Integrase Strand Transfer Inhibitors

Antimicrobial Agents and Chemotherapy ◽

10.1128/aac.00315-17 ◽

2017 ◽

Vol 61 (8) ◽

Cited By ~ 12

Author(s):

Atsuko Hachiya ◽

Karen A. Kirby ◽

Yoko Ido ◽

Urara Shigemi ◽

Masakazu Matsuda ◽

...

Keyword(s):

Clinical Isolate ◽

Virological Failure ◽

Rational Design ◽

Clinical Case ◽

First Generation ◽

Second Generation ◽

Strand Transfer ◽

Integrase Strand Transfer Inhibitors ◽

Mutation Pattern ◽

Hiv 1

ABSTRACT A novel HIV-1 integrase mutation pattern, L74F V75I, which conferred resistance to first-generation integrase strand transfer inhibitors (INSTIs), was identified in a clinical case with virological failure under a raltegravir-based regimen. Addition of L74F V75I to N155H or G140S Q148H increased resistance levels to the second-generation INSTIs dolutegravir (>385- and 100-fold, respectively) and cabotegravir (153- and 197-fold, respectively). These findings are important for the development of an accurate system for interpretation of INSTI resistance and the rational design of next-generation INSTIs.

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Effects of integrase inhibitor-based antiretroviral therapy on brain outcomes according to time since acquisition of HIV-1 infection

Scientific Reports ◽

10.1038/s41598-021-90678-6 ◽

2021 ◽

Vol 11 (1) ◽

Author(s):

Anna Prats ◽

Ignacio Martínez-Zalacaín ◽

Beatriz Mothe ◽

Eugènia Negredo ◽

Núria Pérez-Álvarez ◽

...

Keyword(s):

Antiretroviral Therapy ◽

Integrase Inhibitor ◽

Strand Transfer ◽

Cognitive Differences ◽

Integrase Strand Transfer Inhibitors ◽

Initiation Of Therapy ◽

Main Component ◽

Living With Hiv ◽

The Impact ◽

Hiv 1

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.

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