Objectives: We investigated the in vitro phenotypic susceptibility of HIV-2 isolates from integrase inhibitor (INI)-naive patients to INIs and its relation to HIV-2 integrase gene polymorphism.
Methods: We determined the phenotypic susceptibility to raltegravir and elvitegravir of co-cultured isolates obtained from the HIV-2 ROD reference strain and from 14 clinical isolates. IC(50) values were compared with those for HIV-1 reference strains. HIV-2 integrase gene polymorphism was assessed in isolates from 52 INI-naive patients enrolled in the French HIV-2 cohort.
Results: Median raltegravir and elvitegravir IC(50) values for the 14 clinical HIV-2 isolates were 2.4 and 0.7 nM, respectively, and were similar to those observed for HIV-2 ROD and HIV-1 reference strains. Overall, 38% of HIV-2 integrase amino acids were polymorphic. The catalytic triad DDE and the HHCC and RKK motifs were fully conserved, at the same genomic positions as described in HIV-1. In subtype B isolates, the total length of the integrase gene varied, owing to the presence of stop codons at positions 288, 294, 297 and 302. Fourteen of the positions associated with substitutions conferring INI resistance in HIV-1 were polymorphic in HIV-2.
Conclusions: Despite 40% heterogeneity between the HIV-1 and HIV-2 integrase genes, the phenotypic susceptibility of clinical HIV-2 isolates to INIs was similar to that of HIV-1. This new class of antiretroviral drugs thus represents a novel therapeutic possibility for HIV-2-infected patients who otherwise have few treatment options.
Download full-text PDF |
Source |
|---|---|
| http://dx.doi.org/10.1093/jac/dkn335 | DOI Listing |
Publication Analysis
Top Keywords
Similar Publications
Novel Dolutegravir and Lenacapavir Resistance Patterns in Human Immunodeficiency Virus Type 2 Infection: A Case Report.
Open Forum Infect Dis
January 2025
Viroscience Department, Erasmus MC, Rotterdam, The Netherlands.
Background: The treatment management of human immunodeficiency virus (HIV)-2 infection presents greater challenges compared to HIV-1 infection, primarily because of inherent resistance against non-nucleoside reverse transcriptase inhibitors. Integrase strand transfer inhibitors, particularly dolutegravir, have improved treatment outcomes for people with HIV-2. Lenacapavir, a novel and potent antiretroviral capsid inhibitor, offers additional therapeutic options.
View Article and Find Full Text PDFReplicative co-infections with human immunodeficiency virus 1 and 2 as well as hepatitis B and C virus in Ghanaian individuals.
Eur J Microbiol Immunol (Bp)
December 2024
9Department of Tropical Medicine, Bernhard Nocht Institute for Tropical Medicine & I. Department of Medicine, University Medical Center, Hamburg, Germany.
Background: The study assessed replicative human immunodeficiency virus-(HIV-) infection and replicative co-infections as well as molecular determinants of reduced susceptibility towards anti-retroviral therapy in a Ghanaian population of known HIV patients and a control group.
Methods: Real-time PCRs for HIV-1, HIV-2, hepatitis B virus (HBV) and hepatitis C virus (HCV) were run with serum samples from known Ghanaian HIV-patients (n = 975) and control individuals (n = 105). For 108 individuals, HIV-sequence analysis was performed.
Efficacy of Integrase Strand Transfer Inhibitors and the Capsid Inhibitor Lenacapavir against HIV-2, and Exploring the Effect of Raltegravir on the Activity of SARS-CoV-2.
Viruses
October 2024
Laboratory of Retroviral Biochemistry, Department of Biochemistry and Molecular Biology, Faculty of Medicine, University of Debrecen, 4032 Debrecen, Hungary.
Retroviruses perpetuate their survival by incorporating a copy of their genome into the host cell, a critical step catalyzed by the virally encoded integrase. The viral capsid plays an important role during the viral life cycle, including nuclear importation in the case of lentiviruses and integration targeting events; hence, targeting the integrase and the viral capsid is a favorable therapeutic strategy. While integrase strand transfer inhibitors (INSTIs) are recommended as first-line regimens given their high efficacy and tolerability, lenacapavir is the first capsid inhibitor and the newest addition to the HIV treatment arsenal.
View Article and Find Full Text PDFA cGAS-mediated type I interferon response in human CD4+ T cells depends on productive infection and is conserved over HIV types and strains.
J Virol
October 2024
Department of Diagnostic Sciences, Ghent University, Ghent, Belgium.
Human immunodeficiency virus (HIV) type 2 is known to be less pathogenic than HIV-1, possibly due to more effective immune control mechanisms. The mechanism of innate sensing of HIV-2 by T cells is at present unclear. In this study, we show that several primary isolates of HIV-2 (CBL20 and CI85) and HIV-1 (A8 and D2), similar to the molecular clone HIV-1 NL4.
View Article and Find Full Text PDFComprehensive database of HIV mutations selected during antiretroviral in vitro passage experiments.
Antiviral Res
October 2024
Division of Infectious Diseases, Department of Medicine, Stanford University, Stanford, CA, 94305, USA. Electronic address:
Background: In vitro passage experiments are crucial to the development of antiretroviral (ARV) drugs.
Methods: We created an online database containing data from 102 published studies in which HIV-1 or HIV-2 was cultured with increasing concentrations of the FDA-approved nucleoside RT inhibitors (NRTIs), nonnucleoside RT inhibitors (NNRTIs), integrase strand transfer inhibitors (INSTIs), protease inhibitors (PIs), capsid inhibitor (CAI) lenacapavir, and nucleoside RT translocation inhibitor (NRTTI) islatravir. We summarized the mutations selected in the subset of passage experiments with NRTIs lamivudine (3TC), emtricitabine (FTC), abacavir (ABC), tenofovir (TFV), and zidovudine (AZT), NNRTIs doravirine (DOR), efavirenz (EFV), and rilpivirine (RPV), INSTIs bictegravir (BIC), cabotegravir (CAB), and dolutegravir (DTG), and PIs atazanavir (ATV), darunavir (DRV), and lopinavir (LPV).
Want AI Summaries of new PubMed Abstracts delivered to your In-box?
Enter search terms and have AI summaries delivered each week - change queries or unsubscribe any time!