Prevalence of people living with multidrug‐resistant HIV and limited treatment options in Spain DOI
Josep M. Llibre, Féderico García, José Luís Blanco

et al.

HIV Medicine, Journal Year: 2024, Volume and Issue: 25(8), P. 946 - 957

Published: April 30, 2024

Abstract Objectives Our aim was to determine the prevalence and characteristics of people with HIV on antiretroviral therapy (ART) multidrug resistance (MDR; confirmed three or more [or two plus contraindication one more] core ART classes) limited treatment options (LTOs) in Spain. Methods This an observational, retrospective, multicentre, cross‐sectional chart review study undertaken five reference Spanish centres. Participants were MDR LTOs (detectable viral load [HIV‐RNA >200 copies/mL], treatment‐limiting drug–drug interaction [DDI], intolerance precluding use classes). Prevalence, demographic/clinical characteristics, assessed. Logistic regression analyses used identify MDR‐associated variables. Results Of 14 955 screened HIV, 69 (0.46%) presented 23 (0.15%) had LTOs. The population analysed 73.9% male a median age 54.0 years; time since diagnosis 26.5 years, CD4+ cell count 511.0 cells/μL. only factor significantly associated (univariate analysis) count. Injection drug most common transmission route. Comorbidities (mainly endocrine cardiovascular disorders; 34.8% affecting management) concomitant treatments frequent. No recent opportunistic infections reported. Patients been exposed following ART: nucleoside analogue reverse transcriptase inhibitors (100%), protease (95.6%), non‐nucleoside (87.0%), integrase strand transfer (82.6%). available fully active drugs dolutegravir (39.1%), bictegravir (30.4%), raltegravir (21.7%). Conclusions Spain is very low, approximately half those studied not exhibiting virological suppression. Low counts MDR. These findings may help address impact needs these patients prevent clinical progression HIV.

Language: Английский

New insights into protein–protein interaction modulators in drug discovery and therapeutic advance DOI Creative Commons
Hossam Nada, Yongseok Choi, Sung-Do Kim

et al.

Signal Transduction and Targeted Therapy, Journal Year: 2024, Volume and Issue: 9(1)

Published: Dec. 5, 2024

Abstract Protein-protein interactions (PPIs) are fundamental to cellular signaling and transduction which marks them as attractive therapeutic drug development targets. What were once considered be undruggable targets have become increasingly feasible due the progress that has been made over last two decades rapid technological advances. This work explores influence of innovations on PPI research development. Additionally, diverse strategies for discovering, modulating, characterizing PPIs their corresponding modulators examined with aim presenting a streamlined pipeline advancing PPI-targeted therapeutics. By showcasing carefully selected case studies in modulator discovery development, we illustrate efficacy various identifying, optimizing, overcoming challenges associated design. The valuable lessons insights gained from identification, optimization, approval discussed demonstrating transitioned beyond early-stage now represent prime opportunity significant potential. examples encompass those developed cancer, inflammation immunomodulation, well antiviral applications. perspective aims establish foundation effective targeting modulation using pave way future

Language: Английский

Citations

11
Investigation of Natural Resistance to Fostemsavir and Lenacapavir in Naïve Primary Infections by Ultra-Deep Sequencing of near Full-Length HIV-1 Genomes DOI Creative Commons
Elisabetta Lazzari, Gabriella Rozera, Roberta Gagliardini

et al.

Viruses, Journal Year: 2025, Volume and Issue: 17(5), P. 636 - 636

Published: April 28, 2025

Next-generation sequencing (NGS) of near full-length HIV genomes was performed to investigate natural resistance Fostemsavir (FTR) and Lenacapavir (LEN) at the quasispecies level in nine naïve primary infections harboring different subtypes recombinant forms. Reconstructed provided a median (IQR) coverage for gag env 1710 (750–6063) 1768 (871–5270), respectively. In gp120 encoding region, M426R variant found with frequency 100% two B: one these also showed A204T 100%. more conserved capsid coding region no mutations possibly related LEN were observed.

Language: Английский

Citations

0
In Vitro Anti-HIV-1 Activity of Fucoidans from Brown Algae DOI Creative Commons
Marina Nosik, Krylova Nv, Roza V. Usoltseva

et al.

Marine Drugs, Journal Year: 2024, Volume and Issue: 22(8), P. 355 - 355

Published: July 31, 2024

Due to the developing resistance and intolerance antiretroviral drugs, there is an urgent demand for alternative agents that can suppress viral load in people living with human immunodeficiency virus (HIV). Recently, has been increased interest of marine origin such as, particular, fucoidans HIV replication. In present study, anti-HIV-1 activity from brown algae Alaria marginata, ochotensis, Laminaria longipes, Saccharina cichorioides, gurianovae, Tauya basicrassa was studied vitro. The compounds were found be able inhibit HIV-1 replication at different stages life cycle. Herewith, all exhibited significant antiviral by affecting early virus–cell interaction. fucoidan cichorioides showed highest virus-inhibitory blocking virus’ attachment entry into host’s cell, a selectivity index (SI) > 160.

Language: Английский

Citations

1
Prevalence of people living with multidrug‐resistant HIV and limited treatment options in Spain DOI
Josep M. Llibre, Féderico García, José Luís Blanco

et al.

HIV Medicine, Journal Year: 2024, Volume and Issue: 25(8), P. 946 - 957

Published: April 30, 2024

Abstract Objectives Our aim was to determine the prevalence and characteristics of people with HIV on antiretroviral therapy (ART) multidrug resistance (MDR; confirmed three or more [or two plus contraindication one more] core ART classes) limited treatment options (LTOs) in Spain. Methods This an observational, retrospective, multicentre, cross‐sectional chart review study undertaken five reference Spanish centres. Participants were MDR LTOs (detectable viral load [HIV‐RNA >200 copies/mL], treatment‐limiting drug–drug interaction [DDI], intolerance precluding use classes). Prevalence, demographic/clinical characteristics, assessed. Logistic regression analyses used identify MDR‐associated variables. Results Of 14 955 screened HIV, 69 (0.46%) presented 23 (0.15%) had LTOs. The population analysed 73.9% male a median age 54.0 years; time since diagnosis 26.5 years, CD4+ cell count 511.0 cells/μL. only factor significantly associated (univariate analysis) count. Injection drug most common transmission route. Comorbidities (mainly endocrine cardiovascular disorders; 34.8% affecting management) concomitant treatments frequent. No recent opportunistic infections reported. Patients been exposed following ART: nucleoside analogue reverse transcriptase inhibitors (100%), protease (95.6%), non‐nucleoside (87.0%), integrase strand transfer (82.6%). available fully active drugs dolutegravir (39.1%), bictegravir (30.4%), raltegravir (21.7%). Conclusions Spain is very low, approximately half those studied not exhibiting virological suppression. Low counts MDR. These findings may help address impact needs these patients prevent clinical progression HIV.

Language: Английский

Citations

0