Meta-analysis and systematic review of the efficacy and resistance for human immunodeficiency virus type 1 integrase strand transfer inhibitors. 2019

Li-Li Yang, and Qi Li, and Li-Bo Zhou, and Shu-Qing Chen
Institute of Drug Metabolism and Pharmaceutical Analysis, College of Pharmaceutical Sciences, Zhejiang University, No. 866 Yuhangtang Road, Hangzhou 310058, China.

Integrase strand transfer inhibitors (INSTIs) are the most recent class of antiretroviral drugs with potent and durable antiviral activity used to treat human immunodeficiency virus type 1 (HIV-1) infection. However, development of drug resistance increases the risk of treatment failure, disease progression and mortality. A better understanding of drug efficacy and resistance against INSTIs is crucial for their efficient use and the development of new antiretrovirals. A meta-analysis of studies reporting efficacy and resistance data on INSTI use in HIV-infected patients was performed. Odds ratios (ORs) of efficacy outcome data favouring INSTI use in different clinical settings demonstrated that INSTIs have higher efficacy compared with drugs of other classes. For combination antiretroviral therapy-naïve patients and virologically-suppressed patients who switched to INSTI-based therapy, the OR was 1.484 (95% CI 1.229-1.790) and 1.341 (95% CI 0.913-1.971), respectively. ORs of resistance data indicated decreased treatment-emergent resistance development to dolutegravir (DTG) upon virological failure than to non-INSTIs (OR = 0.081, 95% CI 0.004-1.849), whereas the opposite was observed for raltegravir (RAL) (OR = 3.137, 95% CI 1.827-5.385) and elvitegravir (EVG) (OR = 1.886, 95% CI 0.569-6.252). Pooled analysis of resistance data indicated that development of resistance to DTG and bictegravir was rare, whereas EVG and RAL had low genetic barriers to resistance and the intensive cross-resistance between them limits INSTI efficiency. Efficient means of monitoring the emergence of resistance to INSTIs and the development of drugs with high genetic barriers are clear paths for future research.

UI MeSH Term Description Entries
D008826 Microbial Sensitivity Tests Any tests that demonstrate the relative efficacy of different chemotherapeutic agents against specific microorganisms (i.e., bacteria, fungi, viruses). Bacterial Sensitivity Tests,Drug Sensitivity Assay, Microbial,Minimum Inhibitory Concentration,Antibacterial Susceptibility Breakpoint Determination,Antibiogram,Antimicrobial Susceptibility Breakpoint Determination,Bacterial Sensitivity Test,Breakpoint Determination, Antibacterial Susceptibility,Breakpoint Determination, Antimicrobial Susceptibility,Fungal Drug Sensitivity Tests,Fungus Drug Sensitivity Tests,Sensitivity Test, Bacterial,Sensitivity Tests, Bacterial,Test, Bacterial Sensitivity,Tests, Bacterial Sensitivity,Viral Drug Sensitivity Tests,Virus Drug Sensitivity Tests,Antibiograms,Concentration, Minimum Inhibitory,Concentrations, Minimum Inhibitory,Inhibitory Concentration, Minimum,Inhibitory Concentrations, Minimum,Microbial Sensitivity Test,Minimum Inhibitory Concentrations,Sensitivity Test, Microbial,Sensitivity Tests, Microbial,Test, Microbial Sensitivity,Tests, Microbial Sensitivity
D010078 Oxazines Six-membered heterocycles containing an oxygen and a nitrogen.
D010879 Piperazines Compounds that are derived from PIPERAZINE.
D011728 Pyridones Pyridine derivatives with one or more keto groups on the ring. Pyridinones
D006575 Heterocyclic Compounds, 3-Ring A class of heterocyclic compounds that include a three-ring fused structure. Both aromatic or non-aromatic ring structures are included in this category. Fused Heterocyclic Compounds, Three-Ring,Heterocyclic Cpds, 3 Ring,Three Ring Heterocyclic Compounds,3-Ring Heterocyclic Compounds,Fused Heterocyclic Compounds, Three Ring,Heterocyclic Compounds, 3 Ring
D006576 Heterocyclic Compounds, 4 or More Rings A class of heterocyclic compounds that include four or more fused rings. Both aromatic or non-aromatic ring structures are included in this category. Heterocyclic Compounds with 4 or More Rings,Five Ring Heterocyclic Compounds,Four Ring Heterocyclic Compounds,Fused Heterocyclic Compounds, Five-Ring,Fused Heterocyclic Compounds, Four-Ring,Heterocyclic Compounds with Four or More Rings,Heterocyclic Compounds, 4-Ring,Heterocyclic Compounds, 5-Ring,Heterocyclic Cpds, 4 Ring,Heterocyclic Cpds, 4 or More Rings,Heterocyclic Cpds, 5 Ring,4-Ring Heterocyclic Compounds,5-Ring Heterocyclic Compounds,Fused Heterocyclic Compounds, Five Ring,Fused Heterocyclic Compounds, Four Ring,Heterocyclic Compounds, 4 Ring,Heterocyclic Compounds, 5 Ring
D006801 Humans Members of the species Homo sapiens. Homo sapiens,Man (Taxonomy),Human,Man, Modern,Modern Man
D000068898 Raltegravir Potassium A pyrrolidinone derivative and HIV INTEGRASE INHIBITOR that is used in combination with other ANTI-HIV AGENTS for the treatment of HIV INFECTION. Isentress,MK 0518,MK-0518,MK0518,Raltegravir,0518, MK,Potassium, Raltegravir
D000577 Amides Organic compounds containing the -CO-NH2 radical. Amides are derived from acids by replacement of -OH by -NH2 or from ammonia by the replacement of H by an acyl group. (From Grant & Hackh's Chemical Dictionary, 5th ed) Amide
D014779 Virus Replication The process of intracellular viral multiplication, consisting of the synthesis of PROTEINS; NUCLEIC ACIDS; and sometimes LIPIDS, and their assembly into a new infectious particle. Viral Replication,Replication, Viral,Replication, Virus,Replications, Viral,Replications, Virus,Viral Replications,Virus Replications

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