HIV Mutation Detail Information

Virus Mutation HIV Mutation K70R


Basic Characteristics of Mutations
Mutation Site K70R
Mutation Site Sentence Table 1. Genotypic and phenotypic susceptibility of viruses harbouring NRTI and NNRTI resistance associated mutations (RAM).
Mutation Level Amino acid level
Mutation Type Nonsynonymous substitution
Gene/Protein/Region RT
Standardized Encoding Gene gag-pol:155348
Genotype/Subtype HIV-1 B
Viral Reference HXB2
Functional Impact and Mechanisms
Disease HIV Infections    
Immune -
Target Gene -
Clinical and Epidemiological Correlations
Clinical Information -
Treatment NRTI
Location -
Literature Information
PMID 40254262
Title Combined doravirine and islatravir cooperate to inhibit NRTI and NNRTI resistant HIV-1 in vitro
Author Giammarino F,Paletti C,Bartolini N,Fiaschi L,Biba C,Varasi I,Foca E,Gulminetti R,Ferrara M,Comi L,Vicenti I,Castagna A,Zazzi M,Saladini F
Journal Antiviral research
Journal Info 2025 Jul;239:106157
Abstract Doravirine and islatravir have shown promising activity against multidrug resistant HIV-1. In this study we aimed to evaluate the in vitro susceptibility to doravirine and islatravir as well as their combinatorial activity in a panel of 38 recombinant viruses harboring multiple NRTI and NNRTI mutations. One additional recombinant virus had the M184V mutation alone. According to the IC(50) fold-change (FC) values calculated with respect to the NL4-3 wild-type strain, full susceptibility to doravirine was detected in 15/39 (38.5 %) samples, while high-level resistance was mainly associated with specific doravirine resistance mutations. Decreased susceptibility to islatravir was associated with the presence of the M184V/I mutation and increasing numbers of TAMs and NRTI resistance mutations. According to ZIP model of the SynergyFinder Plus tool, the combination of doravirine and islatravir showed additive activity in 37/40 (92.5 %) viruses (including the NL4-3 strain), while synergy and antagonism in one and two cases, respectively. The combination sensitivity score calculated by SynergyFinder Plus indicated a cooperative effect between doravirine and islatravir higher than that observed for the reference NL4-3 strain in 22 (56 %) recombinant viruses. The Multi-dimensional Synergy of Combinations (MuSyC) tool predicted synergy and antagonism in 25 (62.5 %, including NL4-3 virus) and 15 (37.5 %) cases, respectively. MuSyC scores showed a negative correlation with doravirine FC values, number of NRTI mutations and presence of M184V/I, but not with islatravir FC values. Doravirine and islatravir may cooperatively inhibit NRTI and NNRTI resistant viruses despite complex mutational profiles, however the accumulation of resistance mutations may reduce the combinatorial activity.
Sequence Data -
Mutation Information
Note
Basic Characteristics of Mutations
  • Mutation Site: The specific location in a gene or protein sequence where a change occurs.
  • Mutation Level: The level at which a mutation occurs, including the nucleotide or amino acid level.
  • Mutation Type: The nature of the mutation, such as missense mutation, nonsense mutation, synonymous mutation, etc.
  • Gene/Protein/Region: Refers to the specific region of the virus where the mutation occurs. Including viral genes, viral proteins, or a specific viral genome region. If the article does not specifically indicate the relationship between the mutation and its correspondence, the main
  • Gene/Protein/Region studied in the article is marked.
  • Genotype/Subtype: Refers to the viral genotype or subtype where the mutation occurs. If the article does not specifically indicate the relationship between the mutation and its correspondence, the main Genotype/Subtype studied in the article is marked.
  • Viral Reference: Refers to the standard virus strain used to compare and analyze viral sequences.
Functional Impact and Mechanisms
  • Disease: An abnormal physiological state with specific symptoms and signs caused by viral infection.
  • Immune: The article focuses on the study of mutations and immune.
  • Target Gene: Host genes that viral mutations may affect.
Clinical and Epidemiological Correlations
  • Clinical Information: The study is a clinical or epidemiological study and provides basic information about the population.
  • Treatment: The study mentioned a certain treatment method, such as drug resistance caused by mutations. If the study does not specifically indicate the relationship between mutations and their correspondence treatment, the main treatment studied in the article is marked.
  • Location: The source of the research data.
Literature Information
  • Sequence Data: The study provides the data accession number.