HIV Mutation Detail Information

Virus Mutation HIV Mutation M184V


Basic Characteristics of Mutations
Mutation Site M184V
Mutation Site Sentence One strategy has been using 3TC/ FTC monotherapy (3TC/FTC), which in the presence of the M184V resistance mutation, does not suppress viral replication nor select for additional drug resistance mutations, and reduces viral fitness with limited side effects.
Mutation Level Amino acid level
Mutation Type Nonsynonymous substitution
Gene/Protein/Region RT
Standardized Encoding Gene gag-pol:155348
Genotype/Subtype HIV-1
Viral Reference -
Functional Impact and Mechanisms
Disease HIV Infections    
Immune Y
Target Gene -
Clinical and Epidemiological Correlations
Clinical Information -
Treatment NRTIs
Location America;Thailand
Literature Information
PMID 28604824
Title Decline in CD4 T lymphocytes with monotherapy bridging strategy for non-adherent adolescents living with HIV infection: Results of the IMPAACT P1094 randomized trial
Author Agwu AL,Warshaw MG,McFarland EJ,Siberry GK,Melvin AJ,Wiznia AA,Fairlie L,Boyd S,Harding P,Spiegel HML,Abrams EJ,Carey VJ
Journal PloS one
Journal Info 2017 Jun 12;12(6):e0178075
Abstract INTRODUCTION: Management of persistently non-adherent youth living with HIV (YLHIV) with virologic failure (VF) on combination antiretroviral therapy (cART) remains challenging. One strategy has been using 3TC/ FTC monotherapy (3TC/FTC), which in the presence of the M184V resistance mutation, does not suppress viral replication nor select for additional drug resistance mutations, and reduces viral fitness with limited side effects. P1094 compared the immunologic outcome of continuing failing cART vs. switching to 3TC/FTC as a ""bridging strategy"" to subsequent suppressive cART for non-adherent YLHIV with pre-existing M184V resistance. MATERIALS & METHODS: Participants with documented nonadherence, M184V mutation, CD4+ T cell count >/=100 cells/mm3 and VF (HIV-1 plasma RNA >/=400 copies/mL (2.6 log10 HIV-1 RNA) were enrolled and randomized to continue failing cART vs. switch to 3TC/FTC. The primary endpoint (time to >/=30% CD4+ T cell decline or development of CDC class C events) at 28-weeks were assessed by Kaplan-Meier (K-M) curves in an intent-to-treat analysis. RESULTS: Thirty-three perinatally acquired YLHIV participants (16 continuing cART and 17 3TC/FTC) enrolled in the study. The median age, entry CD4+ T cell count, and viral load were 15 years (Inter-quartile range (IQR) 14-20), 472 cells/mm3 (IQR 384-651), and 4.0 log10HIV-1 RNA copies/ml (IQR 3.2-4.5), respectively. Five participants, all in the 3TC/FTC arm, reached the primary endpoint for absolute CD4+ T cell decline (p = 0.02, exact log-rank test comparing monotherapy to cART). The Kaplan-Meier estimate of probability of primary endpoint on 3TC/FTC at 28 weeks was 0.41 (standard error 0.14). There were no CDC class C events or deaths and no statistically significant difference in frequencies of adverse events between the arms. CONCLUSIONS: Non-adherent participants randomized to 3TC/FTC were more likely than those maintained on failing cART to experience a confirmed decline in CD4+ count of >/=30%. Although this study suffers from limitations of small sample size and premature discontinuation, the randomized comparison to continuing failing cART indicates that 3TC/FTC provides inferior protection from immunologic deterioration for non-adherent youth with M184V resistance. Better alternatives to 3TC/FTC such as ART with higher barriers to resistance and novel adherence and treatment strategies for nonadherent youth are urgently needed. TRIAL REGISTRATION: Clinical Trials.gov NCT01338025.
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.