HIV Mutation Detail Information

Virus Mutation HIV Mutation L74I


Basic Characteristics of Mutations
Mutation Site L74I
Mutation Site Sentence HLA genotypes A *02:01/05/14, B *44:15, and C *04:07 predicted the presence of L74I, a mutation recently observed in association with long-acting INSTI cabotegravir virologic failure.
Mutation Level Amino acid level
Mutation Type nonsynonymous substitution
Gene/Protein/Region IN
Standardized Encoding Gene gag-pol:155348
Genotype/Subtype HIV-1 A1
Viral Reference HXB2
Functional Impact and Mechanisms
Disease HIV Infections    
Immune -
Target Gene -
Clinical and Epidemiological Correlations
Clinical Information Y
Treatment INSTIs
Location Uganda
Literature Information
PMID 33635845
Title Pre-treatment integrase inhibitor resistance is uncommon in antiretroviral therapy-naive individuals with HIV-1 subtype A1 and D infections in Uganda
Author McCluskey SM,Kamelian K,Musinguzi N,Kigozi S,Boum Y 2nd,Bwana MB,Muzoora C,Brumme ZL,Carrington M,Carlson J,Foley B,Hunt PW,Martin JN,Bangsberg DR,Harrigan PR,Siedner MJ,Haberer JE,Lee GQ
Journal AIDS (London, England)
Journal Info 2021 Jun 1;35(7):1083-1089
Abstract OBJECTIVE: Dolutegravir (DTG) is now a preferred component of first-line antiretroviral therapy (ART). However, prevalence data on natural resistance to integrase inhibitors [integrase strand transfer inhibitors (INSTIs)] in circulating non-subtype B HIV-1 in sub-Saharan Africa is scarce. Our objective is to report prevalence of pre-treatment integrase polymorphisms associated with resistance to INSTIs in an ART-naive cohort with diverse HIV-1 subtypes. DESIGN: We retrospectively examined HIV-1 integrase sequences from Uganda. METHODS: Plasma samples were derived from the Uganda AIDS Rural Treatment Outcomes (UARTO) cohort, reflecting enrollment from 2002 to 2010, prior to initiation of ART. HIV-1 integrase was amplified using nested-PCR and Sanger-sequenced (HXB2 4230-5093). Stanford HIVdb v8.8 was used to infer clinically significant INSTI-associated mutations. Human leukocyte antigen (HLA) typing was performed for all study participants. RESULTS: Plasma samples from 511 ART-naive individuals (subtype: 48% A1, 39% D) yielded HIV-1 integrase genotyping results. Six out of 511 participants (1.2%) had any major INSTI-associated mutations. Of these, two had E138T (subtype A1), three had E138E/K (subtype D), and one had T66T/I (subtype D). No participants had mutations traditionally associated with high levels of INSTI resistance. HLA genotypes A *02:01/05/14, B *44:15, and C *04:07 predicted the presence of L74I, a mutation recently observed in association with long-acting INSTI cabotegravir virologic failure. CONCLUSION: We detected no HIV-1 polymorphisms associated with high levels of DTG resistance in Uganda in the pre-DTG era. Our results support widespread implementation of DTG but careful monitoring of patients on INSTI with virologic failure is warranted to determine if unique mutations predict failure for non-B subtypes of HIV-1.
Sequence Data MH925338-MH925677;MW341596-MW341779
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.