HIV Mutation Detail Information

Virus Mutation HIV Mutation K219Q


Basic Characteristics of Mutations
Mutation Site K219Q
Mutation Site Sentence Of note, TAMs-1 were predominant (T215F/Y: 46.5%;M41 L: 22.8%; L210 W: 8.9%) and associated with higher levels of resistance to both AZT and TDF;as compared to TAMs-2 that had relatively lower prevalence (D67N: 21.8%;K70R: 19.8%; K219Q/E: 18.8%) and were associated preferentially with AZT/D4T-resistance.
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 -
Target Gene -
Clinical and Epidemiological Correlations
Clinical Information -
Treatment stavudine (D4T);zidovudine (AZT)
Location Cameroon
Literature Information
PMID 30871487
Title HIV-1 drug resistance testing is essential for heavily-treated patients switching from first- to second-line regimens in resource-limited settings: evidence from routine clinical practice in Cameroon
Author Takou D,Fokam J,Teto G,Santoro MM,Ceccherini-Silberstein F,Nanfack AJ,Sosso SM,Dambaya B,Salpini R,Billong SC,Gori C,Fokunang CN,Cappelli G,Colizzi V,Perno CF,Ndjolo A
Journal BMC infectious diseases
Journal Info 2019 Mar 12;19(1):246
Abstract BACKGROUND: With the phase-out of stavudine (d4T), change to first-line regimens with zidovudine (AZT) or tenofovir (TDF) in resource-limited settings (RLS) might increase risks of cross-resistance to nucleos(t) ide reverse transcriptase inhibitors (NRTI). This would restrict the scope of switching to the World Health Organisation (WHO)-recommended standard second-line combinations (SLC) without HIV drug resistance (HIVDR)-testing in routine clinical practice. METHODS: An observational study was conducted among 101 Cameroonian patients (55.4% male, median [IQR] age 34 [10-41] years) failing first-line antiretroviral therapy (ART) in 2016, and stratified into three groups according to NRTIs exposure: exposure to both thymidine analogues AZT ""and"" D4T (group-A, n = 55); exposure to both TDF and AZT ""or"" D4T (group-B, n = 22); exposure solely to D4T (group-C, n = 24). Protease-reverse transcriptase HIVDR was interpreted using the HIVdb penalty scores (>/=60: high-resistance; 20-59: intermediate-resistance; < 20: susceptible). The acceptable threshold for potential-efficacy was set at 80%. RESULTS: The median [IQR] CD4, viral RNA, and time on ART, were respectively 129 [29-466] cells/mul, 71,630 [19,041-368,000] copies/ml, and 4 [2-5] years. Overall HIVDR-level was 89.11% (90/101), with 83.2% harbouring M184 V (high-level 3TC/FTC-resistance) and only 1.98% (2/101) major HIVDR-mutations to ritonavir-boosted protease-inhibitors (PI/r). Thymidine-analogue mutations (TAMs)-1 [T215FY (46.53%), M41 L (22.77%), L210 W (8.91%)], with cross-resistance to AZT and TDF, were higher compared to TAMs-2 [D67N (21.78%), K70R (19.80%), K219QE (18.81%)]. As expected, K65R was related with TDF-exposure: 0% (0/55) in group-A, 22.72% (5/22) group-B, 4.17% (1/24) group-C (p = 0.0013). The potential-efficacy of AZT vs. TDF was respectively 43.64% (24/55) vs. 70.91% (39/55) in group-A (p = 0.0038); 63.64% (14/22) vs. 68.28% (15/22) in group-B (p = 1.0000); and 37.50% (9/24) vs. 83.33% (20/24) in group-C (p = 0.0032). CRF02_AG was the prevailing subtype (63.40%), followed by CRF11.cpx (8.91%), A(1) (7.92%), G (5.94%); without any significant effect of the subtype-distribution on HIVDR (92.2% in CRF02_AG vs. 83.8% in non-AG; p = 0.204). CONCLUSION: First-line ART-failure exhibits high-level NRTI-resistance, with potential lower-efficacy of AZT compared to TDF. Significantly, using our 80% efficacy-threshold, only patients without NRTI-substitution on first-line could effectively switch to SLC following the WHO-approach. Patients with multiple NRTI-substitutions (exposed to both thymidine-analogues and TDF) on first-line ART would require HIVDR-testing to select active NRTIs for SLC.
Sequence Data JF273951; JF273953; JF273955; JF273957; JQ796149; JQ796150; JF273961; JF273962; JF273965; JQ796152; JQ796153; JQ796154; JQ796155; JQ796156; JQ796157; JQ796158; JQ796159; JQ796160; KR229828; JQ796163; JF273935; JF273936; JQ796168; JQ796169
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.