|
Basic Characteristics of Mutations
|
|
Mutation Site
|
V75M |
|
Mutation Site Sentence
|
Table 2.Participants with L74I and longitudinal sampling |
|
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
|
K03455.1
|
|
Functional Impact and Mechanisms
|
|
Disease
|
HIV Infections
|
|
Immune
|
- |
|
Target Gene
|
-
|
|
Clinical and Epidemiological Correlations
|
|
Clinical Information
|
Y |
|
Treatment
|
RTIs |
|
Location
|
Nigeria |
|
Literature Information
|
|
PMID
|
32105319
|
|
Title
|
High prevalence of integrase mutation L74I in West African HIV-1 subtypes prior to integrase inhibitor treatment
|
|
Author
|
El Bouzidi K,Kemp SA,Datir RP,Murtala-Ibrahim F,Aliyu A,Kwaghe V,Frampton D,Roy S,Breuer J,Sabin CA,Ogbanufe O,Charurat ME,Bonsall D,Golubchik T,Fraser C,Dakum P,Ndembi N,Gupta RK
|
|
Journal
|
The Journal of antimicrobial chemotherapy
|
|
Journal Info
|
2020 Jun 1;75(6):1575-1579
|
|
Abstract
|
OBJECTIVES: HIV-1 integrase inhibitors are recommended as first-line therapy by WHO, though efficacy and resistance data for non-B subtypes are limited. Two recent trials have identified the integrase L74I mutation to be associated with integrase inhibitor treatment failure in HIV-1 non-B subtypes. We sought to define the prevalence of integrase resistance mutations, including L74I, in West Africa. METHODS: We studied a Nigerian cohort of recipients prior to and during receipt of second-line PI-based therapy, who were integrase inhibitor-naive. Illumina next-generation sequencing with target enrichment was used on stored plasma samples. Drug resistance was interpreted using the Stanford Resistance Database and the IAS-USA 2019 mutation lists. RESULTS: Of 115 individuals, 59.1% harboured CRF02_AG HIV-1 and 40.9% harboured subtype G HIV-1. Four participants had major IAS-USA integrase resistance-associated mutations detected at low levels (2%-5% frequency). Two had Q148K minority variants and two had R263K (one of whom also had L74I). L74I was detected in plasma samples at over 2% frequency in 40% (46/115). Twelve (26.1%) had low-level minority variants of between 2% and 20% of the viral population sampled. The remaining 34 (73.9%) had L74I present at >20% frequency. L74I was more common among those with subtype G infection (55.3%, 26/47) than those with CRF02_AG infection (29.4%, 20/68) (P = 0.005). CONCLUSIONS: HIV-1 subtypes circulating in West Africa appear to have very low prevalence of major integrase mutations, but significant prevalence of L74I. A combination of in vitro and clinical studies is warranted to understand the potential implications.
|
|
Sequence Data
|
-
|
|
|