HIV
Koja su jedinstvena svojstva strukture i replikacije retrovirusa?
- diploidni genom
- integracija provirusne DNK u genom inficirane ćelije kao obavezan korak replikacije
Objasniti nomenklaturu mutacija
G48V
broj označava poziciju kodona/AK
slova označavaju AK u wt (levo) i u mutiranom soju (desno)
Navedi metode za određivanje ARV rezistencije
genotipsko određivanje rezistencije
- DNK sekvenciranje
- "Sanger" ili "NGS"
fenotipsko određivanje rezistencije
What is the difference between primary/baseline resistance testing and pretreatment resistance testing
Baseline resistance testing and pretreatment resistance testing both involve assessing drug resistance before starting treatment, with "pretreatment" referring to resistance at the point of starting a new regimen, and "baseline" meaning the resistance present at the initial diagnosis of infection.
Šta su HIV-1 podtipovi ?
Koliko ih ima i po čemu se razlikuju?
HIV-1 se svrstava u 4 grupe: M, N, O i P.
Grupa M se deli u 9 podtipova: A, B, C, D, F, G, H, J i K;
Novi HIV-1 M podtip L!
Koja je razlika između major i minor mutacija rezistencije?
Major mutacije uzrokuju funkcionalne promene koje dovode do rezistencije
Minor mutacije utiču na RC
How do we interpret results of genotypic HIV DR tests?
Interpretation of HIV DR relies on bioinformatic algorithms that link the obtained genotypic result to large databases of genotypic results corelated to phenotypic results and/or clinical outcomes (e.g. Stanford Drug Resistance Database) and are based on interpretation rules that include list of known mutations (e.g. the IAS-USA guidelines)
According to current guidelines, when should resistance testing be performed?
-Baseline genotypic resistance test should be performed on the first available sample at diagnosis
-Genotypic resistance testing is recommended prior to initiation of ART
-Resistance testing should be performed at virological failure
Šta označava pojam "kvazispecijesi"
Sojeve HIV-1 unutar inficiranog organizma
Koja od navedenih rečenica je tačna?
Rezistencija se ne javlja kod osoba koje nisu na terapiji
Rezistencija je uvek povezana sa lođom adherencom
Mutacije rezistencije se razlikuju u različitim podtipovima virusa
Unakrsna rezistencija među klasama ARV je česta pojava
Mutacije rezistencije se razlikuju u različitim podtipovima virusa
What are the indications for proviral DNA resistance testing?
1. Repeated failure of RNA amplification at baseline or time of virologic failure, especially at lower levels of viremia when amplification of HIV-RNA may fail.
2. A switch to a new regimen in individuals who are virally suppressed in the absence of a clearly documented treatment history, or insufficient access to historic resistance tests performed at baseline or during previous failure
3. The initiation of therapy in individuals not on ART, since in the absence of selective pressure, resistant variants may be archived in the DNA but replaced in the plasma by more replication-competent variants with less or no resistance.
On the basis of current data, which is most accurate regarding acquired drug resistance?
-Delaying ART initiation is associated with increased risk for acquired drug resistance
-If therapy is deferred, repeat testing at ART initiation to identify drug resistance is unnecessary
- Similar rates of acquired drug resistance have been shown with immediate and delayed ART initiation
- The rates of acquired drug resistance are significantly lower with immediate/early ART initiation vs delayed initiation
"Similar rates of acquired drug resistance have been shown with immediate and delayed ART initiation"
Navedite tri mehanizma u osnovi HIV varijabilnosti
1. RT visoka stopa mutacija
2. Rekombinacija
3. APOBEC uslovljena mutageneza
Po čemu je posebna mutacija RT M184V?
Navesti tri prednosti Sanger metode za ARV rezistenciju
•Well-established analytical method in every molecular laboratory with a variety of in house and commercial assays (decades of clinical experience)
•Bioinformatic algorithms with easily interpreted and highly reproducible results of HIV drug resistance
•Good performance regarding different molecular forms of HIV
•An impressive number of sequences available in genomic databases freely available to the scientific community
TRUE or FALSE
It is possible for individuals who have received preexposure prophylaxis to develop pretreatment drug resistance
TRUE
The prevalence of pre-exposure prophylaxis (PrEP)-associated resistance (defined as resistance to tenofovir and/or lamivudine) is low for individuals who acquire HIV while receiving tenofovir-containing PrEP. However, the prevalence of tenofovir and or lamivudine resistance is more than 10-fold higher if PrEP is initiated during undiagnosed acute HIV infection.
Kako glasi aktuelan taksonomski naziv virusa HIV-1 prema ICTV (International Committee on Taxonomy of Viruses)
Lentivirus humindef1
TAČNI ili NETAČNO
sve mutacije rezistencije javljaju se u ciljnim genima za specifične virusne genske produkte
NETAČNO
3’PPT: potential sequencing target in patients failing INSTI without adherence issues and no resistance based on pol region sequencing
Env region: potential relevance in patients with unexplained INSTI failure, highly diverse region
navesti tri prednosti NGS u odnosu Sanger metodu sekvenciranja za ARV rezsitenciju
-ability to detect low-frequency drug-resistant variants (LA-DRVs)
-high throughput and efficiency - NGS enables the simultaneous sequencing of millions of DNA fragments in a single run
-easier to access whole genome and test for resistance across multiple drug targets
Which statement best describes a recommendation for HIV drug resistance testing?
Drug resistance testing should be performed for all patients who are changing ART regimens regardless of their HIV viral load
ART initiation should be delayed while awaiting resistance testing results in patients who are pregnant and have HIV
In the setting of virologic failure, drug resistance testing is recommended within 6 weeks after discontinuing therapy
Results of drug resistance testing must be factored into the adjustment of ART regimens in patients experiencing virologic failure
"Results of drug resistance testing should be factored into the adjustment of ART regimens in patients experiencing virologic failure"