HIV Flashcards
What are the structural genes in HIV? Which is sequenced for resistance testing? Which encodes gp41 and gp120? Which encodes the core and matrix proteins?
gag, pol and env
pol encodes the RT, integrase, and protease
env encodes the surface glycoproteins
gag encodes core and matrix
What are the receptors for HIV?
gp120 binds to CD4 and uses CCR5 as a co-receptor (or CXCR4 in later infection)
What is the epidemic strain of HIV?
HIV-1, group M. Sub-type B (historically in MSM)
What percentage of patients will have HIV meningitis at seroconversion?
5-10% (or up to 30% in some papers)
What is the window period for HIV-1 in 4th generation assays?
45 days
What is the window period for HIV-1 in Western Blot?
90 days
Which HIV-2 bands are present on the BioRad Geenius?
Only envelope bands - gp36 and gp140
What bands are present in an HIV-1 Western blot?
env = gp160 (precursor), gp120, gp41
gag = p55 (precursor), p24 (core), matrix (p17), nucleocapsid (p15)
pol = p66 and p51 (RT) and p31 endonuclease
Which bands on the WB come up the earliest, and which the latest?
p24 and p55 (it’s precursor) come up earliest
p31 comes up latest (Fiebig lab stage 6)
What is the conversion of HIV copies/ml to IU/ml
Around 0.6 copies = 1 IU but it is assay dependent
Name some commonly used NRTIs
Zidovudine, emtricitibine, abacavir, lamivudine, TDF, TAF
Name some commonly used NNRTIs
Doravirine, efavirenz, neviripine, rilpirivine
How are integrase inhibitors and protease inhibitors identified by their names?
Integrase strand transfer inhibitors = -gravir
Protease inhibitors = - navir
What are HIV ‘booster drugs’? Give two examples
Used at subtherapeutic doses to inhibit cytochrome P450 (CYP3A) and increase half life
Cobicistat and ritonavir
Which drug is a CCR5 inhibitor? What testing is needed before this is prescribed? What would make CCR5 inhibitors ineffective?
Miraviroc
Testing is performed to see if HIV is CCR5 tropic (performed on whole blood - sequencing V3 loop)
If CXCR4 or dual tropic, miraviroc is not indicated
Name examples of HIV - fusion inhibitors, attachment inhibitors, post-attachment inhibitors, capsid inhibitors
Enfuvirtide
Fostemsavir
Ibalizumab
Lenacapavir
What HIV drugs are available as long acting injectables?
How often is it given?
How often do you need to have VLs?
What genotype is contraindicated?
Cabotegravir and rilpivirine
Injection every 8 weeks and VL every 8 weeks
Not for use in A1/6 genotype
Cabotegravir is an analogue of dolutegravir
What are first line treatments for HIV?
Bictegravir/emtricitibine/TAF
Dolutegravir/emtricitibine/TDF or TAF
Dolutegravir/lamivudine/abacavir
Dolutegravir/lamivudine (not if HBV)
Which class of HIV drug have the lowest and highest barrier to resistance?
Lowest = NNRTIs (only require 1 or 2 mutations)
Highest = Boosted PIs
What region of the genome is sequenced for drug resistance?
pol (RT and protease at baseline)
When is integrase resistance tested for?
When any mutation in other drug classes
Diagnosed in pregnancy
?transmitted INSTI resistance
Failing on INSTI treatment
What is defined as HIV virological failure?
<1 log reduction in VL after 4 weeks
> 200 copies/ml on two samples
What database is used for cumulative resistance reports?
Stanford Database
What level of HIV resistance mutation can Sanger and NGS detected?
20-25%
0.1-1%