HIV Flashcards
HIV PEP - First line treatment?
TDF/FTC + raltegravir 1200mg OD (400mg BD in pregnant women)
HIV PEP - definite indications for giving?
Sexual
- Receptive or insertive anal intercourse with HIV pos person with unknown or detectable HIV viral load
- Receptive anal intercourse from pt with unknown hiv status and from a high risk group
- Receptive vaginal intercourse with HIV pos pt with unknown or detectable HIV viral load
Occupational exposure
– Sharps injury or mucosal splash from someone with a detectable or unknown HIV viral load
Other
- People sharing drug injecting equipment if the index partner is known to be HIV pos with unknown or detectable HIV viral load
HIV PEP - baseline bloods
Creatinine
ALT
HBsAb, HBsAg, HBcAg
Hep C
HIV Ag/Ab
HIV PEP followup
HIV Ag/Ab - min 45 days after finishing PEP
Patient on PrEP who has had unprotected receptive anal sex with UK MSM. When should they get PEP?
Anal – for continuous PrEP where fewer than 4 pills taken in the prior 7 days or when on event based PEP where PrEP has not been taken as recommended
Patient on PrEP who has had unprotected receptive vaginal sex with person with known HIV and a viral load of >200. When should they get PEP?
PEP should be considered if >48h have elapsed since last dosing or one missed dose in the last 7 days
Vaccines contraindicated in HIV?
Absolute
- BCG
- Live typhoid
Consider only if CD4 >200
- Typhoid
- Small pox
- Live VZV (CP or shingles)
- Yellow fever
- MMR
Bands on Geenius
HIV 2
–Gp 36
–Gp 140
HIV 1
–Gp 31
–Gp 160
—-Cleaves to make gp 120 and gp 41
–P24
–Gp 41
Window period for 50th and 99th percentile for HIV 4th gen ag/ab test
45 and 90 days
Common HIV resistance mutations?
M184V - Resistance to lamivudine and emtricitabine
Hypersusceptibility to TDF/AZT
Plus viral fitness cost leads to around 0.5 log fall in viraemia
K65R - TDF resistance with cross resistance to abacavir and lamivudine
Hypersusceptibility to AZT
E138K - Rilpivirine - often seen alongside M184V/I and restores the viral fittness lost with that mutation
K103N - Efanvirenz and nevirapine resistance
HIV - K103N
Efanvirenz and nevirapine resistance
HIV - E138K
Rilpivirine - often seen alongside M184V/I and restores the viral fittness lost with that mutation
HIV - K65R
DF resistance with cross resistance to abacavir and lamivudine
Hypersusceptibility to AZT
HIV - M184V
Resistance to lamivudine and emtricitabine
Hypersusceptibility to TDF/AZT
Plus viral fitness cost leads to around 0.5 log fall in viraemia
HIV viral life cycle
Binding – gp120 binds either CXCR4 or CCR5
Fusion – gp41 binds heparan sulfate on cell plasma membrane and triggers fusion of the viral envelope
Reverse transcription – viral RNA released into cytoplasm following release from the capsid. Viral RNA reverse transcribed into cDNA by RT.
Integration – viral DNA is transported to the nucleus and randomly inserts into host genome – catalysed by the viral enzyme integrase
Replication – viral proteins are made. Several viral pre-proteins are made which are later cleaved in the maturation step to make smaller proteins. This is where protease drugs work. NB – gp120 and gp140 are cleaved from the bigger protein gp160. Gp160 and gp41 are both in the Geenius HIV1/2 biospot. Core proteins are initially translated into pr55 which is then cleaved to make p24 amongst others.
Assembly – Larger proteins migrate to the cell surface and implant into the plasma membrane to form the viral envelope. At this stage the virion is not infectious as the larger proteins have not yet been cleaved into functional proteins.
Budding – the virion crosses the plasma membrane to get is lipid envelope. The Gag proteins, along with the viral RNA and other enzymes, assemble at the inner surface of the host cell’s plasma membrane. The Gag proteins form a lattice-like structure that encapsulates the viral RNA and enzymes, creating a spherical core that will become the mature virion.
Maturation -The viral protease enzyme (which was packaged inside the virion during assembly) cleaves the Gag and Gag-Pol precursor proteins into smaller, functional pieces. This cleavage leads to the rearrangement of the viral proteins, which causes the virion to mature into a fully infectious form. Larger proteins are cleaved into smaller ones. This is where protease drugs work. NB – gp120 and gp140 are cleaved from the bigger protein gp160. Gp160 and gp41 are both in the Geenius HIV1/2 biospot. Core proteins are initially translated into pr55 which is then cleaved to make p24 amongst others.
