HIV Flashcards
what are the name of the type of drug that stops binding of the virus to target cell?
fusion inhibitors can stop the binding of the CD4-R/co-receptor (CCR5) to the HIV
protease inhibitors work how?
they stop the action of the viral protease from cleaving proteins into active forms
therefore it stops the virus from getting out of the cell and infecting other cells. it does not however, stop that cell from getting destroyed (c.f. Reverse transc inhibs)
what is the current theory about why patients with HIV get chronic immune activation?
in the initial infection with HIV, there is profound loss of the GALT/peyer’s patches (and this only partially returns even with full treatment)
because of this, there is quite significant loss of the barrier, and then a lot of chronic minor infection, particularly as the bugs are then moved up to the LNs
what is the better predictor of rate of decline of immune function in asymptomatic patient?
HIV RNA concentration or CD4 count?
RNA concentration is better
despite this, markers of immune activation are actually better.
how does the HIV molecule get into the cell?
it binds with the CD4-R. there is a coreceptor which it also needs to bind with
typically this is the CCR5
in patients with specific genetics that lead to loss of CCR5 (e.g. delta32 homozygotes with no CCR5 expression) have resistance to R5 isolates
if delta32 heterozygote, then delated progression to AIDS
what is the treatment regimen of choice for HIV patients?
The optimal antiretroviral (ARV) regimen for a treatment-naive patient consists of two NRTIs in combination with a third active ARV drug from one of three drug classes: an NNRTI, a PI boosted with ritonavir, or an INSTI.
what are some of the agents that you might know about?
let’s talk nucleoside RTIs
Kivexa is a combined tablet
- abacavir and lamivudine
- this agent should not be used in patients with high CVS risk
- 5% of the population will have a hypersens to the abacavir. The way we check for this is the HLAB5701 (if pos, don’t use)
Truvada is a combined tablet
- this is tenofovir plus emtricitabine
- this is the drug of choice for Hep B co-infection (because these agents work against HBV)
what are the nNRTIs of choice?
Nevirapine
- do not use if CD4 counts are above 250 in women, or 400 in men
- this is because with high CD4 counts, it causes an increased risk of hep and rash.
Efavirenz
- popular
- potential teratogenicity
- caution if preggo
PI first line agents?
lopinavir
atazanavir
Each of these should be boosted with ritonavir
- ritonavir works by interacts with CYP-3A4 and leads to decreased hep clearance of other PIs.
- overall it leads to IMPROVED PHARMACOKINETIC PROFILE
what are some mandatory pre-treatment tests in HIV?
- HLA B5701 (abacavir)
- Genotype resistance assay
- Hep B serology
- Pregnancy counselling
- CVD risk calculated
what is the characteristics of the abacavir hypersens reaction?
within the first 6 weeks (usually)
fever rash fatigue malaise sore throat/cough myalgia
N/V/D
if this happens, stop immediately
do not rechallenge, for risk of anaphylactoid
what are some common toxicities seens with ART?
talk about NRTI
lipoatrophy (severe fat wasting) but better described as lipodystrophy because there is some central fat accumulation
MITOCHONDRIAL TOXICITY
peripheral neuropathy
renal disease - particularly tenofovir
zidovudine - N/V/headache/insomnia
what are some common toxicities seens with ART?
talk about nnRTI
rash and hepatitis
CNS toxicity - efavirenz causes this in almost all patients in the first few days of treatment, however it dissipates with time (this is usually nightmares and vivid dreams). Also dizziness (therefore give at night time)
SJ syndrome
what are some common toxicities seens with ART?
talk about PI
Metabolic complications such as hyperlipid and hyperglycaemia
CVS disease - this is ON TOP of the hyperlipid and hypergly (greater than expected for those RFs alone)
diarrhoea
jaundice is particularly common in ATA and IDV (?low yield?)
WHat does rifampicin do to some of the ART?
it decreases the level of PI
what does clarithromycin do to the ART?
it decreases the level of NNRTI
how are statins affects by a type of ART?
PI increase the level of statins, particularly simvastatin
The best choice is pravastatin which is not affected by this
which PI is affected by stomach acid?
atazanavir requires acidic environment to be well absorbed.
therefore, PPIs lead to poor absorption
how are inhaled steroids affected by which ART?
ritonavir leads to increased levels of fluticasone and eventually, Cushings
which ART is esp important in patients on methadone?
nevirapine leads to decreased levels of methadone
this can lead to clinically significant wirhdrawal
which drug affects the COCP?
nevirapine leads to decreased level of the oestrogen component of COCP
how does one manage the immune reconstitution inflammatory syndrome?
once drug toxicity and other differentials have been excluded, we continue ART
provide anti-inflamm
provide anti-microbial agents
you should aim to prevent it.
- if CD4 <50 should have ophthalm review prior to ART (CMV)
- CXR
- MAC should be checked for - faeces and blood specimens
- PCP prophylaxis
- complete cryptococcal Ag
- check for all the heps (serology and PCR)
consider MAC prophylaxis (?isoniazid)
how do we provide ART in pregnancy?
- mother should start ART at least in second trimester with aim for undetectable viral load at time of delivery (this is the most important for reducing vertical transmission)
- baby gets ART for first 6 weeks of life
- if viral load undetect = can have SVD
if any virus > must have C section - no breast feeding
transmission can still occur, about 2%. but significantly better than baseline 30%!
when do we need to start PEP?
how long do we continue it for?
what is the window period?
commence within 72 hours of exposure
ART should be continued for 4 weeks
the window period is extended to 6 months (there is a theory that the PEP could delay any possible seroconversion
what are very strong reasons INDEPENDENT OF CD4 for initiation of ART
pregnancy
history of AIDS defining illness
HIV associated nephropathy
HIV/hep B coinfection
how does the mitochondrial toxicity work?
it is particularly important in the nucleoside RTIs
this is because they are essentially DNA polymerase inhibitors. all of our cells are dependent on these. The major cellular DNA pol are not affected. However, the mitochondrial DNA pol are
this leads to adverse events such as:
lactic acidosis peripheral neuropathy CMP pancreatitis anaemia
the older agents were more problematic for this
d4T > ddI > AZT > ABC > 3TC
which of the ART is most important to consider renal function?
Tenofovir is a NRTI
it can lead to renal impairment
the MoA is not clear yet
therefore measure urine protein:creat ratio
what is the interplay between HIV and Hep C?
Hep C coinfection has little impact on the progression of HIV
HOWEVER,
HIV leads to higher HCV viral loads, more rapid progression and higher transmission
it is particularly difficult to assess the HCV when there is use of ART that can cause hepatotoxicity
what sort of symptoms does one see with HIV dementia?
what sort of syndrome
global findings, such as memory impairment, irritability, behavioural change, poor concentration and possibly motor symptoms like loss of fine motor control
however, focal things like dysphasia are less common
