HIV Flashcards
what type of virus is HIV?
single stranded RNA Lentivirus
variants of HIV
HIV-1 - more virulent, most common
HIV-2 - less common, W Africa
How is HIV transmitted?
- sex without condom
- from mother to baby during childbirth
- sharing needles
- contaminated blood transfusion/organ transplant
How to diagnosie HIV?
- POCT - point of care testing
- 4th generation assay
POCT - point of care test
- HIV Ab test
- finger prick test or mouth swab
- results in 20-30mins
- highly accurate >6 weeks after exposure
- less sensitive (+ve results send for 4th gen test)
4th generation assay
- HIV Ab and P24 Ag test
- blood sample sent to lab
- results can take 7 days
- highly sensitive after 4 weeks
What is P24 antigen that 4th generation assay looks for?
protein produced 2-3 weeks after infection
Markers to monitor HIV
- CD4 count
- viral load
CD4 count
no of CD4+ T cells in 1ul of blood
represents how well the immune system is functioning
CD4% represents proportion of CD4+ cells in relation to other WBC
Tx aim = inc CD4 count/CD4%
CD4 levels in normal and HIV
normal CD4 = 500-1000
normal CD4% = > 14
HIV CD4 = less than that
CD4 <350 inc risk infection
CD4 <200 severe risk
What is viral load?
- no. of copies of HIV RNA in 1ml of blood
- represents the conc of virus in the blood, not the amount of virus in the patient’s body
- Tx aim = dec VL to undetectable (<50-20)
Tx aims for CD4 and VL?
CD4 as high as possible
VL as low as possible
markers used to assess effectiveness of ARV Tx?
viral load
CD4 count
Reduced viral load leads to what CD4?
inc CD4 cell count or %
stages of HIV infection
- acute infection
- clinical latency
- declining CD4 count
acute infection stage (seroconversion illness)
- 1-6 weeks
- inc infectiousness, high viral load
- unaware of HIV status
- up to 50% asymptomatic
- non-specific Sx, flu-like
- diagnosis often missed
clinical latency stage
- declining CD4 count
- may last >8yrs
- some decline rapidly (6-12mths)
- non-progressors, never see decline in CD4 count
- stable viral load
- asymptomatic, few Sx, mild
- may be unaware of infection
risks with declining CD4 count
inc risk of opportunistic infection and lymphomas
AIDS
advanced immuno deficiency syndrome
When is AIDS diagnosed?
low CD4 count and at least 1 AIDS defining illness
- opportunistic infections
- cancers
PCP
P jirovecci pneumonia
Sx of PCP
- seen in new HIV diagnoses
- non productive cough and exertional dyspnoea, thick mucous
- weight loss
Tx for PCP
co-trimoxazole for 21 days
- IV for severe
- oral for mild/mod
(trimethoprim + sulfametoxazole)
prophylactic Tx for CD4 <200
co-trimoxazole 480mg OD PO
When to stop prophylactic Tx if CD4 <200?
when CD4 >200 for > 3 months
MAC
mycobacterium avium complex
Sx of MAC
fever
night sweats
fatigue
weight loss
anorexia
diarrhoea
Tx of MAC
macrolides + ethambutol
prophylactic Tx for MAC
azithromycin 1250mg WEEKLY
Mycobacterial TB Tx
pyrazinamide
rifampicin
ethambutol
isoniazid
What has inc risk with mycobacterium TB?
risk of IRIS
malignancies at inc risk with HIV
- systemic NHL
- primary cerebral - lymphoma
- Kaposi’s sarcoma
- cervical cancer
enzymes in HIV virus not found in humans
reverse transcriptase
integrase
protease
4 types of HIV drugs
- CCR5 inhibitors
- nucleoside/nucleotide RT inhibitors &non-nucleoside RTIs
- integrase inhibitors
- protease inhibitors
goals of HIV Tx
- etended life expectancy and QOL
- preserve and restore CD4 cell count
- viral load undetectable within 4-6mths (<20 copies/ml)
- prevent transmission
when to start Tx (4)
- primary infection
- chronic infection
- presents ith AIDS or major infection
- prevention of transmission
When to start Tx in primary infection?
only when patient ready, uness:
- neurological involvelemt
- any AIDS defining illness
- CD4 persistently <350 cells/ul
- diagnosis within 12 weeks of previous negative
When to start Tx if patient presents with AIDS/major infection?
start within 2 weeks of antimicrobials if
- AIDS defining infection
- serious bacterial infection with CD4 count <200 cells/ul
pros of early Tx
- inc immunological recovery
- reduced transmission
- reduced disease progression/morbidity
- reassurance to pt
cons of early Tx
- not prepared for Tx, poor adherence leads to resistance
- cost
- LT s/e
factors to consider when starting Tx
- CD4 count
- viral load
- pt’s likely adherence
- discordant couples where 1 has high VL
- transmission risk
- pregnancy
- pt’s wishes
- co-morbidities (AIDS, HepB/C, TB, neuro involvement, CVD risk, IRIS risk)
IRIS
immune reconstitution inflammatory syndrome
What is IRIS?
- starting ART, immune system recovers
- get infection, immune system can over react, high inflammatory response
- can be fatal
- treat the infection first, then start HIV meds, don’t start at same time as ART
patient factors to consider before starting Tx
- renal, liver fxn
- CV risk
- pregnancy
- drug Hx, oral contraceptives
- pill burden
- psychiatric, mental health
- concurrent infections (HepC, TB)
- Tx experienced or naive
- adherance
- pt choice
- allergies
- viral load
2 types of ARV prophylaxis Tx?
- PEP - post exposure prophylaxis
- PrEP - preexposure prophylaxis
post exposure prophylaxis - PEP
28 days Tx started within 72hrs after exposure
sexual, needle stick injury
pre-exposure prophylaxis - PrEP
taken daily or PRN by HIV -ve person to prevent transmission
high risk, unprotected sex
What drugs are used as the backbone drugs?
NRTI
- tenofovir and emtricitabine
- abacavir and lamivudine
What are the NRTI backbone combined with?
protease inhibitors
OR
integrase inhibitors
OR
NNRTIs
rarely CCR5 inhibitors
What are always used with protease inhibitors?
always boosted with either cobicistat OR ritonavir
- CYP inhibitors
- inhibit metabolism of protease inhibitors by liver
- lower doses, give less frequently, less s/e
How to NRTIs work?
block addition of nucleosides to DNA chain during transcription
terminate building of DNA chain
pros and cons of Truvada (tenofovir disoproxil fumarate & emtricitabine)
pro - 1st line, good at reducing VL
cons - tenofovir associated with kidney disease (caution CKD stage 3), LT effects on bone density
- dec CrCl (<60) –> avoid
- Hx bone density problems, OP –> AVOID
pros and cons of Descovy (tenofovir alafenamide & emtricitabine)
pros - equivalent to Truvada, benefit over Truvada if renal/bone disease
cons - very expensive, NEW
pros and cons of Kivexa (abacavir & lamivudine)
pros - 2nd line, HLAB 5701 negative, no effect on BMD/renal fxn, only use if VL <100,000
cons - caution in CVD
cautions when using Truvada (tenofovir + emtricitabine)
CKD stage 3
low BMD - OP
cautions when using Kivexa (abacavir + lamividuine)
CVD
Tenofovir salts
TDF = tenofovir disoproxil fumarate (Truvada)
TAF = temofovir alafenamide (Descovy)
difference between TDF and TAF
both prodrugs
TDF activated in plasma
TAF activated intracellulary
- lower plasma concs
- fewer s/e (BMD, renal fxn)
Abacavir problems
- allergy, fatal allergic rxn
- CANNOT GIVE if +ve for HLA-B 5701 gene - significant CVD risk
- cautioned - high viral load, >100,000
- not as effective
test before giving Abacavir
HLA-B 5701 gene
formulation of Abacavir that CAN be used if high VL
Triumeq (if co-formulated with this)
pros and cons of protease inhibitors
pros
- high barrier to resistance (good if not adherent)
- effective
cons
- a lot of interactions (enzyme inhibitors, CYP)
- cost (expensive)
- a LOT OF S/E (redistribution of body lipids)
pros and cons of integrase inhibitors
pros
- few s/e
- few interactions (Ca, Mg supplements)
- rapid dec in VL, response rapid
cons
- cost
- low barrier to resistance
pros and cons of NNRTIs
pros
- were 1st line
- effective
- few s/e
cons
- psychiatric problems
- c/i if Hx mental health problems
- rilpivirine only if VL<100,000
- interactions
- low barrier to resistance
resons for Tx failure
- resistance
- poor adherence (s/e, forgetting, lifestyle)
- drug interactions (Rx or OTC)
How often is VL measured when established on Tx?
about every 6 months
How often is VL measured when established on Tx?
about every 6 months
When to do resistance testing for HIV drugs?
- initiation
- change
- Tx failure
What % adherence is needed?
> 95%
(only missing 1 dose per month)
risks associated with poor adherence
- risk of Tx failure
- disease progression
- transmission of resistant virus
- inc healthcare costs
What enzyme is used to convert HIV RNA to DNA?
reverse transcriptase
How does resistance occur?
- reverse transcriptase is prone to errors
- 1 in 10,000 bases of viral RNA
- leads to mutationos
- can lead to resistance, inc sensitivtity or have no effect on the drug
What is WT HIV?
HIV without any genetic mutations that have resistance to Tx
genetically superior
resistance and VL
low VL, resistance less likely
high repliation - resistance more likely to produce mutations that are reisstance
drugs that only require 1/small number of mutations to become resistant
NNRTIs
NRTIs
integrase inhibitors
drugs that need multiple mutaitons for resistance to occur
protease inhibitors
-> better for patient who has bad ahderence
2 reasons for taking HIV drugs with food
- to reduce se eg. ritonavir, zidovudine
- to inc absorption of lipid somuble drugs
types of drug-drug interactions
- absorption
- transporter proteins (intesitinal & hepatic)
- metabolism
- renal clearance
types of absorption interactions with HIV meds
- chelation
- binding prevents absorption
- integrase inhibitors + ions (Ca, Fe supplements) - changes to gastric pH
- reducing absorption
- atazanavir + rilpivirine c/i with PPIs
How can trnasporter proteins cause drug interactions?
drugs can inhibit or induce transporter proteins
intestinal, hepatic, BBB
How can metabolism cause drug interactions?
inhibition OR induction of CYP450 or UGT enzymes
drugs that effect CYP450
PI & NNRTIs
they’re substrates of CYP450, inducers and inhibitors
example of drugs that casue renal inufficiency
PIs and tenofovir
