HIV Flashcards
what type of virus is HIV
retrovirus (When it makes DNA it uses reverse transcriptase rather than dna transcriptase enzyme)
what are the two groups of things AIDs causes
oppurtunistic infections
AIDs related cancers
what does AIDs stand for
acquired immunodeficiency syndrome
what are the two types of HIV
HIV-1 responsible for global pandemic
HIV-2 less virulent, usually limited to west africa
what does HIV target
CD4+ receptoes
what is CD4
glycoprotein found on the surface of a range of cells: T helper lymphocytes dendritic cells macrophages microglial cells
what do CD4+T helper cells do
involved in inducing adaptive immune response recognise MGC2 antigen presenting cell activate B cells activate CD8+ cells cytokine release
(transmit message from antigen presenting cells to effector cells- B and T cells, marcophages)
how does HIV affect the immune response
sequesters cells in lymphoid tissue and reduced proliferation of CD4+= reduced CD4+ cells
reduction of CD8+ (cytotoxic) T cell activation = dysregulates cytokine expression, increased susceptibility to viral infections
reduction in antibody class switching= reduces affinity of antibodies produced
chronic immune activation (microbial translocation)
combined makes patient more susceptible to viral, fungal, mycobacterial infections and infection induced cancers
what is a normal CD4+Th cell count
500-1600 cells/mm3
what CD4+T count poses a risk for opportunistic infections
<200
when is there rapid HIV viral replication
in early and very late infection
new generation every 6-12 hours
what happens to viral load as antibodies start to form
goes down
CD4 count rises in asymptomatic infection, does it ever go back to normal
no, gets lower as disease progresses
what is the path of HIV infection
mucosal CD4 cells (langerhans and dendritics cells) usually rectal, vaginal or cervical
transport to regional lymph nodes
infection established within 3 days of entry
dissemination of virus
when are the onset of symptoms in primary infection
2-4 weeks after infection
what are the symptoms of primary infection
combo of fever rash (maculopapular) myalgia pharyngitis headache/ aseptic meningitis (can infect microglial cells as primary infection)
flu/ glandular like illness
is there risk of transmission during primary infection
yes- very high
what is happening during asymptomatic HIV infection
ongoing:
- viral replication
- CD4 count depletion
- immune activation
risk of transmission
does HIV become latent
no, as not sleeping during asymptomatic infection and immune system not back to normal
what type of lesions on MRI in toxoplasmosa
ring enhanced lesions in brain
what causes penumocystis pneumonia
IN EXAM
pneumocystis jiroveci
what CD4 threshold predisposes you to pneumocystis pneumonia
(IN EXAM)
<200
what are the symptoms of pneumocystis pneumonia
IN EXAM
insidious onset
SOB
dry cough
may have low grade fever
what are the signs of pneumocystis pneumonia
IN EXAM
exercise desaturation CXR: -may be normal -interstitial infiltrates -reticulonodular markings
how do you diagnose pneumocystis pneumonia
IN EXAM
BAL (bronchoalveolar lavage - bronchoscopeis passed through the mouth or nose into thelungsand fluid is squirted into a small part of the lung and then collected for examination)
and immunofluorescence +/- PCR
what is the treatment for pneumocystis pneumonia
IN EXAM
high dose co-trimoxazole +/- steroid
what is the prophylaxis for pneumocystis pneumonia
IN EXAM
low dose co-trimoxazole
what should you be aware of in TB and HIV
drug- drug interactions
what forms of TB infection are more common in HIV+ve patients
symptomatic primary infection reactivation of latent TB lymphadenopathies miliary TB extrapulmonary TB multi drug resistant TB immune reconstitution syndrome
what causes cerebral toxoplasmosis
toxoplasma gondii
what is the pathology of cerebral toxoplasmosis
reactivation of latent infection- causes multiple cerebral abscess (chorioretinitis)
what are the symptoms/ signs of cerebral toxoplasmosis
heachache fever focal neurology (as focal abscesses) seizures reduced consciousness raised ICP
what CD4 threshold puts you at risk for cerebral toxoplasmosis
<150
what screen (not HIV) does everyone with a CD4 count <50 get
ophthalmic (looking for CMV)
what CD4 threshold puts you at risk for cytomegalovirus
<50
what is the pathology of CMV
reactivation of latent virus causes retinitis, colitis and oesophagitis
what is the presentation of CMV
reduced visual acuity- can cause blindness floaters abdo pain diarrhoea PR bleeding
what skin infections are seen in HIV
herpes zoster:
- multidermatomal
- recurrent
herpes simplex:
- extensive
- hypertrophic (can form wart/ tumour like mass)
- aciclovir resistant
HPV:
- extensive
- recalcitrant
- dysplastic
- women with HIV have annual cervical screening
penicilliosis
histoplasmosis
what organisms causes HIV associated neurocognitive impairment
HIV-1
what CD4 count purs you at risk of HIV associated neurocognitive impairment
any
increased incidence with increased immunosuppression though
what is the presentation of HIV associated neurocognitive impairment
reduced short term memory +/- motor dysfunction
what organisms causes progressive multifocal leukoencephalopathy
JC virus (reactivation of latent virus)
what CD4 count puts you at risk of progressive multifocal leukoencephalopathy
<100
what is the presentation of progressive multifocal leukoencephalopathy
rapidly progressing
focal neurology
confusion
personality change
what is the pathology of progressive multifocal leukoencephalopathy
progressive white matter change, multifocal
what are neurological presentation of HIV
HIV associated neurocognitive impairment progressive multifocal leukoencephalopathy distal sensory polyneuropathy mononeuritis mulitplex vacuolar myelopathy aseptic meningitis guillan barre syndrome viral meningitis (CMV, HSV) cryptococcal meningitis neurosyphilis
what causes HIV associated wasting
metabolic (chronic immune activation)
anorexia (multifactoral inc psychological)
malabsorption/ diarrhoea
hypogonadism
what are the AIDs related cancers
kaposi’s sarcoma
non hodgkins lymphoma
cervical cancer
what organism causes karposis sarcoma
human herpes virus 8
what type of tumour is karposis sarcoma
vascular tumour
what CD4 count puts you at risk of karposis sarcoma
any
increased incidence with increase immunosuppression though
where can you get karposis sarcoma
cutaneous
mucosal
visceral (pulmonary, GI)
what is the treatment for karposis sarcoma
HAART
local therapies
systemic chemotherapy
what organism causes non hodgkins lymphoma in AIDs
EBV (burkitts lymphoma, primary CNS lymphoma)
what is the presentation of non hodgkins lymphoma in AIDs
more advanced B symptoms (systemic symptoms in both hodgkins and non hodgkins lymphoma- fever, night sweats, weight loss) bone marrow involvement extranodal disease increased CNS involvement
is the diagnosis and treatment any different for non hodgkins lymphoma in AIDs
diagnosis same
treatment add HAART
what organism causes cervical cancer
HPV
why is HPV more likely to cause cervical cancer in AIDs
persistence of HPV infection
rapid progression to severe dysplasias and invasive disease
what can HPV in AIDs cause
recalcitrant warts
high grade cervical, vulval, anal, penil intraepithelial neoplasia
what are the non opportunistic infection symptoms of HIV
mucosal candidiasis seborrhoeic dermatitis (eczema and fungal infection) diarrhoea fatigue worsening psoriasis lymphadenopathy parotitis epidemiologically linked conditions: STIs, hep B and C
is mucosal candidiasis an OI
no
is seborrhoeic dermatitis an OI
no
why does psoriasis get worse in HIV
as is CD8 mediated- when CD4 goes down these go up
both go down in AIDs
what are the possible haematological manifestations of HIV
anaemia (up to 90% affected)
thrombocytopenia (ITP) (CD4 300-600)
what causes the haematological manifestations of HIV
HIV itself
opportunistic infections
AIDs malignancies
(HIV drugs)
what CD4 can you get haematological manifestations
any
higher incidence with higher immunosuppression
what is the most common mode of HIV transmission
sexual transmission (95%)
- sex between men (53%)
- sex between men and women (42%)
what increases the risk of sexual transmission of HIV
anoreceptive sex (lots of CD4, only 1 cell thick- more susceptible to trauma)
trauma
genital ulceration
concurrent STI
what are the ways in which HIV is transmitted parenterally
injection drug use (2%)
infected blood products
iatrogenic
via what ways can a mother transmit HIV to her child
in utero/ trans-placental
delivery
breast feeding
how many at risk babies get infected
1 in 4
what is the risk of mother to child transmission when viral load undetected at delivery
0.1%
what percentage of people living with HIV in UK are undiagnosed
7%
~7500
who are the high risk groups for HIV
highest risk= MSM (1 in 17/ 1 in 7 in london)
heterosexuals (aged 15-44, 1:1000. black african men 1:25, black african women 1:23)
PWID (aged 15-44, 1:263)
what group of people are most likely to be diagnosed late
heterosexual men
who should be tested for HIV
universal testing in high prevalence areas (>0,2%) (all general medical admissions, all new patients registering at general practice)
some places have opt out testing (TOP services, GUM clinics, drug dependency services - higher prevalence in these populations. antenatal services and assisted conception services- risk of undiagnosed HIV in these settings unacceptable)
screening of high risk groups
when clinical indicators
what high risk groups are screened for HIV
MSM female partners of bisexual men people who inject drugs partners of people living with HIV adults/children from endemic areas children born to HIV+ or untested mothers from endemic areas sexual partners from endemic areas history of iatrogenic exposure in an endemic area
what are the endemic areas for HIV
sub saharan africa
caribbean
thailand (south east asia)
rising epidemics in russia and eastern europe
what do you need to do to gain consent for a HIV test
Explain to patient they are being offered an HIV test and why
- normalise
What the benefits of testing are
- Improve long term health
- Protect partner(s)
How and when they can expect to receive results
Reassure re: confidentiality
Written information can be made available (different languages)
is it venous or arterial blood for serology in HIV test
venous
what do you do for HIV testing if patient incapacitated
only test if in their best interest
consent from relative not required
if safe wait till patient regains capacity
get support from HIV team if required
what markers of HIV are used to detect infection
viral RNA (viral genome) capsule protein (P24) (antigen) antibodies
how long till seroconversion (formation of antibodies)
3 months
what does seroconversion mark
the end of primary infection, start of chronic infection
what happens to P24 (antigen) as HIV progresses
high in primary infection, goes down during chronic infection, rises again in late disease
what happens to viral load as HIV progresses
high initial infection
what do 3rd gen HIV tests look for
HIV 1 and 2 antibody
detect IgM and IgG
very sensitive/ sepcific in established infection
window period of 20-25 days
what do 4th gen HIV tests look for
combines antibody and antigen
shortens window period to 14-28 days
what does a negative 4th gen HIV test mean
highly likely to exclude HIV infection
how do rapid HIV tests work
finger prick blood or saliva
results in 20-30 mins
can be 3rd or 4th gen
what are the downsides of rapid HIV tests
Expensive ~£10
Poor positive predictive value in low prevalence settings
Not suitable for high volume
what does undiagnosed HIV cause
Late diagnosis
Morbidity/mortality
Onward transmission
what CD4 count do you give PCP prophylaxis
<200
do you always do RNA sequencing in HIV infection
yes always to find out which type it is
type B most common in MSM and PWID
what else do you screen for in HIV infection depending on where a patient has traveled
TD and schistosomiasis
what else should you test for in MSM
LGV
describe the life cycle of HIV
binding to CD4 molecules and coreceptors (CCR5 and CXCR4)
virus fuses with the cell
virus penetrates and empties its contents into cell
reverse transcriptase converts single stranded viral RNA into double stranded DNA
intergrase combines viral DNA with cells own
transcription of viral DNA when host cell divides
sets of viral protein chains come together
budding- immature virus pushes out of the cell taking some of the membrane with it
protease starts processing the proteins in newly forming virus
immature virus breaks free from infected cell protease enzyme finishes cutting HIV protein chains into individual proteins that combine to make a new working virus
what can anti retoviral drugs target
reverse transcriptase (NRTI and NNRTI) integrase protease entry into cell: fusion and CCR5 receptors
what is highly active anti
THIS IS IN EXAM
a combination of 3 drugs from at least 2 drug classes to which the virus is susceptible
what is the purpose of HAART
reduce viral load to undetectable
restore immunocompetence (allows immune system to recover)
reduce morbidity and mortality
how do you prevent HIV drug resistance
ADHERENCE lifestyle tolerability pharmacokinetics drug-drug interactions treatment interuptions (virus becomes restistence when in monotherapy, when break in treatment drug with longest half life will become monotherapy)
what do you do if a patient isnt going to be able to take medication for a while
stop therapy before break and give protease therapy- hard to get resistance to
allowing some viral breakthroughs is better than resistance
what is an ARV
anti retro viral
what are the common HAART toxicities
gi side effects: protease inhibitors, (transaminitis, fulminant hepatitis- nevirapine)
skin:rash, hypersensitivity, SJS (abacavir, nevirapine)
CNS: mood, psychosis (efavirenz)
renal toxicity: proximal renal tubulopathies (tenofovir, atazanavir)
bone: osteomalacia (tenofovir)
CVS: increased MI risk (abacavir, lopinavir, maraviroc)
haematology: anaemia (zidovudine)
how do protease inhibitors affect liver enzymes
protease inhibitors are potent liver enzyme inhibitors= they may increase the bioavailability of other drugs which are metabolised by those enzymes
they may decrease the bioavailability of drugs which require metabolism for their activation
how do NNRTIs affect liver enzymes
are potent liver enzyme inducers:
they may decrease the bioavailability of other drugs which are metabolised by those enzymes
they may increase the bioavailability of drugs which require metabolism for their activation
what are common co infections with HIV that affect treatment options
hep C and TB
hep B and HIV have same treatment
what do a lot of women with HIV get
early menopause- osteoporosis
what preventative medicine can be done in HIV treatment
exercise smoking cessation (CVS risk) STI screening hep A/B vaccine flu vaccine HPV vaccine harm reduction- needle exchange, condoms etc
how can HIV affect psychosocial well being
Adjustment to diagnosis
Confusion, guilt (+ survivor guilt), blame
Impact of HIV on health
Concerns about future
Feelings of isolation
Relationships
Spiritual
is partner notification and disclosure mandatory
no, is a voluntary process
what are the different strategies to partner notification and disclosure
partner referral (partner tells them) provider referral (HCP contacts partners, is anonymous) conditional referral (if HPC doesnt hear from partner by a certain time will contact them)
when does a doctor have a duty of care to a patients partner
when they are a known third party
what are the barrier to partner notification and disclosure
fear:
-rejection
-isolation
-violence
confidentiality
stigma
what is stigma
the shame/ disgrace attached to something regarded as socially unacceptable
how does stigma in HIV manifest
discrimination and ostracisim
how is the sexual transmission of HIV prevented
condom use
HIV treatment
STI screening and treatment
sero-adaptive sexual behaviours (more likely to pass it on in MSM if insertive partner)
disclosure (more accepting of condoms)
post exposure prophylaxis (up to 72 hours after, taken for 4 weeks)
pre exposure prophylaxis (taken every day/ event based dosing)
can you pass on HIV when viral load is <200
no
what are the conception options for sero-discordant couples
for all:
- treatment as prevention
- +/- timed condomless sex
- ?HIV PrEP for partner
HIV + female, -male:
-?self insemination
does adding PrEP when undetectable reduce risk of transmission
no as risk already 0
how can you prevent mother to child transmission
HAART during pregnancy - SVD if undetectable, caearean if detectable
- 4/52 PEP for neonate (give AVR to baby for up to 4 weeks after birth)
- exclusive formula feeding
how does having other STIs affect risk of HIV
increases risk of both getting it and passing it on
what prevention strategies have helped reduce HIV transmission
needle exchange STI testing and treatment condom programmes PEP and PrEP circumcision (epithelium on glans becomes keratinised, reduced chance of acquiring HIV) treatment as prevention behavioural change interventions
where in UK is PrEP licensed
just scotland
what is the PrEP eligibility criteria
is patient high risk?:
- HIV + partner with detectable viral load (>50)
- MSM/ transwoman (unprotected anal intercourse in 12/12 and likely to do so again in next 3/12 or confirmes bacterial rectal STI in last 12/12)
- other high risk factor
is patient eligible?:
- age >/= 16
- HIV negative
- can commit to 3/12ly follow up
- willing to stop if eligibility criteria no longer apply
- resident in scotland
does PrEP work
reduces incidence by 86%
