HIV Flashcards
which HIV group is more virulent
HIV-1
what is the target site for HIV
CD4+ receptors
what is CD4
glycoprotein found on the surface of a range of cells including T helper lymphocytes dendritic cells macrophages microglial cells
what do CD4+ Th lymphocytes do
essential of induction of adaptive immune response
- recognition of MHC2 antigen-presenting cell
- activation of B cells
- activation of cytotoxic T cells
- cytokine release
how does HIV effect the immune response
- sequestration of cells in lymphoid tissue (reduced circulating CD4+ cells)
- reduced proliferation of CD4+ cells
- reduction of CD8+ T cell activation (dysregulated expression of cytokines and increasing susceptibility to viral infections)
- reduction in antibody class switching (reduced affinity of antibodies produced)
chronic immune activation
normal CD4+ Th cell levels
500-1600 cells/mm^3
level of CD4+ cells with risk of opportunistic infections
<200 cells/mm^3
when is HIV replication fastest
very early and very late infection
how often is a new generation of HIV produced
every 6-12 hours
what is the average time to death without treatment
9-11 years
pathogenesis of HIV infection
infection of mucosal CD4 cell (langerhans and dendritic cells)
transport to regional lymph nodes
infection established within 3 days of entry
dissemination of virus
average onset of HIV symptoms
2-4 weeks post infection
primary HIV infection presentation
fever maculopapular rash myalgia pharyngitis headache aseptic meningitis
what occurs during asymptomatic HIV infection (after initial presentation)
ongoing viral replication
ongoing CD4 count depletion
ongoing immune activation
risk of onward transmission if remains undiagnosed
what is an opportunistic infection
an infection caused by a pathogen the does not normally produce disease in a health individual
opportunistic pneumonia
pneumocystis jiroveci
signs/symptoms of pneumocystis pneumonia
insidious one
SOB dry cough
exercise desaturation
treatment of pneumocystis pneumonia
high dose cotrimoxazole (+/- steroid)
types of TB more common in HIV+ individuals
symptomatic primary infection reactivation of latent TB lymphadenopathies miliary TB extrapulmonary TB multi-drug resistant TB immune reconstitution syndrome
presentation of cerebral toxoplasmosis
headache fever focal neurology seizures reduced consciousness raised ICP
presentation of CMV
reduced VA
floaters
abdo pain/diarrhoea/PR bleeding
skin infections associated with HIV
HZV HSV HPV penicilliosis histoplasmosis
presentation of HIV-associated neurocognitive impairment
reduced short-term memory
+/- motor dysfunction
presentation of progressive multifocal leukoencephalopathy
rapidly progressing
focal neurology
confusion
personality change
what is ‘slim’s disease’
HIV-associated wasting
AIDS related cancers
kaposi’s sarcoma (vascular tumour)
non-hodgkins lymphoma
cervical cancer
factors increasing sexual transmission risk
unreceptive sex
trauma
genital ulceration
concurrent STI
forms of parenteral transmission
infection drug use (sharing needles etc)
infected blood products
iatrogenic
how can HIV be transmitted from mother to child
in utero/trans-placental
delivery
breast-feeding
likelihood of an at-risk baby becoming infected
1/4
group most at risk of HIV (UK)
MSM
what percentage of people with HIV are undiagnosed
17%
which group is most likely to be undiagnosed
heterosexual men
who should be tested for HIV
universal testing in high prevalence areas
opt-out in certain clinical settings
screening of high risk groups
testing in the presence of ‘clinical indicators’
high risk groups that should be screened regularly
MSM
females with bisexual male partners
PWIDs
partners of people with HIV
endemic areas
sub-saharan africa
caribbean
thailand
what is needed for a HIV test
venous blood sample for serology
which markers are highest in the first 3 months of infection
viral load
p24 (antigen)
which markers are highest in chronic infection
antibody
which markers are highest in late disease
antibody and viral load
what do HIV antibody tests detect
HIV-1 and HIV-2 antibody
IgM and IgG
which test has a shorter window period
4th generation HIV test
what is the difference between 3rd and 4th generation HIV test
3rd generation - antibody only - window period 20-25 days 4th generation - antibody and antigen - shorter window period (14-28 days)
a negative 4th generation test performed at ___ weeks after exposure is highly likely to exclude HIV infection
4 weeks
what is a rapid HIV test
fingerprick specimen or saliva
results within 20-30 minutes
3rd/4th generation
wide variation in performance
advantages of rapid HIV test
simple to use no lab required no venipuncture required no anxious wait reduce follow up good sensitivity
disadvantages of rapid HIV test
expensive quality control poor positive predictive value in low prevalence settings not suitable for high volume can't be relied on in early infection
which enzyme is used in HIV viral RNA replication
reverse transcriptase
what is the function of integrase
integrates the new viral double stranded DNA into the host DNA
what is the function of protease
cleaves the viral proteins into smaller proteins to form mature HIV particles
what are targets for anti-retroviral drugs
reverse transcriptase integrase protease entry (fusion or CCR5 receptor) maturation
when are protease inhibitors used in HIV treatment
for non-responsive HIV
how do CCR5 receptors work
block the correceptor to prevent virus entering the cell
what is highly active anti-retroviral therapy
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
reduce morbidity and mortality
minimise toxicity
why is there a higher rte of ‘mistakes’ during viral replication than human DNA replication
reverse transcriptase doesn’t have a ‘proof-reading’ ability so can’t tell if it has made a mistake
transcriptase does have this function so can detect mutations
how to prevent drug resistance
adherence/compliance
- lifestyle
- tolerability
- pharmacokinetics
- drug-drug interactions
- treatment interruptions
what is functional mono therapy
if taking combination therapy that is suddenly stopped, the drug with the longest half-life will continue to be present in the blood which therefore puts it at risk of becoming resistant
skin side effects of HAART
rash
hypersensitivity
CNS side effects of HAART
mood
psychosis
renal side effects of HAART
proximal renal tubulopathies
bone side effects of HAART
osteomalacia
CVS side effects of HAART
increased MI risk
haematological side effects of HAART
anaemia
GI side effects of HAART
transaminitis
fulminant hepatitis
how to prevent transmission of HIV from mother to child
HAART during pregnancy vaginal delivery if undetected viral load (at 36 weeks) c-section if detected viral load 4/52 PEP for neonate exclusive formula feeding
eligibility criteria for prep
high risk for HIV (HIV+ partner with detectable viral load or MSM or transwoman)
age >16
HIV negative
willing to stop if criteria no longer apply
resident in scotland
