HIV Flashcards
What is HIV?
A retrovirus
What is AIDs?
Syndrome caused by HIV
Opportunistic infections
AIDs related cancers
Is AIDs preventable?
Yes; by early HIV diagnosis and treatment
Is HIV preventable?
Yes; there is pre and post exposure prophylaxis
What are the 2 different types of HIV?
HIV-2; originated in west africa (known as simian immunodeficiency virus). Noone in Tayside with HIV-2
HIV-1; originated in Central/West African Chimps
HIV-1 group M was responsible for the global pandemic in 1981
What immune cells does HIV target?
CD4+ receptors
What are CD4?
Glycoprotein found on the surface of cells including: T helper lymphocytes Dendritic cells Macrophages Microglial cells
What is the purpose of CD4+ T helper cells?
Induction of adaptive immune response Recognition of MHC 2 antigen presenting cells Activation of B cells Activation of CD8+ T cells Cytokine release
What are those with HIV infection susceptible to?
Viral infections
Fungal infections
Mycobacterial infection
Infection-induced cancers
What effect does HIV infection have on the immune response?
Sequestration of cell in lymphoid tissue (reduced CD4+ T cells circulating)
Reduced proliferation of CD4+ T cells
Reduction in CD8+ T cells (dysregulated expression of cytokines, increasing susceptibility to viral infections)
Reduction in antibody class switching
Chronic immune activation
What is a normal CD4+ T count?
500-1600 cells/mm3
What CD4 count correlates with a risk of opportunistic infections?
<200
When is HIV viral replication at its highest?
Very early and very late infection
New generation every 6-12 hours
When will viral load tend to peak (coincides with lowest CD4 count)?
6 weeks
How will HIV spread?
Infection of mucosal CD4 cells (langerhans anc dendritic cells)
Transport to regional lymph nodes
Infection established within 3 days of entry
Dissemination of virus
Why is the 72 hour period crucial in the early stages of HIV?
You can give post exposure prophylaxis in this time period to prevent HIV progressing
When will symptoms tend to present after infection?
2-4weeks
What are the symptoms of HIV infection?
Fever Rash (maculopapular) Myalgia Pharyngitis Headache/ aseptic meningitis
What is going on in asymptomatic HIV infection?
Ongoing viral replication
Ongoing CD4 count
Ongoing immune activation
Risk of onward transmission if remains undiagnosed
What is an opportunistic infection?
An infection caused by a pathogen that does not normally produce disease in a healthy individual
It uses the “opportunity” afforded by a weakened immune system to cause disease
What organism causes pneumocystis pneumonia?
Pneumocystis Jiroveci
What is the CD4 threshold for pneumocystis pneumonia?
<200
What are the symptoms and signs of pneumocystis pneumonia?
Insidious onset
SOB
Dry cough
Exercise desaturation
What can be seen on CXR with pneumocystis pneumonia?
Normal
Interstitial infiltrates
reticulonodular markings
How is pneumocystis pneumonia diagnosed?
BAL and immunofluorescence
+/- PCR
What is the treatment of pneumocystis pneumonia?
High dose co-trimoxazole +/- steroid
Is prophylaxis given for pneumocystis pneumonia?
Yes; if CD4 count <200 start low dose co-trimoxazole
In terms of TB and HIV, what is more common in HIV+ individuals?
Symptomatic primary infection Reactivation of latent TB Lymphadenopathies Miliary TB Extrapulmonary TB Multi-drug resistant TB Immune reconstitution syndrome
What is the issue with HIV with concurrent TB?
Drug-drug interactions between antiretrovirals and TB drugs
Which organism causes cerebral toxoplasmosis?
Toxoplasma gondii
What is the CD4 threshold for cerebral toxoplasmosis?
<150
What can cerebral toxoplasmosis cause?
Reactivation of latent infection
Multiple cerebal abscess - chorioretinitis
What are the sy/si of cerebral toxoplasmosis?
Headache Fever Focal neurology Seizures Reduced conciousness Raised ICP
What is the CD4 threshold for CMV?
<50
What can CMV cause?
Retinitis
Colitis
Oesophagitis
What is the presentation of CMV?
Reduced visual acuity Floaters Abdo pain Diarrhoea PR bleeding
What is the guidelines surrounding ophthalmic screening in HIV?
All individuals with a CD4 <50 should receive ophthalmic screening
How will herpes zoster present in HIV +ve patients?
Multidermatomal
Recurrent
How will herpes simplex present in HIV +ve patients?
Extensive
Hypertrophic
Aciclovir resistant
How will HPV present in HIV +ve patients?
Extensive
Recalcitrant
Dysplasitc
What organism causes HIV assoc neurocognitive impairment?
HIV-1
What is the CD4 threshold for HIV assoc neurocognitive impairment?
Any
Increased incidence with increased immunosuppression
What is the presentation of HIV assoc neurocognitive impairment?
Reduced short term memory
Motor dysfunction
What organism causes Progressive Multifocal Leukoencephalopathy (PML)?
JC virus
What is the CD4 threshold for PML?
<100
What is the presentation of PML?
Rapidly progressing
Focal neurology
Confusion
Personality changes
What are common opportunistic infections seen in HIV?
Pneumocystis pneumonia TB Cerebral toxoplasmosis CMV Herpes zoster Herpes simplex HPV PML
Apart from HIV assoc neurocognitive impairment and PML how can HIV present neurologically?
Distal sensory polyneuropathy Mononeuritis multiplex Vacuolar myelopathy Aseptic meningitis GBS Viral meningitis (CMV, HSV) Cryptococcal meningitis Neurosyphilis
What is the aetiology behind HIV assoc wasting?
Metabolic (chronic immune activation) Anorexia (multifactorial) Malabsorption Diarrhoea Hypogonadism
What causes Kaposi’s Sarcoma?
HHV 8
What is the pathogenesis of kaposi’s sarcoma?
Vascular tumour
What is the CD4 threshold for kaposi’s sarcoma?
Any
Increased incidence with increased immunosuppression
What is the presentation of kaposi’s sarcoma?
Cutaneous
Mucosal
Visceral; pulmonary, GI
What is the treatment of Kaposi’s Sarcoma?
HAART
Local therapies
Systemic chemo if visceral
What virus causes non-hodgkin’s lymphoma in HIV +ve patients?
EBV (also assoc with burkitt’s lymphoma and primary CNS lymphoma)
What is the presentation of non-hodgkin’s lymphoma?
More advanced B symptoms Bone marrow involvement Extranodal disease Increased CNS involvement
What is the CD4 threshold for non-hodgkin’s lymphoma?
Increased incidence with increased immunosuppression
What organism causes cervical cancer in HIV?
HPV
Persistence of HPV infection
Rapid progression to severe dysplasia and invasive disease
Who should HIV testing be offered to in terms of cervical dysplasia?
HPV disease
Recalcitrant warts
High grade; CIN, VIN, AIN, PIN
What symptoms are generally present in the “asymptomatic” period of HIV?
Mucosal candidiasis Seborrhoeic dermatitis Diarrhoea Fatigue Worsening psoriasis Lymphadenopathy Parotitis Epidemiologically linked conditions; STIs, hep B, hep C
What are the haematological manifestations of HIV?
Anaemia (up to 90%)
Thrombocytopenia (ITP)
What are the AIDs related cancers?
Kaposi’s sarcoma
Non-hodgkin’s lymphoma
Cervical cancer; VIN, CIN2 or higher
What is the main mode of HIV transmission?
Sexual; 95%
53% in MSM
42% men and women
What are factors that increase the transmission risk of HIV sexually?
Anoreceptive sex
Trauma
Genital ulceration
Concurrent STI
How can HIV be transmitted parenterally?
PWID
Infected blood products
Iatrogenic
How can HIV be passed from mother to child?
In utero/ trans placental Delivery Breast feeding 1 in 4 at risk babies become infected 1 in 3 HIV+ infants will die before first birthday
What is the total number of people living with HIV in the UK?
104,000
Prevalence is 1.6/1000
7% undiagnosed
Which group is highest risk for HIV in the UK?
MSM
Who should be tested for HIV?
Universal testing in high prevalence areas
Opt-out testing in certain clinical settings
Screening in high risk groups
Testing in the presence of clinical indicaors
What is universal testing for HIV?
In high prevalence areas in the UK (>0.2%), HIV testing is recommended to all general medical admissions and all new patients registering at GP
Which services are involved in out-out HIV testing?
Termination of pregnancy services GUM clinics Drug dependence services Antenatal services Assisted conception services
Which high risk groups are screened for HIV?
MSM Female partners of bisexual men PWID Partners of people living with HIV Adults from endemic areas Children from endemic areas Sexual partners from endemic areas History of iatrogenic exposure in endemic area
What are high prevalence areas for HIV?
Sub-saharan africa
Caribbean
Thailand
When should HIV testing be performed under clinical grounds?
When HIV falls within the DD, a HIV test should be performed regardless of risk factors
How can consent be obtained for a HIV test?
Explain to patient they are being offered a HIV and why
Benefits of testing; improve long term health, protect partner(s)
How and when receive results
Reassure re: confidentiality
How is a HIV test taken?
Document consent or refusal
Obtain venous sample for serology
Request via ICE
Ensure pathway in place for retrieving and communicating result
If incapacitated: only take if in patients best interest, consent from relative not required, if safe wait until patient regains capacity
What marker of HIV is used by labs to detect infection?
Antibodies take 3 months
So we now look for p24 markers
What is a 3rd generation HIV test?
HIV1 and HIV2 antibodies; detects IgG and IGM
Very sensitive/ specific in established infections
Window period; 20-25 days
What is a 4th generation HIV test?
Combined antibody and antigen (p24)
Shortens window period
Window period; 14-28 days
Describe a 4th generation test and a window period?
A negative 4th generation test performed at 4 weeks following an exposure is highly likely to exclude HIV infection
What is a rapid HIV test?
Finger Prick blood specimen or saliva
Results within 20-30 mins
3rd gen (Ab only) or 4th gen (Ab/Ag)
Advantages of rapid HIV test?
Simple No lab No venipuncture No anxious wait Reduce follow up Good sensitivity
Disadvantages of rapid HIV test?
Expensive Quality control Poor predictive value in low prevalence settings Not suitable for high volume Not so reliable in early infection
What should you do when someone first presents with HIV?
Staging infection Opportunistic infections OI prophylaxis Psychological/ emotional support Education HIV treatment Mode of acquisition STI screening Partner notification Prevention medicine/ vaccinations Prevention of onward transmission
What should be sent in someone with HIV who tests positive for rectal chlamydia?
LGV serology
What conditions commonly co-exist with HIV?
Hep b/c Syphilis STI Schistosomiasis TB
What are the targets for antiretroviral drugs?
Reverse transcriptase Integrase Protease Entry; fusion and CCR5 receptor Maturation
What is HAART - exam q?
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
Describe the HIV replication cycle?``
1: fusion of HIV to the host cell surface
2: HIV RNA , reverse transcriptase, integrase and other viral proteins enter the host cell
3: Viral DNA is formed by reverse transcriptase
4: viral DNA is transported across the nucleus and integrates into the host DNA
New viral RNA is used as genomic RNA and to make viral proteins
6: new viral RNA and proteins move to cell surface, and a new, immature HIV forms
7: virus is released. Viral protease cleaves new polyproteins to create mature infectious virus
What are the 7 HIV drug classes?
Non-nucleoside reverse transcriptase inhibitors
Nucleoside reverse transcriptase inhibitors
Protease inhibitors
Fusion inhibitors
CCR5 antagonists
Integrase strand transfer inhibitors
Post-attachment inhibitors
What is the mode of action of NNRTIs and NRTIs?
Block conversion of HIV RNA to HIV DNA
What is the mode of action of protease inhi1bitors?
Block protease which prevents new HIV from becoming mature and therefore able to infect other CD4 cells
What makes up truvada?
Emtricitabine
Tenofovir
Both NRTIs
What is truvada used for?
PrEP
What is a common single tablet co-formulation used in HIV?
Tenofovir (NRTI)
Emtricitabine (NRTI)
Efavirenz (NNTRI)
What adhernace is required to prevent resistance in HIV?
95%
What helps to prevent HIV resistance?
Adherence Lifestyle Tolerability Pharmacokinetics Drug-drug interaction Treatment interruptions
What would make the perfect ARV?
Tolerability Low toxicity Low pill burden Low dosing frequency Minimal drug-interactions High barrier to resistance
What are the GI side effects of HAART (commonly protease inhibitors)?
Transaminitis
Fulminant hepatitis
What are common skin side effects of HAART (abacavir, nevirapine)?
Rash
Hypersensitivity
SJS
What are common CNS side effects of HAART (efavirenz)?
Mood - suicidal ideation n
Psychosis
Insomina
What are common renal side effects of HAART (tenofovir, atazanavir)?
Proximal renal tublopathies
What are common bone side effects of HAART (tenofovir)?
Osteomalacia
What are common CVS side effects of HAART (abacavir, lopinavir, maraviroc)?
Increased MI risk
What are common haematological side effects of HAART (zidovudine)?
Anaemia
Majority of people with HIV have anaemia be that due to HIV itself or the drug
Describe the effect of HAART on liver enzymes?
Protease inhibitors are potent liver enzyme inhibitors
NNRTIs are potent liver enzyme inducers
Some drugs require pharma boosting with potent liver enzyme inhibitors
What is the issue with hep C and TB co-infections?
Drug interactions with hepatitis and TB treatment
What vaccines are given to those with HIV?
Hep A/B
Flu
Pneumococcus
HPV
Is partner notification voluntary?
Yes
What are the different methods of partner notification?
Partner referral
Provider referral
Conditional referral
What are barriers to PN and disclosure?
Fear; rejection, isolation, violence
Confidentiality
Stigma
How does stigma manifest?
Discrimination
Ostracism
How can onward HIV transmission be prevented?
Condom use HIV treatment STI screening and treatment Sero-adaptive sexual behaviours; risk of transmission lower when receptive anal sex in MSM Disclosure PEP PrEP
When can PEP be taken?
72 hours after expsoure
What is the guidelines surrounding reproduction with HIV positive male or females?
Treatment as prevention; if either partner has an undetectable viral load then it CANNOT be transmitted…adding PrEP will make no difference
How can mother to child transmission of HIV be prevented?
HAART during pregnnacy Vaginal delivery if undetected viral load C section if detected viral load 4/52 PEP for neonate Exclusive formula feeding
When is viral load measured in pregnant women to help determine vaginal or c section?
36 weeks
What is the risk of MTCT is viral load undetectable at birth?
<0.1% risk
What are the HIV prevention strategies?
Needle exchange Testing and treatment for STIs Condom programmes PEPSE Circumcision PrEP Treatment as prevention
What is the UN AIDs target for 2020?
90-90-90
90% aware of HIV status
90% on HIV treatment
90% virally suppressed
What is the risk reduction of HIV transmission when PrEP is used?
86% efficacy
What is the PrEP eligibility criteria?
High risk for HIV; HIV+ partner with detectable viral load OR MSM who have UPAI > 2 partner in 12/12 and likely to do so again in next 3/12 OR confirmed bacterial rectal STI in last 12/12
Patient eligibility:
Aged >16 AND can commit to 3/12’ly follow up AND willing to stop is eligibility criteria no longer apply AND resident in Scotland
