Human immunodeficiency virus (HIV) Flashcards
Describe the virology of HIV
RNA retrovirus
2 types (HIV-1 and HIV-2)
Replicated very early or very late in infection
New generation every 6-12 hours
No proof-reading to mutations retained
How does HIV replicate
Surface antigens bind to CD4 receptors and CCRS co-receptors on host cell surface
RNA forms DNA via reverse transcriptase
DNA integrated into host genome
DNA codes for viral proteins which exocytose from cell to form a mature virion
Which HIV strain is responsible for the global epidemic
HIV-1 group M
What are the 2 main surface antigens on HIV
- GP120
- GP41
How is HIV introduced to the body
Infection of mucosal CD4+ cells (Langerhans and dendritic cells)
Then transported to regional lymph nodes, where infection established within 3 weeks
Disseminated around the body
What cells have the CD4 glycoprotein on their surface
- T-helper cells
- Dendritic cells
- Macrophages
- Microglial cells
What are some roles of Th cells
- Recognition of MHCII APCs
- Activation of B cells
- Activation of cytotoxic T-cells (CD8+)
- Cytokine release
What are some effects of HIV on the immune system?
- Reduced circulating CD4+ cells
- Reduced CD4+ proliferation
- Reduced CD8+ T-cell activation and dysregulated cytokine expression
- Reduced antibody class switching and lower affinity antibody production
- Chronic immune activation
What are the main complications of weakened immune system in HIV
Increased susceptibility to viral, fungal, parasitic, mycobacterial infections and infection-induced cancers
Normal CD4+ T-helper cell levels
500-1600 cells/mm3
What CD4+ T-helper cell level carried the highest risk of opportunistic infection
<200cells/mm3
What is the average time from primary infection to death without treatment for HIV
9-11 years
How quickly do symptoms occur in primary HIV infection
2-4 weeks after infection
Presentation of primary HIV infection
- fever
- Rash (Maculopapular)
- Myalgia
- Pharyngitis
- Headache/Aseptic meningitis
What is occurring during asymptomatic HIV infection
Ongoing viral replication
Ongoing CD4 count depletion
Ongoing immune activation
Risk of onwards transmission
What does AIDS stand for
Acquired ImmunoDeficiency syndrome
What is AIDS
The condition of opportunistic infections of cancers in HIV
What is an opportunistic infection
An infection caused by a pathogen that does not normally produce disease in a healthy individual
Common bacteria in AIDS
- Mycobacterial tuberculosis
- Recurrent pneumonia
Common viruses in AIDS
- HSV
- Cytomegalovirus retinitis
- PML
Common parasites in AIDS
- Cerebral toxoplasmosis
- Reactivation of American trypanosomiasis
Common fungi in AIDS
- Pneumocystis jiroveci pneumonia
- Candidiasis of oesophagus or bronchi
- Histoplasmosis
What is PCP?
PneumoCystis Pneumonia
What is the causative organism in PCP
Pneumocystis jiroveci
CD4+ Th threshold for PCP
<200
Symptoms of PCP
Insidious onset
SOB
Dry cough
Signs of PCP
Exercise oxygen desaturation
CXR findings in PCP
- May be normal
- Interstitial infiltrates
- Reticulonodular markings
Diagnosis of PCPO
BAL + Immunofluorescence ± PCR
Management of PCP
High dose co-trimoxazole ± Steroids
Prophylaxis of PCP
Low dose co-trimoxazole
What are some common TB syndromes in AIDS
- Symptomatic primary infection
- Reactivation of latent TB
- Lymphadenopathies
- Miliary TB
- Extra-pulmonary TB
- Multi-drug resistant TB
- immune reconstitution syndrome
What is the causative organism of cerebral toxoplasmosis
Toxoplasmosis gondii
CD4 Th threshold for cerebral toxoplasmosis
<150
How does cerebral toxoplasmosis cause problems in AIDS
Reactivation of latent infection causing:
- Multiple cerebral abscess
- Chorioretinitis
CD4+ Th threshold for CMV in AIDS
<50
Presentation of reactivated CMV in AIDS
- Reduced visual acuity
- Floaters
- Abdominal pain, diarrhoea, PR bleeding
Presentation of reactivated cerebral toxoplasmosis in AIDS
- Headache
- Fever
- Focal neurology
- Seizures
- Reduced consciousness
- Raised ICP
How does CMV cause problems in AIDS
Reactivation of latent infection causing:
- Retinitis
- Colitis
- Oesophagitis
What is offered to all HIV patients with a CD4 level <50
Ophthalmic screening for CMV retinitis
What is HIV-associated neurocognitive impairment
Reduced short term memory and motor dysfunction caused by HIV-1 infection of microglial cells of the brain
What organism causes PML?
Reactivation of JC virus
What does PML stand for in AIDS
Progressive Multifocal Leukoencephalopathy
What is the CD4 threshold for PML
<100
Presentation of PML in AIDS
- Rapidly progressing
- Focal neuropathy
- Confusion
- Personality change
What are some skin infections that can occur in AIDS
Herpes Zoster
Herpes Simplex
Human Papilloma virus
Characteristics of Herpes Zoster in AIDS
Multi-dermatomal
Recurrent
Characteristics of Herpes Simplex in AIDS
- Extensive
- Hypertrophic
- Aciclovir resistant
Characteristics of HPV in AIDS
- Extensive
- Recalcitrant
- Dysplastic
What is HIV-associated wasting (Slim’s disease)
Involuntary weight loss exceeding 10% of baseline body weight, along with diarrhoea or weakness and fever lasting over 30 days.
Causes of HIV-associated wasting
- Metabolic (Energy usage by chronic immune activation)
- Anorexia
- Malabsorption/diarrhoea
- Hypogonadism
What are some examples of HIV-related cancers in AIDS
Kaposi’s sarcoma
Non-Hodgkin lymphoma
Cervical cancer
What organism causes Kaposi’s sarcoma in AIDS
Human Herpes Virus 8
Pathology of Kaposi’s sarcoma
Vascular tumour
Locations of Kaposi’s sarcoma
- Cutaneous
- Mucosal
- Visceral (Pulmonary, GI)
Treatment of Kaposi’s sarcoma
- Anti-retrovirals
- Local therapies
- Systemic chemotherapy
Organism responsible for Non-Hodgkin’s lymphoma in AIDS
EBV
Presentation of Non-Hodgkin’s lymphoma in AIDS
- More advacnes
- B symptoms
- Bone marrow involvement
- Extra-nodal disease
- Increased CNS involvement
What are some non-AIDS symptoms of HIV
- Mucosal candidiasis
- Seborrhoeic dermatitis
- Diarrhoea
- Fatuigue
- Worsening psoriasis
- Lymphadenopathy
- Parotitis
What are some epidemiologically linked conditions with HIV
STIs
Hepatitis B and C
What are some neurological presentations of HIV
- Distal sensory polyneuropathy
- Mononeuritis multiplex
- Vacuolar myelopathy
- Aseptic meningitis
- Guillain-Barre syndrome
- Viral meningitis
- Cryptococcal meningitis
- Neurosyphilis
What causes haematological complications of HIV
- HIV itself
- Opportunistic infections
- AIDS-malignancies
What are some forms of haematological presentations of HIV
Leukopenias
Lymphopenias
Thrombocytopenia (HIV infects megakaryocytes)
What are the 3 main modes of HIV transmission
Sexual (92% UK)
Parenteral transmission
Mother-to-child
What are some ways in which HIV is NOT spread (Common myths)
Oral sex
Biting
Kissing
Contact with eyes
What are some factors which increase risk of HIV transmission during sex?
- Anoreceptive sex
- Trauma
- Genital ulceration
- Concurrent STI
Is MSM or MSW more common in causing HIV spread in the UK
Sex between men and women (39.8% new cases)
(MSM 30%)
What are some forms of parenteral HIV transmission
Injection drug use
Infected blood products
Iatrogenic
What are some ways in which HIV can be spread from mother to child?
In-utero
During delivery
During breast feeding
How common is mother-to-child spread in untreated patients?
25%
What is the mortality rate of HIV+ babies?
33% before 1st birthday
How common is HIV globally
Globally, 39 million people are living with HIV, with 37.5 million of these being adults (15+):
- 20 million - Women
- 17.4 million - men
Where in the world is the highest (and lowest) HIV incidence
There is a much higher incidence in Africa and a raised incidence in the americas:
- Sub-Saharan Africa
- Caribbean
- Thailand
Lowest rates are in the middle east
Most at-risk groups for HIV
- Men who have sex with men (MSM) 1:17 (1:7 in London)
- Black African men 1:25
- Black African women 1:23
- People who inject drugs 1:263
What are the 4 types of HIV screening programmes?
- Universal testing in high prevalence areas
- Opt-out testing in certain clinical settings
- Screening of high-risk groups
- Testing in the presence of clinical indicators
Who is tested in “universal testing in high prevalence areas”
All general medical admissions or all new GP registrations in:
High prevalence areas (>0.2%)
What services offer opt-out HIV testing due to high risk patients
- Termination of pregnancy services
- Sexual health services
- Addiction and substance misuse services
- Antenatal services
- Assisted conception services
How can HIV be tested for?
- Viral RNA
- Capsule protein p24
- HIV antibodies
What is detectible in the first 3 months on HIV testing?
Viral RNA
p24
What is detectable after 45 days on HIV testing?
Antibodies
How is antibody HIV testing carried out out
Fingerpick blood sample (Ready within 20-30 minutes)
What are some individual barriers to HIV testing
- Perceived risk
- Fear
- Confidentiality
What are some healthcare barriers to HIV testing
- Knowledge
- Experience
- Don’t want to offend
What are some structural and systemic barriers to HIV testing
- Cost
- Accessibility
- Stigma
What are some targets for antiretroviral drugs
- Reverse transcriptase
- Integrase
- Protease
- Entry - Fusion and CCR5 receptor (on host)
- Capsid
- Monoclonal antibodies
- Maturation (In the pipeline)
What is the main treatment regime for HIV
Highly active anti-retroviral therapy (HAART)
What is involved in highly active anti-retroviral therapy (HAART)
a combination of 3 drugs from at least 2 drug classes to which the virus is susceptible
Now available as a single tablet
What is the purpose of HAART
reduced viral load to undetectable levels, restores immunocompetence, reduces morbidity and mortality and prevents onward transmission
Why is it important that patients take HAART regularly
even some missed doses can lead to HIV resistance
How is life-expectancy affected in HIV
Life-expectancy is improviong towards normal
Young people started on HAART with a CD4>500 may have a longer life than those without HIV, however, the quality of life is worse
How can some HAART drugs affect other drugs
protease inhibitors - Liver enzyme inhibitors
NNRTIs - Potent liver enzyme inducers
What are some symptoms of HAART toxicity
GI side effects
Rashes, hypersensitivity, Stevens-Johnsons syndrome
Mood and psychosis
Renal toxicity
Osteomalacia
Increased MI risk
Anaemia
Hepatitis
What is the law on partner notification
It is a voluntary process by the patient (Murky if parter is also your patient as in a GP)
It is not a legal right for you to tell the partner in every situation
How does circumcision decrease HIV risk
Decreases risk by 60%
Foreskin contains a large number of CD4 cells
What are some HIV prevention techniques
- Condoms
- Regular testing
- PrEP and PEP
- PMTCT
- Circumcision
- Needle exchange/Drug treatment
What does U=U mean
Undetectable = Untransmittable
During treatment, if viral load is undetectable, HIV cannot be transmitted
What viral load is classed as undetectable?
<200 cp/ml
What form of transmission does not follow the U=U rule
Breastfeeding!
What is PrEP?
Pre-exposure prophylaxis
What is involved in PrEP?
combination of 2 anti-retroviral drugs given to those at high risk of HIV acquisition
This is usually Tenofovir/Emtricitabine daily or as a long acting injectable
What is a risk of PrEP?
risk to renal health and risk of drug-drug interactions so requires regular monitoring
What is PEP
Post-Exposure Prophylaxis
When should PEP be started?
within 72 hours of high-risk exposure, either sexual or occupational
What is involved in PEP?
This is a combination ART taken for 4 weeks consisting of:
- Tenofovir/Emtricitabine
- Raltegravir
How effective is PEP?
This is an unlicensed indication and has poor quality data to support, although in some cases shows an 80% reduction in HIV acquisition
How can vertical transmission be reduced?
- HAART during pregnancy
- Vaginal delivery if undetected viral load
- Caesarean section if detected viral load
- 2-4 weeks PEP for neonate
- Exclusive formula feeding
