HIV/AIDs Flashcards
Define HIV
Human immunodeficiency virus - retrovirus that preferentially infects and destroys cells of the immune system, in particular the CD4 class.
Often considered at a CD4 count less than 500
Define AIDs
Acquired ImmunoDeficiency Syndrome - complication of HIV. Describes the potentially life threatening infections and illnesses that happen when your immune system has been severely damaged by the HIV virus.
What are the risk factors for HIV/AIDS?
Recent travel to sub-saharafn Arifca (endemic)
White homosexual males
Black heterosexual females and children
Current or former partner with HIV
Area with high prevalence HIV
High risk sexual practices
History of injecting drug use
Sex workers
Occupational exposure such as needle stick injury.
What is the viral life cylce of HIV?
HIV attachment proteins gp120 on lipid envelope binds to target receptors primarily CD4+ and co-receptors CCR5 (initially) and CXCR4 (later stage infection). Targets T-helper cell, macrophages, dendritic cells.
gp41 causes fusion with cell membrane, content released into host cytoplasm, capsid fuses releasing viral RNA and proteins.
Proteases helps form functional proteins
Reverse transcriptase - creates pro-viral DNA from RNA.
pro-viral DNA enters nucleus and is instered into the host genome by integrase.
Host machinery produces new viral RNA -> viral proteins
Viral proteins move to cell surface and assemble to form new viral particles which are released surrounded by part of the host cell membrane
Cleaves glycoprotein forming a mature virus.
What is the pathophysiology of HIV/AIDS?
HIV infects mainly CD4+ T cells, resulting in progressive loss of T helper cells and immunodeficiency develops.
The patient develops characteristic cancers and infections
This leads to death over approximately ten years if left untreated.
What are the signs of a primary HIV infection?
First few weeks following infection
Mild to severe
Common - fever, sore throat, maculopapular rash, malaise, lethargy, arthralgia, myalgia, lymphadenopahty, oral/genital/perianal ulcers
Less common - headache, meningitis, CN palsies, diarrhoea and weight loss.
How does HIV commonly present?
Asympatomatic - found on screening in high risk individual
Unusually severe, prolonged, recurrent or unexplained infection
Conditions related to immunosuppression e.g oral candidiasis or shingles
Glandular fever-like illness
Lymphadenopathy of unknown cause
Pyrexia of unknown cause
Weight loss >10kg.
What are the two different types of HIV? How are they different?
HIV1 - 90% cases, higher viral load, more transmissable, weaker host immune response, more likely to progress to AIDs.
HIV2 - rare, West Africa and India, lower transmissibility, lower plasma viral load so less likely to progress to AIDs, stronger humoral host immune response against it.
How does the immune response against HIV actually aid the progression of the virus?
- HIV pro-viral DNA inserted into host genome, cytokine receptors activated on host T cell - triggers cell replication including genetic material - leads to HIV DNA expression increasing viral levels
- HIV infects DC, migrates to lymph node - abundant supply of host cells to infect
- Proliferation of activated T cells in the periphery increases the target number of cells for HIV.
What are the different phases of the HIV infection?
Eclipse phase: 0-3 weeks
Acute phase: 3 to 9 weeks
Chronic phase: 4 to 6 months onwards
What are the features of the eclipse stage of HIV infection?
Infects initial cells may replicate in local tissue - struggles to avoid eradication and achieve amplification/spread.
May trigger an antiviral interferon response
Spreads systemically via lymph nodes
Established reservoirs of infection
Invades GALT
Not yet detected by diagnostic tests
Lasts 8-10 days.
What are the features of the acute phase of HIV infection?
First detection in blood
Flu-like symptoms
Antibodies against HIV produced
May have a CD8+ response against HIV
HIV replicated rapidly and spreads throughout the body
High plasma HIV -detectable on test = high risk of transmission to others
What are the features of the chronic phase of HIV infection?
Viral set point established - may still replicate but at a very low level
Progressive CD4+ loss and increase in HIV numbers
Chronic inflammation
Tends to be asymptomatic
Progression to AIDs.
Describe the structure of the HIV virus.
Positive stranded RNA virus
Two identical dimerized RNA strands
Contains reverse transcriptase, protease and integrase.
Describe how the number of HIV/CD4+ cells change over the course of the disease.
- Initial - inc HIV and dec CD4+ acute phase - HIV invades CD4+ spreads to lymph nodes - established infection
- Recovery in levels - HIV decrease, CD4+ increase - effective level of immunity, depleted number of CD4+ to infect as killed by HIV
- Slow rise in HIV and drop in CD4+ = may change from CCR5 to CXCR4 co-receptor
As CD4+ levels decrease cretes immunodeficiency so less barrier to replication.
How is HIV spread?
Bodily fluids
Unprotected sexual intercourse - most common
Vertical transmission - in utero - from mother to child - or from breast milk
Blood transfusion - very rare.
Sharing needles
Occupation - NSI and splash
What is the prognosis like for HIV?
If adherent and clinically responding to ART - normal or near-normal life expectancy.
Early diagnosis and prompt ART reduced mortality and morbidity.
What are some complications of HIV?
Advanced HIV disease or AIDS - opportunistic infections, malignancies
Wasting and diarrhoea - advanced disease or opportunistic infection
Neurological problems - HIV associated dementia or side effect of ART
Mental health problems - depression, substance abuse
Metabolic abnormalities (dyslipidemia and insulin resistance) and cardiovascular disease including MI
Renal disease
Bone disease - osteoporosis.
When should you suspect HIV in infants/children?
Failure to thrive
Pneumocystis pneumonia
Cytomegalovirus disease
HIV enceophalopathy
Recurrent infection
Severe presentation of common childhood infections
Chronic diarrhoea
Herpes zoster
Severe pneumonia
TB
Lymphadenopathy
Any AIDS-defining conditoins
When might a HIV test be offered to a asymptomatic person?
Pregnancy - routine antenatal screening
Primary care - if requested, risk factors, another STI, AIDS defining condition or indicator conditions
Newly registered with GP or having blood test and not had HIV test in 12 months and in high prevalence area.
What is meant by a HIV indicator condition and a AIDS defining condition?
HIV indicator - medical conditions associated with undiagnosed HIV infection, 1 or more per 1000 people with conditions will have HIV
AIDS defining - type of HIV indicator, associated with a lower CD4+ count, these patients are often already diagnosed with HIV.
What are the different threshold CD4+ counts for different stages of HIV/AIDS?
Below 500 is abnormal - may indicate HIV
Below 300 = advanced HIV
Below 200 is indicative for AIDs.
What are the different HIV indicator conditions at CD4 <500?
TB
HPV
Shingles
Hairy leukoplakia
Karopsi sarcoma (skin cancer purp/red/brown flattened or raised)
Burkitts lymphoma - non hodgkins lymphoma
What HIV indicating conditions are present as a CD4 <300?
Pneumocystic jvovecy pneumonia
Oesophageal candidiasis
HIV associated dementia
What are the AIDS defining conditions found at CD4 <100?
Mycobacterium avium (<50)
Toxopasmosis
CMV
What are the clinical manifesations of AIDs by system?
Immune - l wcc <200/mm3 = AIDs, opportunistic infections, lymphadenopathy, fatigue
Integumentary - poor wound healing, skin lesions, night sweats
Respiratory - cough, SOB
Gastro - diarrhea, weight loss, nausea, vomiting
CNS - confusion, dementia, headache, visual changes, personality changes, pain, seizures
What opportunistic infections are more common in AIDs?
Pneumocystis carinii pneumonia
Toxoplasmosis (encephalitis)
Cryptosporidiosis
Candidiases - esophageal/vaginal
Mycobacterium complex
TB
Cytomegalovirus
HSV
Varicella-Zoster Virus
What malignancies are more common in AIDS?
Kaposi sarcoma
Non-Hodgkin lymphoma
Hodgkin Lymphoma
Invasive cerical carcinoma
What is the AIDS dementia complex?
70% of AIDS clients will present with cognitive, motor and behavioural impairments.
What is the management for a new HIV diagnosis?
Refer urgently to a specialist HIV clinc - preferably within 48 hours to 2w after testing.
Advise on support services and safer sexual strategies and spread reduction.
What are the different drug classes of Antiretroviral therapy available for HIV?
NRTI - tenofovir, abacavir
NNRTI - doravirine
Protease inhibitor - ritonavir
Fusion inhibitor - enfuviritide
What diagnositic tests can be used to confirm HIV?
Antibodies to HIV may not be present
HIV PCR and p24 antigen test can confirm diagnosis.
- HIV Antibody/Antigen test - initial screening - positive result indicates further testing needed/
- HIV RNA viral load - measures virus in the blood
3.HIV confirmatory test - HIV-1/2 antibody differentiate immunoassay
4. CD$ T cell count - suggestive
5. Resistance testing - genotypic resistance before ART to help predict treatment efficacy.
What other background health checks are useful in a suspected HIV patient?
Full blood count
Liver and renal function tests
Lipid profile
Glucose level
Hepatitis B and C Serology
Tuberculosis screening
STI screening
Immunisation status review
What combination of drug classes is typically used as HAART therapy?
Two NRTI and a protease inhibitor or a NNRTI.
THis decreases viral replication but also reduces the risk of viral resistance emerging.
This skin change is seen in a known HIV patient, what is it? What conditions is it likely?
Caused by HHV-8
Causes small blood vessel to grow abnormally
Purple/brown plaques or papules on skin or mucosa
Inlcuding legs, face, mouth and genitalia.
May ulcerate
May cause pleura effusion and hemoptyis if respiratory system involvement
Is Kaposi sarcoma
Give some timelines for HIV infections
Symptomatic phase - 1 to 2 weeks after infection
Detactable on test - 3 to 4 weeks after infection
Asymptomatic phase - can last up to ten years if left untreated
How does the Med1 team summarise the life cycle of HIV?
1 = attachment (fusion of the viral membrane with the cell membrane)
2 = fusion allows HIV capsid to enter the cel. GP41 proteins helps fuse envelope wit the cell wall, capsid release the viral RNA, reverse transcriptase and integrase
3 = Reverse transcriptase - viral RNA to pro-viral DNA inside cell
4 = integration. Integrase enzyme carries viral DNA into cell nucleus, and inserts to host DNA
Latenchy phase
5 = transcription - makes messenger RNA
6 - translation mRNA is used to make protein from the virus
7 = assembly and release
8 = maturation
When are people with HIV most infectious>
Shortly after infection
What are the symptoms of HIV in the first few weeks after infection?
Known as seroconversion illness
Flu like - fever, headache, rash or sore throat
What are the symptoms of HIV as the infection progresses?
Swollen lymph nodes
Weight loss
Fever
Diarrhoea
Cough
What is seen in this image?
Oral hairy Leucoplakia
Caused by EBV
Found almost exclusively in people with HIV
Adherent corrugated white patches on lateral parts of tongue that cannot be scrapped off.
Occurs when CD$ count is 200-300 or lower
What is seen in this image?
Oesophageal candidiasis
White plaques on buccal and pharnygeal mucosa
Lesions can be scarpped off
Can cause pain on eating and swallowing = weight loss
Common infection in people living with HIV
What is cryptosporidium?
Protozoan infection, acquired through ingestion of contaminated water or food
Self limiting in immunocompetent, chronic diarrhoea, abdo cramp and weight loss in people with HIV
CD4 <200
Diagnosed on stool microscopy or PCR
What is toxoplasmosis?
A protozoan parasite
Commonest cause of brain lesion in people with HIV
Usually due to reactivation of previous infection, causes focal neurological symptoms, fever and seizures
Can also cause chorioretinitis.
What is this?
Shingles
Caused by herpes zoster virus
Painful vesicular lesion in a dermatomal distribution
Complications include post herpetic neuralgia, blindness and meningitis
What is pneumocystis jiroveci pneumonia?
Commonest cause of infection in patients with HIV
Fungal infection of the lungs
Presents with progressive dysponea, fever, malaise
Desaturation on exertion, CXR shows diffuse alveolar infiltrates
Diagnosis is by PCR of induced spututm of BAL or histology
What is shown in this MRI? Related to HIV
Progressive multifocal leukoencephalopathy
Rare brain and spinal cord disease is caused by JC virus, seen almost exclusively in people with HIV
Symptoms include loss of muscle control, paralysis, blindness, speech problems and altered mental state
Disease often progresses rapidly and may be fatal.
What condition is this related to HIV?
Mycobacterium tuberculosis (ZN stain)
Symptoms in the lungs include cough, tiredness, weight loss, fever, haemoptysis and night sweats
Organisms are acid fast bacilli
What conditions is this related to HIV?
CMV - type of herpes virus causes pneumonia, colitis, encephalitis and retinitis.
Can cause blindness if not treated promptly
What is cryptococcus neoformans related to HIV?
Common cause of meningitis in HIV
Presents with insidious onset of fever, headache, visual change, neck stiffness, cranial nerve deficits and seizures
Associated with CD4 count <100 cells/mm3
Diagnosed by India ink staining of CSF or antigen test.
