Positive HIV serology Flashcards
1
Q
What type of virus is HIV?
What types of HIV are there?
A
- HIV –> lentivirus group of retrovirus family
- Two types of HIV, HIV1 and HIV2
- HIV1 most frequently occuring strain globally, HIV2 almost entirely confined to west africa (has been some spread to europe - France + portugal).
- HIV2 - more low grade disease, associated with immunosuppression and AIDS but many drugs in HIV1 are ineffective in HIV2.
2
Q
Epidemiology of HIV - where are regions of high infection rates/prevalence?
A
- Sub-saharan africa remains most seriously affected
- eastern europe and central asia –> infection rates continue to rise
- In UK:
- M:F 70:30
- total number of people living with HIV continues to rise
- sustained new infections and falling death rates (mortality falls, poeple living with HIV are older, 1/4 > 50 yrs)
- approx 1/4 HIV infected in UK undiagnosed and unaware until late diagnosis –> poorer outcome and onward transmission
3
Q
Define HIV
Define AIDS
A
- HIV = pandemic infectious disease –> caused by retrovirus that infects and replicated in human lymphocytes and macrophages
- erodes integrity of human immune system over a number of years
- culminates in immune deficiency and susceptibility to a series of opportunistic infections and development of certain malignancies
- AIDS = a syndrome of a constellation of infections/conditions or malignancies) occurs as a result of HIV infection, develops over 10-15 yrs.
4
Q
What are the infection routes of HIV?
A
- HIV infection –> majority via semen, cervical secretions and blood
- most significant marker for transmission is the HIV viral load, which is highest in acute infection and reduced by effective ART
Routes of acquisition:
- Sexual intercourse --> vaginal and anal, more efficient from men to women and to receptive partner in anal intercourse, both homosexual and heterosexual transmission (50:50 in uk)
- mother to child transmission --> transplacental, perinatal, breast feeding. Majority of infections take place perinatally, breast feeding doubles risk of transmission. Risk in UK low.
- Contaminated blood/blood products/organ donations –> blood products screened in UK.
- contaminated needles –> IV drug misuse, injections and needle stick injury –> sharing needles and syringes for IV drug use major route.
5
Q
What is the structure of the HIV virus?
A
- Two molecules of single stranded RNA within nucleus
- reverse transcriptase polymerase cinverts viral RNA into DNA
- protease includes integrase
- p24 = core protein –> levels can be used to monitor HIV disease
- p17 = matrix protein, gp120 is outer envelope glycoprotein which binds to cell surface CD4 molecules
- GP 41 –> transmembrane protein influences infectivity and cell fusion
6
Q
Pathogenesis of HIV infection?
A
- initial exposure –> virus transported by dendritic cells from mucosal surface to regional lymph nodes where permanent infection is established
- HIV surface glycoprotein gp120 binds to CD4 receptor molecule (plus coreceptors ccr5 AND cxcr4)
- Fusion –> subsequent conformational change, results in fusion between gp41 and cell membrane
- Reverse transcription –> entry of viral capsid, uncoating of RNA, DNA copies made, DNA polymerase from host cell leads to formation of dsDNA
- Integration –> virally encoded DNA inserted into host genome
- Transcription –> Regulatory proteins control transcription –> RNA molecule now synthesised from DNA template
- Budding –> virus reassembled, buds out from host cell
7
Q
LO: Understand the incubation period for HIV infection
A
- Primary HIV infection = first 6 months following HIV acquisition. Period of uncontrolled viral replication –> high levels HIV circulating in plasma and genital tract (highly infectious)
- Incubation period = 2-4 weeks post infection- silent both clinically and serologically
-
Acute retroviral syndrome: 3-6 weeks post infection number of patients develop self limiting acute viral illness
- up to 60% asymptomatic
- HIV frequently not considered in differential
-
Seroconversion: lasts 2-4 weeks, normally within 3 weeks of infection, can develop 2-8 weeks after!–> seroconversion is the period in which the body starts producing detectable levels of HIV antibodies.
- During seroconversion symtoms of: fatigue, fever, sore throat, headache, body ache, swollen lymph nodes, maculopapular rash (symptoms usually last 14 days)
- Clinical latency/asymptomatic chronic infection –> majority asymptomatic for substantial time, but variable (Average ~7 years). Virus continues to replicate and individual is infectious. Gradual decline in CD4 count over approx 10 years before symptoms or AIDS appear. Some progress faster, with rapid decline in CD4 over 2-5 yrs.
8
Q
LO: understand the timing of serological tests
What is a window period?
A
- Window period = time between initial exposure and positive serology (seroconversion)
Tests:
- viral load –> PCR of HIV viral RNA --> shortest window period (1-2 weeks) but only sensitive 1 week before seroconversion, less accurate and timely so rarely used.
- p24 antigen (capsid protein)—> average 16 days to appear, most 1-8 weeks
- ELISA for HIV antibodies –> Shortly after infection IgM AB’s to HIV appear, then 3-4 weeks later IgG antibodies (almost all detectable within 6 months). During this time can get false negative in window period. 4th generation reduced period 2-4 weeks.
- 4th generation ELISA and p24 antigen (capsid protein) –> detects both anti-HIV antibodies and p24 antigen. Average 10 days. 1st line testing. Detects 95% of infection within 4 weeks. Confirm with second test 3 months later as 5% take longer.
- Negative test result needs to be confirmed with second test 3 months after exposure.
9
Q
LO: sensitively explain when pre and post test HIV counselling is appropriate
Pre test HIV counselling: what is involved?
A
Pre-test discussion:
- Purpose –> establish informed consent for HIV testing
- Should cover:
- benefits of testing to individual
- details of how results are given: face to face provision of results encouraged for ward patients, those likely to have HIV+ve, mental health risk, english 2nd language, under 16’s, highly anxious or vulnerable.
- Explain reason for testings –> may need more explanation if patient isn’t expecting it (persistent candidiasis)
- In case of refusal –> explore reasons
- explain possible outcomes –> positive result - what will happen, negative –> potentially window period, may need another test
- Written consent not needed, document in notes
10
Q
Post test discussion - what is involved?
A
- Negative result -> offer STI screen, positive sexual health promotion, retesting after 3 months due to window period
- Positive result –> SPIKES, translator if non english speaking, refer to specialist HIV clinician within 48 hours (no alter than 2 weeks), reassure and inform what will happen from here: more testing, medications, HIV now a long term condition that can be managed not a fatal diagnosis. Most people have normal lifespan nowadays.
11
Q
LO: Explain why detecting and diagnosing HIV early in the course of infection is important –>
allows for early treatment
slows or stops progression of AIDS
modification of behaviour to prevent spread of disease
in pregnant women tx reduces rate of transmission to her child
A
- Previously –> started ART when CD4+ count was less than 350 cells / mm3 OR symptomatic
- NOW: treat EVERYONE from first diagnosis regardless of CD4+ cell count
- starting ART immediately vs deferred –> 57% decreased risk of all causes mortality and morbidity, decreased risk of AIDS morbidity/ mortality by 72%
- ART in UK –> 94% are virally suppressed –> limited chance of disease transmission
- life expectancy can match that of general population in those wh ostart ART early
- Delayed treatment in more advanced cases compromises clinical outcomes
- Pregnancy –> pregnant women should be offerred screening. Risk of vertical transmission increases withviral load. If positive start on ART + C section delivery, avoid breastfeeding –> transmission reduces from 30% to less than 1%.
12
Q
Lo: explain the immunological defects in AIDS and its manifestations (oral, glandular, skin, lungs)
1) Symptoms of seroconversion
A
- Fever
- Aches - arthralgia, myalgia
- lethargy
- lymphadenopahy
- sore throat
- mucosal ulcers
- transient pink maculopapular rash
- neurological –> headache, photophobia, myelopathy (injury to spinal cord), neuropathy, rarer encephalopathy.
- Lasts up to 3 weeks and recovery is usually complete.
13
Q
What are the different types of immunodeficiency?
A
- Primary immunodeficiency (intrinsic cause = usually genetic)
- phagocyte deficiencies (innate cell mediated immunity)
- complement deficiencies (innate humoral immunity)
- severe combined immunodeficiencies (adaptive cell mediated immunity)
- predominantly antibody deficiencies (adaptive humoral immunity)
- Secondary immunodeficiency (extrinsic cause = non iatrogenic)
- hypospelnism/asplenism
- haemotological malignancies
- HIV/AIDS
- Immunosuppresion (extrinsic cause = iatrogenic)
- steroids and immunosuppresants
- cytotoxic chemotherapy
- total body irradiation (before bone marrow transplantation)
14
Q
Explain the timeline of HIV infection
From initial exposure to the development of AIDS
A
- Exposure to seroconversion: CD4+ count drops to ~500 cells/mm3 = acute retroviral syndrome (within 2-4 weeks)
- Seroconversion to AIDS: clinical recovery, CD4+ cells rise to a set point and the viral load decreases simultaneously. Then over 8-10 years CD4+ count gradually decreases, viral load gradually increases.
- AIDS: defined by CD4+ count < 200 cells/mm3 OR any AIDS defining condition. Symptoms start to appear around 7/8 years, opportunisitic infections and sx of aids –> death.
15
Q
Classifications of AIDS?
A
- Multiple classification systems exist –> widely used is CDC classification
- Based on cell counts and symptoms/ AIDS defining illnesses
Cell counts: CD4+
- 1 > = 500
- 2 200-499
- 3 < 200
Clinical categories:
- HIV category A: Asymptomatic, acute infection/seroconversion or persistent generalised lymphadenopathy
- HIV category B: symptomatic, but NO AIDS defining illnesses e.g. oral candidiasis, herpes zoster, PID, peripheral neuropathy
- HIV category C: AIDS defining condition
16
Q
What are the AIDS defining conditions?
A
Fungal:
Candidiasis of bronchi/trachea/lungs/ oesophageal
Coccidioidomycosis - fungal spores inhaled
cryptococcosis - lungs or brain
Respiratory
Pneumocystic pneumonia (caused by fungus Pneumocystis jirovecii) or pneumococcal pneumonia (Recurrent)
Herpes simplex chronic ulcers, bronchitis, pneumonitis, oesophagitis
mycobacterium tuberculosis - TB (any site) or other mycobacterium
Nervous system:
CMV retinitis (with loss of vision)
Encephalopathy HIV related
Toxoplasmosis of brain (cerebral toxoplasmosis)
salmonella septicaemia
progressive multifocal leucoencephalopathy
Cancerous:
Kaposi’s sarcoma (HHV8)
Burkitt’s lymphoma
lymphoma (primary) of brain
cervical carcinoma - invasive
Intestinal/GI:
Cryptosporidiosis = parasite causing diarrheal disease
Intestinal isosporiasis =parasite Isospora belli
Viral: herpes simplex virus (chronic ulcers), cytomegalovirus disease
PLUS wasting syndrome - due to HIV
17
Q
Explaining the immunological defect in AIDS
A
- Virus transported from dendritic cells at mucosal surface to regional lymph nodes where permanent infection is established
- HIV surface glycoprotein gp120 recognises CD4 molecules (along with coreceptors CCR5 and CXCR4), enters T cell.
- Viral replication via reverse transcriptase, integrase and budding occurs
- Lymphocytes in GI tract are heavily infected early in process - become rapidly depleted
- viral production by infected cells lasts around 2 days - limited by cell death
- progressive loss of activated CD4 T lymphocytes due to killing by CD8 cells = key factors in immunopathogenesis of HIV
- NK cells also involved in human immune response but escape mutations in virus population (high level of mistakes in RT enzyme) compromises antiviral effect.
- Production of neutralising antibodies occurs 12 weeks after infection
- resulting cell mediated immunodeficiency leaves host open to opportunistic infections
- T cell activation occurs early, which leads to an increase in the number of susceptible CD4 bearing target cells that can become infected and destroyed.
- Inflammatory state in HIV –> HIV itself plus other co-pathogens (e.g. CMV), translocation of microbial products (lipopolysaccharides) from gut to systemic circulation, raised cytokines and coagulation system activation.
- May leads to HIV associated end organ damage, higher risk MI and malignancy
18
Q
HIV: oral manifestations?
A
- oral candiasis
- oral hairy leukoplakia
- angular chelitis (cracking at corners of mouth due to fungal infection)
- ulcers
20
Q
HIV: skin manifestations?
A
- Rashes may occur throughout HIV disease
- WHO stage 2 disease
- Herpes zoster - shingles
- viral skin infection - molluscum contagiosum, viral warts
- seborrhoeic dermatitis (recurrent and severe)
- pruritis papular eruptions - extremities
- folliculitis with urticarial lesions
- fungal skin and nail infections - tinea cruris (jock itch), tinea pedis
- Kaposi’s sarcoma
- Scabies
- severe/ recalcitrant psoriasis
