SH Revision 1 Flashcards
State and describe 3 important structural genes of HIV [3]
Gag:
- nuclear proteins
Pol:
- viral enzymes: reverse transcriptase; integrase; protease
Env
- envelope glycoproteins
Name three cell types that are infected by HIV [3]
All CD4 cells
T-Helper cells
Macrophages
- Microglia in Central Nervous System
Dendritic cells
HIV
When you’re doing a HIV test, which antibody is being tested for? [1]
B cells produce ‘neutralising antibody: all patients, anti-gp120 Ab
HIV test is looking for anti-gp120-Ab
Describe brief overview of HIV immunoimpact
HIV affected cells:
* Reduced production of T cells (and all cells; pancytopenia common) – meaning naïve and memory cells in periphery
* Uncontrolled HIV replication occurs in naïve cells; causes chronic antigenic stimulation
* Get increased activated pool T cells and decreased memory, naïve T cells
* Having an activated pool of T cells targeted by HIV causes reduced replenishment of memory cells
* Become IC; and opportunistic infections occur
NB: the initial immune response is what causes first presentations of HIV
In the absence of treatment, HIV tends to follow a three-stage course; acute infection, chronic infection and late stage HIV / AIDs.
Give a brief overview of the Sx of each [3]
Similar to categories - but from Pulsenotes
Acute features
* sore throat
* lymphadenopathy
* malaise, myalgia, arthralgia
* diarrhoea
* maculopapular rash
* mouth ulcers
* rarely meningoencephalitis
Chronic Features
* After around six months the viraemia reaches a relative steady state. There is a period of stability in terms of the viral load, with a gradual fall in the CD4 lymphocyte count.
* patients tend to be asymptomatic for 8-10 years
AIDs/late-stage HIV:
There is a significant increase in the risk of developing AIDs defining illnesses and patients can present with fatigue, malaise, weight loss, opportunistic infections and malignancies due to:
* Neoplasms
* Infections (bacterial; viral; fungal and parasitic)
gp120 binds to which receptors on T cells [2] and macrophages [2]
gp120 binds to CD4 and CXCR4 on T cells and CD4 and CCR5 on macrophages
x
Diagnosis of primary HIV infection is primarily established through [], and a positive result must be confirmed using a second test.
Which further tests are given if a positive diagnosis is given? [+]
Diagnosis of primary HIV infection is primarily established through serum HIV enzyme-linked immunosorbent assay (ELISA), and a positive result must be confirmed using a second test.
- It detects both HIV-1 and HIV-2 antibodies as well as p24 antigen, a protein produced by the virus in early infection. A positive result warrants further testing to confirm the diagnosis.
Further tests:
* HIV-1/HIV-2 differentiation immunoassay
* HIV-1 viral load
* Genotypic resistance
* CD4+ T cell count
* Viral hepatitis serology
* Full STI screen (including syphilis serology)
Patients at risk of HIV can request home testing kits, either
Self-sampling kits to be posted to the lab
Point-of-care tests
What do each of the following test? [2]
Patients at risk of HIV can request home testing kits, either:
Self-sampling kits to be posted to the lab:
- fourth-generation tests for anti-gp120 antibodies and the p24 antigen
Point-of-care tests:
- antibodies only
Fourth-generation laboratory test for HIV checks for antibodies to HIV and the p24 antigen
It has a window period of [] days - what is the clinical significance? [1]
Point-of-care tests for HIV antibodies give a result within minutes. They have a [] day window period.
4th gen: 45 days:
- A negative result within 45 days of exposure is unreliable. More than 45 days after exposure, a negative result is reliable
Point-of-care tests for HIV antibodies
- give a result within minutes. They have a 90-day window period.
Name and describe the two key tests in the monitoring of HIV are [2]
How often does testing happen? [1]
Viral load: (HIV RNA by PCR)
- the aim of treatment is to achieve an undetectable viral load (< 20 or < 50 copies of viral genome/mL blood depending on the test).
- After treatment is established and suppression is achieved (a period in which testing is more frequent), testing tends to be repeated every 6-12 months.
CD4 count:
- measured more frequently after a new diagnosis and in those with low CD4 counts.
- Once established on treatment with a suppressed viral load and two readings > 350 a year apart routine testing is not necessarily needed.
Humoral response to HIV:
B cells produce a ‘neutralising antibody’ against [] in all patients, but this fails to clear the virus
B cells produce a ‘neutralising antibody’ against gp120 in all patients, but this fails to clear the virus
Know for general awareness
Describe the three different categories of HIV infection in adults [3]
CATEGORY A
* Acute HIV infection
* Asymptomatic HIV infection
* Persistent generalised lymphadenopathy
CATEGORY B:
* Baciliary angiomatosis
* Candidiasis (oral)
* Candidiasis, vulvo-vaginal, persistent, frequent or poorly responsive to therapy
* Cervical dysplasia (moderate or severe)/cervical carcinoma in situ
* Constitutional symptoms e.g. fever (> 38.5oC) or diarrhoea lasting >1 month
* Herpes zoster involving at least two distinct episodes or more than one dermatome
* Idiopathic thrombocytopenic purpura
* Listeriosis
* Oral hairy leukoplakia
* Pelvic inflammatory disease
* Peripheral neuropathy
Category C: (AIDS defining diagnosis)
Why are antibody test for HIV not useful in neonates? [1]
Which test should you perform [1] and at which time intervals? [3]
Antibody tests not useful in neonate because of presence of maternal antibody
HIV RNA PCR at:
* 1 - 3 days
* 4 - 6 weeks
* 8 - 12 weeks
HIV antibody at 18 months
A patient is newly diagnosed with HIV.
Which tests [2] would you perform and when? [1]
HIV antibody
- at baseline and at 3 months
HIV RNA by PCR (viral load)
Signs and symptoms of HIV x Candidiasis infeciton for:
- oral infection
- oesophageal infection
Oral:
* Asymptomatic
* Taste perversion
* Oral discomfort
* Pharyngeal discomfort on swallowing
* Creamy white plaques which may be stripped off from surface of tissue (in contrast to OHL)
* Erythematous patches
* Angular chelitis
Oesophageal infection:
* Dysphagia
* Retrosternal pain on swallowing (odynophagia)
* Nausea
* Creamy white plaques on endoscopy
Describe the treatment for oral / oesphogeal candida infection from HIV:
Topical tx [2]
Systemic tx [3]
Topical antifungals:
* Topical Nystatin / Amphoterecin lozenges
* Micanazole gel
Systemic antifungals (severe disease)
* Fluconazole 50-100mg/day
* If resistant e.g. long term use of Fluconazole or CD4< 50:
* Itraconazole
* IV Amphoteracin
A patient with HIV suffers a pathology which is suspected to have arisen from inhaling a pathogen from bird faeces. What is the name of the pathogen? [1]
Cryptococcus Neoformans (CN)
Cryptococcus Neoformans (CN) can impact which body systems? [3]
Describe the symptoms associated with each system being affected [+]
Skin:
- Umbilicated papules and ulceration
Lungs:
- Cough
- SOB
- Fever
Meninges & Brain:
- Asymptomatic (10%)
- Headache (most common symptom)
- Fever
- Mental change
Describe how would investigate and diagnose pulmonary cryptococcal infection (associated with HIV)
Chest X-Ray:
* Consolidation +/- cavitation,
* Interstitial infiltrates
* Effusions
Diagnosis:
- Bronchoalveolar lavage
Describe how would investigate and diagnose cryptococcal meningitis (associated with HIV)
DIAGNOSIS :
Serum:
- Crytococcal Antigens (CrAg)
CSF:
- High pressure; low glucose
- Indian ink test positive
- CRAG
- culture +/- lymphocytes
- low glucose; high protein; high pressure
CT:
- meningeal enhancement
- cerebral oedema
A patient is dx with cryptococcal infection. They have a stain perfomed which confirms the dx.
What is the type of stain used? [1]
Indian Ink
Describe the treatment for cryptococcal infection in HIV ptx:
Drugs [3]
Length [1]
IV Amphotericin
+/- Flucytoscine if severe
Then oral Fluconazole
Treat for 6 weeks minimum the repeat LP after this 6 weeks
Which medication can be given for CN prophylaxis in HIV patients? [1]
PROPHYLAXIS: Fluconazole 200-400mg/ day.
How do you treat PCP x HIV? [3]
If PCP pO2 < 10kpa? [2] (very severe infection)
TREATMENT:
* Co-trimoxazole 120mg/Kg in 3 divided doses/day
* IV Pentamidine
* Clindamycin and Primaquine
Severe infection:
* IV Methylprednisolone 40mg qds (5 -10 days)
* Oral Prednisolone 40mg bd
Describe the clinical presentation of HIV x toxoplasma gondii (TG)
Fever
Confusion
Headache
Drowsiness
Focal neurological signs: Fits
Describe the dx and mx of HIV x TG
DIAGNOSIS:
CT/ MRI:
* Ring enhancing lesions
* Classically multiple (but may be single lesions)
* Confirm diagnosis by response to treatment - repeat scan after 3-weeks.
Which infective organism is most likely in this PLWHIV? [1]
Cerebral toxoplasmosis
- demonstrates multiple small peripherally enhancing nodules located predominantly in the basal ganglia as well as the central portions of the cerebellar hemispheres. Only a small amount of surrounding oedema is present.
Describe the treatment for TG HIV [2]
TREATMENT:
Sulphadiazine (or Dapsone or Clindamycin) AND Pyramethamine
Change to oral when improved (total 6 weeks of treatment)
Prophylaxis for HIV x TG? [2]
Dapsone + Pyramethamine
HIV x brisk diarrhoeal illness = ? [1]
Cryptosporidium parvum
Dx of HIV x Cryptosporidium parvum? [2]
Tx? [1]
DIAGNOSIS:
Ziehl-Neelson staining of stool - may need up to 10
Rectal biopsy
TREATMENT:
* Difficult to eradicate if CD4 < 200, ART
* Paromomycin
Dx of Microsporidium species X HIV? [1]
Tx? [3]
Microsporidium species:
- immunofluorescent staining of stool
TREATMENT
* ART
* Albendazole
* High dose Erythromycin
Dx of Isospora belli x HIV? [1]
Tx [1]
DIAGNOSIS:
* Stool analysis
TREATMENT:
* Co-trimoxazole
Dx of Aspergillus fumigatus x HIV? [1]
Tx [2]
Symptoms:
Cough, fever, dyspnoea
DIAGNOSIS:
Chest X-Ray - may see cavitation Bronchoscopy
TREATMENT:
* Amphoteracin B
* Itraconazole
Dx of HIV x Histoplasma capsulatum (Histoplasmosis) [4]
- Chest X-Ray: diffuse infiltrates
- Pancytopenia
- Fungal blood cultures
- Biopsies of affected tissue
Tx for HIV x Histoplasma capsulatum OR Penicillium marneffei (Histoplasmosis) [2]
TREATMENT:
Itraconazole, Amphoteracin B
S&S of HIV x Histoplasma capsulatum (Histoplasmosis) [4]
SYMPTOMS:
* Fever
* Constitutional symptoms
* Respiratory disease.
SIGNS:
* Hepato-splenomegaly, enlarged lymph nodes, chest signs 10% rash (resembles folliculitis or molluscum)
* Neurological signs
Describe the difference in presentation in toxoplasmosis vs lymphoma presentation in people living with HIV [3]
Toxoplasmosis:
* Multiple lesions
* Ring or nodular enhancement
* Thallium SPECT negative
Lymphoma:
* Single lesion
* Solid (homogenous) enhancement
* Thallium SPECT positive
A CD4 count 200 - 500 cells/mm³ predisposes patients to which disorders due to infections from other pathogens [4]
Oral thrush
Shingles
Hairy Leukoplakia
Kaposi sarcoma
A CD4 count 100-200 cells/mm³ predisposes patients to which disorders due to infections from other pathogens [4]
Cryptosporidiosis (usually self-limiting)
Cerebral toxoplasmosis
Progressive multifocal leukoencephalopathy - JC virus
Pneumocystis jirovecii pneumonia
HIV dementia
Progressive multifocal leukoencephalopathy occurs secondary due to an infection by which virus? [1]
JC virus
A CD4 count 50-100cells/mm³ predisposes patients to which disorders due to infections from other pathogens [4]
Aspergillosis (secondary to Aspergillus fumigatus)
Oesophageal candidiasis (secondary to Candida albicans)
Cryptococcal meningitis
Primary CNS lymphoma (secondary to EBV)
A CD4 count < 50cells/mm³ predisposes patients to which disorders due to infections from other pathogens [2]
Cytomegalovirus retinitis
Mycobacterium avium-intracellulare infection
[] is a common complication of PCP
State 3 extrapulmonary manifestations of PCP [3]
Pneumothorax is a common complication of PCP:
* hepatosplenomegaly
* lymphadenopathy
* choroid lesions
Describe the clinical manifestations of Kaposi’s sarcoma [4]
presents as purple papules or plaques on the skin or mucosa (e.g. gastrointestinal and respiratory tract)
skin lesions may later ulcerate
respiratory involvement may cause massive haemoptysis and pleural effusion
Facial KS may present at the tip of the nose
Cutaneous KS is commonest, but can occur at any site, particularly gastro-intestinal tract (including the
Describe how you would treat KS [1]
Not all KS needs treatment – depends on site and severity of lesion
The most effective intervention is ART, which may be sufficient in up to 2/3 of cases
OTHER LOCAL TREATMENTS INCLUDE:
* Radiotherapy
* Cryotherapy
* Surgical excision (usually only for diagnosis)
* Intra-lesional injection of chemotherapy
* Cosmetic camouflage using make-up
Extensive or visceral KS may require systemic chemotherapy.
Describe which drugs might be used to treat this [4]
Bleomycin, etoposide and liposomal anthracyclines and paclitaxel may be used.
Name four maliganancies associated with HIV infection [4]
KS
NHL
Primary intracerebral lymphoma
Cervial and anal carcinoma
NB: Malignancies now most common cause of death in HIV patients
Shift from AIDS-defining cancers to non-AIDS-defining cancers:
Not associated with CD4 counts
Incidence not reduced by HAART
Which types of NHL are associated with HIV [2]
Large cell Lymphomas (2/3) - usually EBV associated
Burkitt’s Lymphomas (1/3), 40% are EBV positive
What is the treatment for HIV associated NHL? [4]
TREATMENT:
Chemotherapy - regimes vary but cyclophosphamide, doxorubicin, vincristine and prednisolone are used
commonly
CHOP
A patient is starting chemotherapy for their NHL associated with their HIV dx.
Which three drugs should be initiated [3] to protect agaisnt which infections [3]
Cotrimoxazole - PCP
Azithromycin - Mycobacterium Avium Intercellulare (MAI)
Fluconazole - Candida
Describe the type of lymphoma that is assocaited with primary intracerebral lymphoma [1]
Describe the symptoms of primary intracerebral lymphoma that is associated with HIV + [5]
Most lesions are high grade diffuse, large-cell immunoblastic B cell lymphomas that are
monoclonal and almost invariably associated with EBV
Symptoms:
* Headache,
* Confusion
* memory loss
* lethargy
* focal neurology and seizures
Which investigational findings would suggest a patient is suffering from primary intracerebral lymphoma
CT / MRI
- suggestive features: single or multiple lesions, crosses midline, peri-ventricular location.
LP
- EBV DNA in CSF
Investigations necessary to exclude extranodal lymphoma
- CT thorax / abdomen and pelvis, bone
marrow aspiration and trephine
Clinical non-response to 2-weeks of Toxoplasma
Brain biopsy provides definitive identification
- but is not always possible due to the location of
the lesion/s
Describe the treatment for primary intracerebral lymphoma associated with HIV [3]
TREATMENT:
* Radiotherapy (whole brain) is the mainstay of treatment
* Dexamethasone 4mg qds will reduce the oedema associated with the tumour and will provide an initial benefit
* Chemotherapy may be offered
HIV x HPV causes which cancers? [2]
Which HPV types are most commonly implicated? [2]
Anal and cervical
HPV 16 & 18
HPV also associated with penile, vulval, vaginal and oropharyngeal carcinoma
What screening do WIHIV have every year? [1]
HIV-infected women have yearly cervical cytology / colposcopy
