SH Revision 1 Flashcards by patrick ellis

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State and describe 3 important structural genes of HIV [3]

Gag:
- nuclear proteins

Pol:
- viral enzymes: reverse transcriptase; integrase; protease

Env
- envelope glycoproteins

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Name three cell types that are infected by HIV [3]

All CD4 cells
T-Helper cells
Macrophages
- Microglia in Central Nervous System

Dendritic cells

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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

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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

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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)

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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

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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)

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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

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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.

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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.

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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

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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)

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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

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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)

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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

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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

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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)

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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

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Describe how would investigate and diagnose pulmonary cryptococcal infection (associated with HIV)

Chest X-Ray:
* Consolidation +/- cavitation,
* Interstitial infiltrates
* Effusions

Diagnosis:
- Bronchoalveolar lavage

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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

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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

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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/mmÂ³ 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/mmÂ³ 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/mmÂ³ 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/mmÂ³ 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** ## Footnote 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 ## Footnote **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 ## Footnote **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 ## Footnote *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**