HIV Science

Question 1

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

Answer 1

Gag:
- nuclear proteins

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

Env
- envelope glycoproteins

Question 2

Why is timely diagnosis of primary HIV important? [2]

Answer 2

• The next time the patient becomes unwell may be at late stage of disease when prognosis
  may be poor
• Immediate ART initiation is recommended in all individuals diagnosed with PHI and

Question 3

HIV is a [], a genus within the family of retroviruses.

Answer 3

HIV is a lentivirus, a genus within the family of retroviruses.

Question 4

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

Answer 4

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

Dendritic cells

Question 5

HIV lifecycle

Answer 5

After entering a cell the enzyme reverse transcriptase creates dsDNA from the RNA for integration into the host cell’s genome

Question 6

gp120 binds to which receptors on T cells [2] and macrophages [2]

Answer 6

gp120 binds to CD4 and CXCR4 on T cells and CD4 and CCR5 on macrophages

Question 7

Describe the cytotoxic response of the body to HIV [1]

Answer 7

Cytotoxic lymphocytes (CTLs) can control HIV replication in early infection, but this is eventually
overcome by progressive damage to the immune system

Question 8

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? [+]

Answer 8

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)

Question 9

Humoral response to HIV:

B cells produce a ‘neutralising antibody’ against [] in all patients, but this fails to clear the virus

Answer 9

B cells produce a ‘neutralising antibody’ against gp120 in all patients, but this fails to clear the virus

Question 10

Know for general awareness

Describe the three different categories of HIV infection in adults [3]

Answer 10

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)

Answer 11

HIV is a disease of uncontrolled immune activation
HIV replicates in activated cells
- Chronic inflammation drives further HIV replication

Question 12

Describe brief overview of HIV immunoimpact

Answer 12

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

Question 13

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 each [3]

Similar to categories - but from Pulsenotes

Answer 13

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)

Question 14

HIV

When you’re doing a HIV test, which antibody is being tested for? [1]

Answer 14

B cells produce ‘neutralising antibody: all patients, anti-gp120 Ab

HIV test is looking for anti-gp120-Ab

Question 15

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]

Answer 15

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

Question 16

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.

Answer 16

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.

Question 17

Testing the CD4 count gives the number of CD4 cells in the blood. These are the cells destroyed by the virus. The lower the count, the higher the risk of opportunistic infection:

[]-[] cells/mm3 is the normal range
Under [] cells/mm3 puts the patient at high risk of opportunistic infections

Answer 17

Testing the CD4 count gives the number of CD4 cells in the blood. These are the cells destroyed by the virus. The lower the count, the higher the risk of opportunistic infection:

500-1200 cells/mm3 is the normal range
Under 200 cells/mm3 puts the patient at high risk of opportunistic infections

Question 18

A patient is newly diagnosed with HIV.

Which tests [2] would you perform and when? [1]

Answer 18

HIV antibody
- at baseline and at 3 months

HIV RNA by PCR (viral load)

Question 19

Name and describe the two key tests in the monitoring of HIV are [2]

How often does testing happen? [1]

Answer 19

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.

Question 20

Why are antibody test for HIV not useful in neonates? [1]

Which test should you perform [1] and at which time intervals? [3]

Answer 20

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

Question 21

Describe the presentation of primary HIV infection [+]

Answer 21

SYMPTOMS AND SIGNS OF PRIMARY HIV INFECTION
* Fever
* Sore throat
* Malaise / lethargy
* Arthralgia / myalgia
* Lymphadenopathy
* Rash
* Oro-genital or peri-anal ulceration
* Headache or meningism
* Diarrhoea
* Guillain-Barré syndrome (rare but well described in primary HIV infection)
* Sometimes CD4 may acutely fall low enough for acute conditions associated with
immunosuppression to occur such as:
* Oral Candida
* Shingle