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Immunology > HIV > Flashcards

HIV Flashcards

1
Q

Pathogenesis of HIV-1 infection

A

HIV-1 infection –> enters and replicates in CD4+ cells i.e. helper T lymphocytes –> infected CD4+ cells are recognised and attacked by CD8 (cytotoxic) cells –> progressive loss of CD4+ T cells –> AIDS

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2
Q

Typical course of HIV-1 infection

A

1) Acute HIV syndrome
- HIV viral load spikes
- CD4+ dips (killing of CD4+ cells by CD8+ cytotoxic cells = seroconversion illness)
- B lymphocytes also make ab to HIV (seroconversion illness)

2) Clinical latency
- HIV viral load suppressed
- CD4+ recovers slightly then falls over time
- CD4+ is going to be WNL

3) AIDS symptoms
- HIV viral load increases exponentially
- CD4+ continues to fall

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3
Q

What’s seroconversion illness in HIV?

A

Phase 1) Acute HIV syndrome

10 days to 6 weeks post acquisition of HIV-1
Non-specific symptoms similar to glandular fever
Typically self limiting

Non-specific characteristics typical of viral infections

  • Fever, pharyngitis, myalgia/arthralgia
  • Lymphadenopathy & maculopapular rash
  • Aseptic meningoencephalitis; GBS
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4
Q

What’s AIDS?

A

Final stage of untreated HIV-1 infection
Terminal without treatment
Uncommon but not rare

Marked by:

1) CD4+ ≤200 cells
2) AIDS-defining conditions
- Opportunistic infection e.g. PJP, candida
- Malignancy

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5
Q

What’s the clinical latency phase?

A

Most patients are asymptomatic for long periods of time
CD4+ ≥500

Various symptoms not uncommon
Not usually directly caused by HIV
- Psoriasis
- Persistent generalised lymphadenopathy
- Herpes zoster
- Apthous ulcers
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6
Q

AIDS CD4+ ≤200 associated conditions

A

Oesophageal candidiasis - usually candida albicans

PJP

TB

Lymphoma

Kaposi’s sarcoma

  • Extremely vascular tumour
  • Skin most common - lung, gut occasional
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7
Q

AIDS CD4+ ≤~100 associated conditions

A

Cerebral toxoplasmosis

  • Seizures
  • From cat faeces or uncooked meat

Cryptococcal meningitis

  • Respiratory entry –> haematogenous spread
  • Screened by serum cryptococcal antigen
  • Can be triggered starting anti-retroviral therapy

Cryptosporidiosis

  • Chronic diarrhoea
  • Difficult to treat//eradicate

Can occur at higher CD4 counts

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8
Q

AIDS CD4+ ≤50 associated conditions

A

CMV infection

  • Usually reactivation
  • Broad manifestation - retinitis (blindness), enteritis, pneumonitis, encephalitis

MAC
- Lymphadenitis, pulmonary infection

Primary brain lymphoma

  • Seizure
  • Skin most common (lung, gut occasional)

PML

  • Reactive disease, caused by the JC virus
  • No effective treatment
  • Fatal unless HIV controlled
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9
Q

How is HIV transmitted?

A

1) Blood
2) Seminal
3) Vaginal secretions
4) Breast milk

5) Mother to child vertical transmission
- Basically eradicated due to effective anti-viral therapy

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10
Q

Life cycle of HIV

A

HIV virion –> attaches to CD4+ helper T cells via surface molecules (CD4 protein + coreceptor) –> virion fuses with host cell membrane –> contents of virion spill out into cytoplasm –> RNA is reverse transcribed into DNA –> viral DNA is actively transported into nucleus and integrated into cell genome –> host+viral DNA is transcribed and translated to viral proteins –> proteins get packaged up to make new virion –> bud off from cell –> uses protease to mature –> infect other helper T cells

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11
Q

Why do we use combination ART rather than monotherapy?

A

To prevent resistance

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12
Q

Should we start ART immediately or wait until CD4+ ≤50?

A

Immediately
Reduce AIDS events, death, malignancy
Higher mean CD4+ count

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13
Q

What are the 4 key ART classes?

A

1) Nucleoside reverse transcriptase inhibitors (NRTIs)
2) Non-Nucleoside reverse transcriptase inhibitors (NNRTIs)

3) Protease inhibitors (PIs)
- Always need booster (CYP450 inhibitors) to increase PI drug level
- High barrier to resistance
- May increase cholesterol levels

4) Integrase strand transfer inhibitors (INSTIs)
- Preferred anchor option

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14
Q

How to start ART in HIV?

A

TRIPLE THERAPY

2 NRTIs + one of

  • NNRTI
  • PI (boosted)
  • Integrase inhibitor
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15
Q

Which ART to start in HIV?

A

TRIPLE THERAPY

TRIPLE THERAPY
x2 NRTI backtone + x1 integrase inhibitor (anchor)

1) Preferred NRTI backbone options
Tenofovir alafenamide + emtricitabine (preferred)

Abacavir + lamivudine

Come in combination tablet
Researched most in clinical trials

2) Integrase inhibitors are the preferred anchor drug class
- Very potent, drop viral load quickly
- Well tolerated, low drug-drug interactions
- Bictegravir or dolutegravir (2nd gen integrase inhibitor)

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16
Q

Current approved integrase inhibitors

A

1st gen

  • Raltegravir
  • Elvitegravir

2nd gen (less resistance) preferred
Dolutegravir
Bictegravir

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17
Q

What’s high and low HIV viral load?

A

> 100,000 high

<100,000 low

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18
Q

Why is HLAB5701 important in HIV?

A

1) If positive, associated with hypersensitivity to abacavir (NRTI)
= Contraindicated

2) People with HLAB5701 is able to hold the HIV peptide (presents it to the cytotoxic T cell) more strongly which strongly stimulates cytotoxic T cell response

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19
Q

Why is CV disease/risk important to consider in HIV?

A

Avoid abacavir

Increased risk of myocardial infarction

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20
Q

Which NRTI to choose if there is renal impairment or osteoporosis?

A 
Tenofovir alafenamide (TAF)
Minimal effects on kidneys and bone

Avoid Tenofovir disoproxil fumarate (TDF) - older version of tenofovir - associated with renal toxicity and bone density loss

21
Q

What about 2 drug cART?

A

Dolutegravir (integrase inhibitor) + lamivudine (NRTI)

NEW double therapy approved for initial cART
Emerging evidence

Logic to use 2 instead of 3 drugs is reduce side effects and drug interactions however not recommended with

  • Plasma viral load >500,000 copies/mL
  • Hep B coinfection
  • No available resistance genotyping results
22
Q

HIV diagnosis + baseline investigations

A 
Screening test (P24 Ag/Ab ELISA test) 
If positive, do confirmatory test (Western blot)

Others
HIV-1 RNA plasma viral load
CD4+ lymphocyte count
HIV-1 resistance genotyping

Specialised testing
TB-IGRA (latent TB)
HLAB5701 (for abacavir hypersensitivity)

Other
STIs - hep B, C coinfection

23
Q

What’s a confirmatory test for HIV?

A

HIV-1 Western blot
If you have a certain combination of bands = confirmed
Reported by visual inspection (degree of subjectivity)
Highly specific, poor sensitivity

24
Q

Can you use viral load to diagnose HIV?

A

No

25
Q

how long do HIV antibodies/serology take to be positive after innoculation?

A

14 days

26
Q

What’s the p24 antigen?

A

Included in screening (together with HIV ab)
Detects infection during seroconversion
p24 declines rapidly post-seroconversion (limits utility to early or very late infection)

27
Q

Where in the HIV life cycle do NRTIs/NNRTIs work?

A

inhibits reverse transcriptase of viral RNA to DNA inside T helper cells

28
Q

Where in the HIV life cycle do integrase inhibitors work?

A

Stop viral DNA from integrating with the host DNA

29
Q

Where in the HIV life cycle do protease inhibitors work?

A

After the new virion is made and buds off from the T helper cell, it needs protease to mature. We block this maturation process.

30
Q

Which class of HIV therapy achieves a particularly rapid reduction in viral load?

A

Integrase inhibitor - preferred anchor agent

31
Q

What’s the difference between PrEP and PEP?

A

PrEP is pre exposure prophylaxis

PEP is post exposure prophylaxis

32
Q

How soon do you have to take PEP to prevent HIV infection?

A

Within 72 hours

The sooner the better

33
Q

Who gets PrEP?

A

People with behaviour that pose high risk of HIV acquisition
Need to take it consistently
Course is 3/12 but could take it for years
90-99% efficacy

34
Q

Who gets PEP?

A

3 drugs for risk >1/1000
2 drugs for risk <1/1000 but >1/10,000

1) Non-occupational exposure + known HIV source not on treatment or on treatment with detectable/unknown viral load
- Exclude oral sex
- 3 drugs recommended

2) Occupational exposure + known HIV source
- NSI, mucous membrane and non-intact skin exposure
- 3 drugs recommended if detectable/unknown viral load; consider 2 drugs if undetectable viral load

Criteria bit tricky in those with unknown HIV status - depends on MSM, high prevalent country, type of exposure

35
Q

How long is PEP?

A

28 day course

36
Q

When do you check HIV serology and viral load after HIV exposure?

A

Immediately after exposure - to make sure they don’t already have HIV (consider PEP if within 72h)

4-6 weeks

3 months

Also do

  • Hep B and C serology
  • Syphilis serology
37
Q

Which drug regime do we use for PrEP?

A

Tenofovir (TDF) + emtricitabine

38
Q

What drug regimes do we use for PEP?

A

2 drug regimen
Tenofovir (TDP) + emtricitabine OR lamivudine

3 drug regimen
Your preferred 2 drug regimen PLUS
Dolutegravir OR Raltegravir OR Rilpivirine

39
Q

What’s important to monitor while on PrEP?

A

Could take it for years

Monitor eGFR and ACR (tenofovir is renal toxic)

40
Q

PJP clinical presentation

A

Often look quite well but majorly desaturate on exertion
Dyspnoea
Fever
Dry cough

Less common
Weight loss
Chest discomfort
Chills
Haemoptysis

Chest exam often normal

41
Q

Chest radiology PJP

A

Basal and apical sparing

CT: widespread ground glass changes

42
Q

Diagnosis of PJP

A

Sputum PCR - sens 50-90%, spec 99%

BAL - diagnostic yield >90%

43
Q

What test to rule out PJP?

A

Serum beta-D-glucan is useful to rule out PJP

44
Q

Treatment PJP

A

Bactrim +/- steroids (if hypoxic)

45
Q

When do give PJP prophylaxis in HIV?

What to give?

A
  • New diagnosis of HIV and CD4 <200 (can stop when CD4 >200 or viral load controlled)
  • Following episode of PJP

Bactrim daily or 3 times a week

46
Q

Cryptococcus in HIV

1) Type of pathogen
2) Most common strain
3) Complication

A

1) Yeast
2) Cryptococcus neoformans neoformans
3) Meningitis - subacute/indolent headache and fever, behavioural change, confusion (doesn’t present like typical bacterial meningitis)

47
Q

Diagnosis of cryptococcal meningitis in HIV

A

LP

  • High opening pressure
  • Mildly raised WCC and protein, low glucose
  • India ink and CRAG positive (serum CRAG can be helpful)
48
Q

Treatment cryptococcal meningitis in HIV

A

1) LP can reduce opening pressure and control sx
May need to repeat LP or shunt or drain to alleviate high pressure

2) Amphotericin + flucytosine (5FU) 2 weeks –> fluconazole 8 weeks as secondary prophylaxis until CD4 count comes up

49
Q

What’s immune reconstitution inflammatory syndrome (IRIS)?

A

Paradoxical worsening of opportunistic infections e.g Cryptococcus after starting ART

May need to hold off on starting ART
Consider steroids

Immunology (6 decks)

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