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Infectious Diseases > HIV > Flashcards

HIV Flashcards

1
Q

Cause of HIV

A

Caused by HIV-1 and HIV-2 (retroviruses)

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2
Q

4 groups of HIV-1 and prevalence worldwide

A

Groups: M, N, O and P

HIV-1 group M viruses are responsible for the global HIV pandemic. Have 9 subtypes: A-D, F-H, J and K

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3
Q

Which HIV-1 subtype is predominant in Australia?

A

HIV-1 subtype B (also in America, Western Europe)

subtype C in Africa and India

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4
Q

Where are infections by HIV-2 seen?

A

Largely confined to West Africa

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5
Q

Most severely HIV-affected region of the world

A

Sub-Saharan Africa

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6
Q

Basic pathophysiology of HIV infection

A
  1. HIV targets & infects CD4+ T-lymphocytes with its primary receptor CD4 and a co-receptor (CCR5 or CXCR4)
  2. Virus-encoded reverse transcriptase coverts viral RNA genome into HIV DNA
  3. HIV DNA is transported to the cell nucleus, where virus encoded integrase incoporates HIV DNA into the cell’s DNA
  4. Once integrated into the host genome, HIV genetic elements are transcribed into mRNA –> HIV proteins (long chains)
  5. New HIV virions assemble
  6. The HIV virions bud from the cell wall. HIV proteases digest the long chains, which makes the new virions infectious
  7. New HIV virions target the next CD4 cell

Each step above can be targeted by antiretroviral medications

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7
Q

Routes of HIV transmission (3)

A
  1. Direct sexual contact (semen, vaginal fluid, blood)
  2. Perinatal transmission
  3. Direct contact with infected blood (occupational, needle sharing)
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8
Q

Risk factors for HIV transmission
From highest risk to lowest risk

And what disease factor does transmission risk highly depend on?

A

HIGHLY dependent on the viral load present in the fluid that one is exposed to.

Risk factors:

  • Contaminated blood products (back in the day)
  • Perinatal transmission without intervention (20% risk)
  • Receptive anal intercourse (1.4% per exposure)
  • Needle sharing with HIV infected person (0.6% per exposure)
  • Occupational needle stick (0.2% per exposure)
  • Receptive penile-vaginal intercourse (0.1% per exposure)
  • Oral intercourse: low, but not zero
  • Biting, spitting, exposure of intact skin (negligible)
  • Exposure to fluids from an individual who is HIV infected but undetectable (0% risk)
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9
Q

Clinical presentation

- Acute antiretroviral syndrome

A

Antiretroviral syndrome (mimics EBV)

  • Prolonged fever
  • Fatigue
  • Cervical adenopathy
  • Myalgias
  • Arthralgias
  • Pharyngitis

When it occurs, painful mucocutaneous ulcerations are one of the most distinctive manifestations of acute HIV infection

Some patients may have no or very mild sx only

May present with aseptic meningitis

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10
Q

Clinical presentation:

  • Early infection (first 6 months)
  • Chronic HIV infection (6mo - >10 years)
A 
Early infection (acute infection with seroconversion):
Asymptomatic, vague, non-specific complaints

Chronic HIV infection:

  • Most are asymptomatic
  • Sometimes generalised lymphadenopathy
  • Mucosal candidiasis common when immune function deteriorates
  • Reactivation of VZV –> shingles
  • Oral hairy leukoplakia
  • Immune-mediated TCP
  • Weight loss
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11
Q

Clinical presentation:

- Advanced HIV and AIDS

A
  • Recurrent and stubborn opportunistic infections

- Anorexia with wasting

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12
Q

Prognosis for patients with CD4+ T lymphocyte count <50 (untreated)

A

Survival average of <18 months

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13
Q

AIDS defining conditions - partial list (13)

A

Sustained CD4+ TL count of <0.2x10^9/L (<200/uL)

Multiple or recurrent bacterial infections (children <6)

Recurrent pneumonia (>6)

Candidiasis extending beyond the orophraynx to oesophagus/respiratory tract

CMV disease beyond liver, spleen, LNs

HSV infection of oesophagus or respiratory tract

Disseminated infection of non-TB mycobacterium

Kaposi sarcoma

Burkitt or immunoblastic lymphoma

Primary lymphoma of the brain

Pneumocystis jirovecii pneumonia

Progressive multifocal keukoencephalopathy

Toxoplasmosis of the brain

Wasting syndrome

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14
Q

Diagnostic tests for HIV when diagnosis is suspected (i.e. not screening)

  • 2 x tests
  • Outcomes of these tests and further steps
A
  1. HIV immunoassay (tests for HIV p24 antigen AND anti-HIV antibody). Detects >15 days post exposure. Better than antibody only, as antigen can be detected earlier on.

In addition to:

  1. HIV viral load (quantitative HIV RNA PCR). Detects >5 days post exposure.

The approximate timing of infection can be assessed by the pattern of test results.

Possible outcomes:
A. Negative HIV immunoassay and viral load: HIV infection has not been acquired. Repeat in 2/52 if suspicious

B. Negative HIV immunoassay and positive viral load: usually suggests early infection.

Repeat positive viral load test supports infection. Repeat serology as well in a few weeks to document seroconversion.

Positive serology doesn’t necessarily rule out very recent infection, given serology is now super sensitive (some patients seroconvert within 6 months on modern tests). Consider clinical presentation (i.e. exposure history, recent acute RV syndrome, very high RNA levels) to infer actual timeframe.

A viral load of <1000 copies/mL may be a false positive. Must immediately repeat this.

C. Positive serology and viral load. Next step –> confirmatory HIV-1/2 antibody differentiation assay. If not available in lab, use Western blot.

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15
Q

What test to perform in infants of HIV-infected mothers for diagnosis?

A

Infants will test HIV seropositive due to presence of transplacental maternal antibodies. Therefore can’t use tests that rely on antibody detection (i.e. 4th gen assay) until maternal antibody clears. HIV assays are so sensitive that this may take up to 15 months.

Therefore, the preferred test for infants is qualitative RNA PCR assay.

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16
Q

Viral RNA level and CD4 count in:

A. Early HIV infection
B. Chronic HIV infection

A

A. Acute infection = 6 month period post seroconversion

  • Viral RNA level usually VERY high (>100,000 copies/mL. Peak is usually at time of seroconversion, usually stabilises by 6 months. This is when HIV-specific CD8+ T cells emerge
  • CD4 count can drop transiently in early infection (but opportunistic infections rare)

B. Stable viral RNA levels with progressive decline in CD4 cell count. The rate of CD4 decline is associated with level of viraemia.

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17
Q

Ddx for acute HIV infection

A

EBV, CMV, toxoplasmosis, rubella, syphilis, viral hepatitis, disseminated gonococcal infection, other viral infections

Consider autoimmune diseases

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18
Q

HIV screening in general population - diagnostic tests

A
  1. Fourth generation HIV immunoassay (our regular antigen/antibody test)

THEN, if positive:

  1. Perform a HIV-1/HIV-2 antibody differentiation immunoassay

This will inform you of a subtype of HIV. If negative or indeterminate (i.e. not consistent with the initial immunoassay):

  1. Perform HIV RNA PCR (viral load)
    If positive, acute HIV-1 infection
    If negative, negative for HIV-1
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19
Q

A patient is diagnosed with acute HIV… what investigation should be done next? And what counselling should be given?

A

Drug resistance testing
20% of newly infected patients have HIV with at least one drug resistance mutation.

Refer to specialist for commencement of therapy. Therapy should not wait for the results of drug resistance testing.

Counselling:
Compliance with medication
Condom use
Avoid sharing needles

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20
Q

Why do HIV patients develop comorbid conditions i.e. CVD, renal disease, OP, cognitive dysfunction & certain malignancies, younger than the general population?

A

Thought to be due to chronic inflammation, immune activation or immunosenescence

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21
Q

AIDS definition

A

Acquired immunodeficiency syndrome

Defined by CD4 cell count <200cells/microL or the presence of any AIDS defining conditions

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22
Q

Progression from HIV –> AIDS without ART

A

Usually gradual over 5-10 years without treatment

Some patients are ‘HIV controllers’ and manage > 10 years (low viral loads, stable CD4)

Some patients are rapid and transition within 1-2 years

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23
Q

Physiological markers of effective ART

A
  1. Sustained suppression of HIV RNA
  2. Improved immunity (CD4 counts)
  3. Reduced HIV immune activation (proinflam cytokines, chronic inflammation, T cell activation)
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24
Q

Prognosis of HIV with ART

A

Life expectancy for a person with HIV with virologic suppression on ART approaches that of the general population (provided ART started early with acceptable CD4 count)

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25
Q

Factors that correlate with reduced CD4 recovery once starting ART

A

Older age
Male sex
Comorbidities e.g. HCV

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26
Q

Strategies for infection prevention in HIV positive patients

A
  1. Restore cellular immunity with ART
  2. Immunisations: s. pneumonia, HBV (less effective in advanced disease - may wait until CD4 counts have recovered a little)

ADDITIONAL strategies are needed for those with significant immunosuppression (e.g. not on ART for various reasons)

  1. Avoid exposures (cats for toxoplasma, undercooked meats for bartonella and fungi), etc.
  2. Antimicrobial therapies in conjunction with starting ART
27
Q

In which situations are antimicrobials prescribed to asymptomatic patients with HIV?

And at what CD4 count should we administer these medications?

A

Aims to prevent opportunistic infections. Is usually based on CD4 count.

  1. To prevent infection in uninfected individuals e.g. PJP (CD4 <200), MAC <50
  2. To prevent active infection by dormant pathogens in the body .e.g Toxoplasma (CD4 <100), TB (always if latent)
  3. Pre-emptive therapy in patients who serologically have an infection, but remain asymptomatic for now (.e.g. coccidiodomycosis - CD4 < 250 and cryptococcal CD4 <100)
28
Q

Initial evaluation of a patient with HIV - goals (4)

A
  1. Assess stage of HIV disease
  2. Determine risk for other infections
  3. Identify comorbidities that are associated with infection or relevant to treatment
  4. Select an ART regimen
29
Q

Initial history from HIV positive patient… don’t forget:

A

Hx of exposure
Prior treatment history
Common or important comorbidities (hepatitis, STIs, TB, CVD)

Assess understanding of illness and issues of transmission

30
Q

Initial labs from a HIV positive patient

A
  • Staging parameters: CD4 count, HIV RNA, HIV genotype testing
  • Baseline organ function
  • Screen for potential co-infections: hepatitis, TB, STIs, including HPV-related neoplasia
31
Q

HIV-2

Differences cf. HIV-1 and treatment implications

A

Slower immunologic decline, but once CD4 <200, similar high risk profile.

HIV-2 has intrinsic resistance to entire classes of ART e.g. NNRTIs and fusion inhibitors.

Usually treated with 2 x NRTIs + protease inhibitor

Can’t test for drug resistance in HIV-2.

32
Q

What are the three most common bacterial causes of pneumonia in HIV patients?

A

Strep pneumoniae
H influenzae
Staph aureus

Consider ddx TB and PJP
Consider prophylactic antis usually taken when deciding rx

33
Q

PrEP treatment regimen

A

For patients at medium and high risk of HIV infection (see eTG guidelines)

Tenofovir disoproxil fumarate + emtricitabine 300mg + 200mg PO daily

OR

tenofovir disoproxil maleate + emtricitabine

OR

tenofovir disoproxil phosphate + emtricitabine

34
Q

Classes of ART

A

Nucleoside/nucleotide reverse transcriptase inhibitors (NRTIs)

Non-nucleoside reverse transcriptase inhibitors (NNRTIs)

Protease inhibitors

Integrase strand transfer inhibitors (INSTIs)

Fusion inhibitors

Entry inhibitors

35
Q

What are cobicistat and ritonavir?

A

Boosting drugs
Cytochrome p450 inhibitors that are used to increase plasma concentrations of PIs and elvitegravir (integrase inhibitors)

36
Q

Initial and maintenance treatment of HIV - number of drugs

A

Need 3 x antiretrovirals for initial therapy

Once viral suppression achieved, some patients can change to a 2 drug regimen

37
Q

Examples of NRTIs

A 
Abacavir!!!!
Emtricitabine !!!!
Lamivudine !!!
Tenofovir alafenamide and the tenofovir disoproxils !!!
Zidovudine
38
Q

Examples of NNRTIs

A

Etravirine
Nevirapine
Rilpivirine

39
Q

Examples of protease inhibitors

A 
Atazanavir 
Darunavir !!!
Fosamprenavir 
Indinavir 
Lopinavir 
Ritonavir 
Saquinavir 
Tipranavir
40
Q

Examples of integrase inhibitors

A

Bictegravir
Dolutegravir
Elvitegravir
Raltegravir

(BRED)

41
Q

Examples of fusion inhibitors

A

Enfuvirtide

42
Q

Entry inhibitors

A

Maraviroc

43
Q

Single-tablet once daily combination products containing 3 x ARV drugs: NRTI + INSTI products

A
  1. Biktarvy: tenefovir alafenamide + emtricitabine + bictegravir
  2. Genvoya: tenefovir alafenamide + emtricitabine + elvitegravir + cobicistat
  3. Triumeq: dolutegravir+abacavir+lamivudine
    (4. Stribild: tenofovir disoproxil fumarate+emtricitabine+elvitegravir+cobicistat)
44
Q

Single-tablet once daily combination products containing 3 x ARV drugs: NRTI + NNRTI products

A
  1. Atripla: tenofovir disoproxil fumarate+emtricitabine+efavirenz
  2. Eviplera: tenofovir disoproxil fumarate+emtricitabine+rilpivirine
  3. Odefsey: emtricitabine+rilpivirine+tenofovir alafenamide
45
Q

MOA of most combination tablets with two ARV drugs

A

Either dual NRTIs or PI plus cobicistat

46
Q

First line initial HIV therapy - drug class combinations

A

2 x NRTIs + INSTI

First line drugs are:

  • Triumeq
  • Biktarvy
  • Genvoya (also has cobicistat)

If the above are ineffective, try:
Descovy + dolutegravir
OR
Descovy + raltegravir

47
Q

If first line initial HIV therapy (2 x NRTIs + INSTI) is not suitable, which classes do we go for?

A

NRTI x 2 + NNRTI
Or
NRTI x 2 + Protease inhibitors

48
Q

Which regimen to use in HIV and HepBV coinfection?

A

Biktarvy or Genvoya — emtricitabine also treats HepB

49
Q

What test to do before prescribing abacavir?

A

HLA-b*5701 allele

- Highly predictive of hypertensitivity (can be fatal)

50
Q

Tests for toxicity of ART

A

FBE, UEC, Cr, LFTs

51
Q

ART drugs that affect Creatinine secretion (e.g. elevate serum Cr but do not affect renal function)

A

BAD FOR CR (BDCR)
Bictegravir, dolutegravir, cobicistat, rilpivirine

Recheck Cr 4/52 after starting

52
Q

What to monitor specifically for tenofovir?

A

KIDNEY FUNCTION!

Check Cr, urine PCR, glycosuria, serum phosphate every 3/12 for first year, then 6-12/12 thereafter

53
Q

What is the serious ocular complication of AIDS?

  • Risk factors
  • Clinical features
  • Most serious complication
  • Diagnosis
  • Worsening vision post treatment of this OI with recent ART commencement?
A

CMV retinitis

Risk factors: CD4 count < 50, PHx OIs, high viral load, CMV viraemia

Clinical features: blurring, loss of central vision, scotomas & floaters

Most serious cx: retinal detachment with complete visual loss

Diagnosis: MUST be diagnosed by ophthal. Labs for CMV DNA PCR, antigen, culture are not helpful; negative results do not rule out CMV retinitis.

  • If worsening vision after rx with valganciclovir (and have recently commenced ART), consider progession of CMV vs IRIS. Requires ophthal review.
54
Q

What is IRIS? What % of patients does it occur in?

A

Immune reconstitution inflammatory syndrome
- Paradoxical worsening/unmasking of pre-existing subclinical infections, or those which have already been treated, as the immune system recovers with ART

<30% of patients (incidence may be much lower than this)

55
Q

What two factors do the likelihood and severity of IRIS depend on?

A
  • Extent of CD4 T cell immune suppression prior to ART (<100, higher risk)
  • The degree of viral suppression/immune recovery following initiation of ART (good response)
56
Q

Leading pathogens associated with IRIS

A
  • M. tuberculosis
  • MAC
  • CMV
  • Cryptococcus
  • Pneumocystis jirovecii
  • HSV
  • Hep BV
  • HHV8 (assoc w Kaposi sarcoma)
57
Q

Typical pattern of CD4+ T cell recovery following initiation of ART

A

Biphasic pattern.

There is a rapid increase in CD4 count in first 3-6 months (memory T cells), then a slower increase in naive CD4 cells.

58
Q

When should you start ART if a patient has an OI?

Are there any exceptions?

A

Wait 2/52 after treating post OIs
Exceptions: cryptococcal and TB meningitis. Risks of possible serious IRIS outweigh benefits of ART –> must wait longer before starting ART

59
Q

What do we use valganciclovir for?

What are its associated toxicities?

A

Treatment & prophylaxis of CMV!

Toxicities:

  • Bone marrow suppression! Particularly leukopenia
  • Renal insufficiency

Note that co-administration with Bactrim (which can also be myelosuppressive and nephrotoxic) can be problematic.

60
Q

Prophylaxis for MAC

A

azithromycin

61
Q

Prophylaxis for CMV retinitis

A

No prophylaxis

62
Q

Three conditions that can occur at any CD4 count

A

TB
PML
Kaposi sarcoma

63
Q

Normal CD4 counts

CD4 count at which you start to get worried about OIs

A

Normal counts 800-1000
<400, increased risk of OIs
< 200, severely increased risk (e.g. AIDS)

Infectious Diseases (13 decks)

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