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PR3124 PT3 > HIV & AIDS > Flashcards

HIV & AIDS Flashcards

1
Q

Which group of the retrovirus family does HIV belong to?

A

Lentivirus

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2
Q

Which specific target cell in the immune system does HIV attack & destroy?

A

CD4 T-helper cells

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3
Q

Describe the mode of transmission for HIV.

A

Through specific body fluids - blood, semen, genital fluids & breast milk:

1) Unprotected sexual intercourse (98% of new cases in SG)
2) Sharing infected syringes & needles (between IV drug users)
3) Vertical / Mother-to-child transmission during pregnancy, child-bearing or through breastfeeding
4) Contaminated blood & blood products

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4
Q

Which specific populations should be screened preemptively for HIV?

A
  • IV drug users
  • Individuals who have unprotected sex w/ multiple partners
  • MSM
  • Prostitution / Commercial sex workers
  • Pt w/ STDs
  • Recipients of multiple blood transfusions
  • Individuals who have been sexually assaulted
  • Pregnant women (mandatory in SG)
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5
Q

How is HIV diagnosed in a suspected patient?

A

1) Serum Ab detection
- HIV EIA (enzyme immunoassay) Ab tests
- Western blot
2) HIV RNA detection / quantification (Viral load)
- PCR amplification of HIV

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6
Q

Describe the clinical presentation of an HIV pt.

A

1) Acute/Primary:
- Occurs soon after contracting HIV
- Flu-like symptoms (fever, malaise & rash) w/ swollen lymph nodes x 2-3 weeks
2) Asymptomatic/Latent: persists for many years
3) Persistent Generalised Lymphadenopathy:
- Persistent unexplained lymph node enlargement in neck, underarms & groin for > 3 months
4) AIDS:
- Defined as CD4 < 200 cells/mm3 or presence of AIDS-defining diseases
- Advanced stage of HIV infection; pt succumbs to infections by 1 of 26 unusual organisms that uninfected person can resist
- Involve lung, eyes, GIT, nervous system & skin
- Systemic smx like fevers, unexplained weight loss & diarrhea are common
- Rare cancer (e.g. Non-Hodgkin’s lymphoma & Kaposi sarcoma) may be found
- Pneumocystis pneumonia is a possible complication

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7
Q

What are the primary therapeutic goals of antiretroviral therapy?

A

Reduced HIV-associated morbidity & mortality
Prolong duration & quality of survival
Restore & preserve immunologic function
Maximally & durably suppress plasma HIV infection
Prevent HIV transmission

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8
Q

Which laboratory markers are used as surrogate markers in the management of HIV patients on antiretroviral therapy (ART)? How are they used to monitor HIV patients on antiretroviral therapy?

A

1) CD4 T-lymphocyte Count
- Healthy CD4 count = 500-1200 cells/mm^3
- Most important lab indicator of immune fx in HIV pt.
- Strongest predictor of subsequent disease progression & survival (prognosis)
- Used to assess response to ART
- Assessed at baseline & q 3-6 months after Tx initiation, q 12 months after adequate response
- Adequate CD4 response = increase in CD4 of 50-150 cells/mm^3 during 1st year of Tx
- Used to assess need to initiate or discontinue prophylaxis for opportunistic infections (upon hitting certain thresholds)
- e.g. prophylaxis for pneumocystis pneumonia starts when CD4 < 200 cells/mm3

2) Viral Load (via PCR)
- Most important indicator of response to ART & useful in predicting clinical progression
- Measured before Tx initiation & w/in 2-4 weeks (no later than 8 weeks) after Tx initiation or modification; thereafter, q 4-8 weeks until viral load is suppressed
- Effective regimen generally achieve viral suppression (i.e undetectable HIV RNA load) in 8-24 weeks
- Pt on stable regimen & suppressed viral load to be monitored q 3-6 months (can be up to q 1 yr)

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9
Q

Under what conditions will it be considered as an adequate therapeutic response in HIV pt on ART?

A

Increase in CD4 of 50-150 cells/mm3 during 1st year of Tx
AND
Undetectable HIV RNA load in 8-24 weeks

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10
Q

When should we recommend initiating antiretroviral therapy (ART) to HIV pt?

A

Recommend regardless of CD4 count to ALL HIV-infected pt to reduce HIV-associated morbidity & mortality, as well as to prevent HIV transmission.
Important to educate on the benefits & considerations of ART, and address strategies to optimise adherence.
[Case-by-case] ART may be deferred due to clinical / psychological factors, BUT Tx should be initiated ASAP.

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11
Q

What are some benefits of earlier initiation of ART for HIV pt?

A
  • Maintenance of higher CD4 count & prevention of potentially irreversible damage to immune system,
  • Decrease risk of HIV-associated complications when CD4 > 350 cells/mm3, including TB, Non-Hodgkin’s lymphoma, Kaposi sarcoma, peripheral neuropathy & HIV-associated cognitive impairment
  • Decrease risk of opportunistic conditions, including CVD, CKD, liver disease & non-AIDS-associated malignancies & infections
  • Decrease risk of HIV transmission to others
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12
Q

What are some limitations of earlier initiation of ART for HIV pt?

A
  • Development of Tx-related SE & toxicities (less observed w/ newer agents)
  • Development of drug resistance due to incomplete viral suppression, resulting in loss of future Tx options
  • Transmission of drug-resistant HIV in pt w/o full virologic suppression maintenance (including HIV-naive pt.)
  • Less time to learn about HIV & its treatment & less time to prepare for the need of adherence to Tx
  • Increased total time on medication & greater chance of Tx fatigue subsequently
  • Increased cost
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13
Q

What are some factors to consider when selecting an initial ART regimen for HIV pt?

A

Regimen selection should be individualised based on:

  • Pt. understanding of HIV
  • Cost & availability
  • Adherence issues & convenience (less concerning for newer agents) such as pill burden, dosing frequency & food & fluid considerations
  • Virological efficacy
  • Potential adverse effects (comorbidities, DDI)
  • Childbearing potential
  • Genotypic drug resistance testing
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14
Q

List all the drug classes available in the ART armamentarium against HIV.

A

Backbone Regimen (2 NRTIs + 1 INSTI):

1) Nucleoside Reverse Transcriptase Inhibitor (NRTI) (-ovir, -avir, -udine, -abine)
2) Integrase Strand Transfer Inhibitor (INSTI) (-gravir)

Alternatives:

3) Non-Nucleoside Reverse Transcriptase Inhibitor (NNRTI) (-virine, -virenz)
4) Protease Inhibitor (PI) (-navir)
5) Fusion Inhibitor
6) Entry Inhibitor (CXCR4/CCR5 Antagonists)

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15
Q

What is the mechanism of action of NRTIs & NNRTIs?

A

Inhibit viral reverse transcriptase that converts viral ssRNA to ssDNA to dsDNA

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16
Q

What is the mechanism of action of INSTIs?

A

Block viral integrase from integrating viral dsDNA into host dsDNA

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17
Q

What is the mechanism of action of entry inhibitors?

A

Blocks HIV from access to the CXCR4/CCR5 co-receptor and prevents the fusion process of HIV to CD4 T-lymphocytes

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18
Q

What is the mechanism of action of fusion inhibitors?

A

Inhibits fusion of the viral envelope with the host cell membrane of CD4 T-lymphocytes

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19
Q

What is the mechanism of action of protease inhibitors?

A

Inhibits viral maturation process, resulting in lack of functional virion formation

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20
Q

What is the recommended first-line ART for HIV-naive pt w/o Hepatitis B co-infection (i.e. first-time Tx)?

A

2 NRTIs + 1 INSTI: (either/or)

1) Tenofovir + Emtricitabine + Bictegravir
2) Tenofovir + Emtricitabine + Dolutegravir
3) Abacavir + Lamivudine + Dolutegravir

Alternatively, 1 NRTI + 1 INSTI:
1) Emtricitabine + Dolutegravir

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21
Q

What is the recommended first-line ART for HIV-naive pt w/ Hepatitis B co-infection (i.e. first-time Tx)?

A

2 NRTIs + 1 INSTI: (either/or)

1) Tenofovir + Emtricitabine + Bictegravir
2) Tenofovir + Emtricitabine + Dolutegravir

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22
Q

Emtricitabine + Dolutegravir can be recommended as a first-line ART for an HIV-naive pt who has a Hepatitis B co-infection. True or false?

A

False!!
1 NRTI + 1 INSTI should NOT be recommended for pt:
1) w/ HIV RNA > 500,000 copies/mL,
2) w/ HBV co-infection, or
3) w/o results of HIV genotypic resistance testing or HBV results

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23
Q

Abacavir + Lamivudine + Dolutegravir cannot be recommended as a first-line ART for an HIV-naive pt who has a Hepatitis B co-infection. True or false?

A

True.
Two anti-HBV drugs MUST be used for HBV co-infection with HIV as first-line ART. However, ONLY tenofovir, emtricitabine & lamivudine has activity against HBV. Thus, w/ only lamivudine having anti-HBV activity, such a combination should NOT be recommended to HIV-naive pt w/ hepatitis B.

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24
Q

In the event of Tx failure of ART, which drug class(es) should be swapped out?

A

INSTIs should be swapped out for either NNSTIs or boosted PIs.
In severe resistance, entry & fusion inhibitors are used over INSTIs.

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25
Q

Which particular drugs in the ART armamentarium are used as pharmacokinetics enhancers for PIs?

A

Ritonavir (/r) & cobicistat (/c)
- CYP3A4 inhibitors included in the formulation of ART to increase concentrations of various antiretroviral drugs (esp. PIs & elvitegravir [INSTI])

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26
Q

Name some examples of NRTIs.

A

Tenofovir, Emtricitabine, Abacavir, Lamivudine, Zidovudine

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27
Q

Name some examples of NNRTIs.

A

Efavirenz, Rilpivirine

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28
Q

Name some examples of INSTIs.

A

Bictegravir, Dolutegravir, Raltegravir, Elvitegravir

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29
Q

Name an example of an entry inhibitor.

A

Maraviroc

30
Q

Name an example of a fusion inhibitor.

A

Enfuvirtide

31
Q

Name some examples of PIs.

A

Ritonavir, Lopinavir, Darunavir, Atazanavir, Fosamprenavir (co-formulated w/ ritonavir or cobicistat)

32
Q

How are NRTIs eliminated?

A

Renal clearance

33
Q

Which NRTI is used for the treatment of pregnant HIV pt?

A

Zidovudine

34
Q

Which NRTI does not require renal dose adjustment in HIV pt with renal impairment?

A

Abacavir

35
Q

What are some of the common side effects of NRTIs?

A

Minimal DDI
Common: Nausea, vomiting (except emtricitabine) & diarrhea
Rare but serious SE related to mitochondrial toxicity:
- Lactic acidosis & hepatic steatosis (fatty infiltrate)
- Lipotrophy (Zidovudine > Tenofovir = Abacavir = Lamivudine)

36
Q

Which NRTI has the highest risk of causing lipoatrophy as a side effect?

A

Zidovudine

37
Q

Which antiretroviral drugs amongst the NRTIs are reported to have minimal toxicities?

A

Emtricitabine & Lamivudine

38
Q

Which particular NRTI requires prior testing to the presence of HLA-B*5701 gene in HIV pt before its initiation?

A

Abacavir

39
Q

Which NRTI can cause hyperpigmentation as a potential side effect?

A

Emtricitabine

40
Q

Which NRTI can cause renal impairment as a potential side effect?

A

Tenofovir

41
Q

Abacavir + Lamivudine + Dolutegravir can be recommended as a first-line ART for an HIV-naive pt who expresses the HLA-B*5701 gene. True or false?

A

False!
Abacavir should NOT be given to patients who expresses the HLA-B*5701 gene due to hypersensitivity reactions that can be fatal (i.e. anaphalyxis). Do NOT rechallenge!

42
Q

Which NRTI is associated with myocardial infarction & should not be used in HIV pt w/ cardiovascular risk?

A

Abacavir

43
Q

Which NRTI has been associated with myopathy as a potential side effect?

A

Zidovudine

44
Q

Which NRTI is associated with bone marrow suppression as a potential side effect?

A

Zidovudine

45
Q

Rank the INSTIs from the highest to the lowest genetic barrier to resistance.

A

Bictegravir = Dolutegravir > Raltegravir = Elvitegravir

46
Q

What are some of the common side effects of INSTIs?

A 
Generally well tolerated
Common SE: 
- Nausea & diarrhea
- Weight gain
- Headache
Rare: (esp. w/ preexisting psychiatric conditions)
- Depression & suicidality
47
Q

What are some DDIs faced when using INSTIs as part of ART?

A

Bioavailability lowered by concurrent administration of polyvalent cations (e.g. antacids, Fe supplements)
CYP3A4 substrates: Bictegravir, Dolutegravir & Elvitegravir

48
Q

Which INSTI is NOT metabolised by CYP3A4?

A

Raltegravir

49
Q

Which INSTI(s) may result in an increase in serum creatinine due to inhibition of renal tubular secretion?

A

Bictegravir & Dolutegravir

50
Q

Which INSTI is associated with drug fever (pyrexia)?

A

Raltegravir

51
Q

Which INSTI has been associated with rhabdomyolysis?

A

Raltegravir

52
Q

Which INSTIs are associated with good virologic effectiveness?

A

Bictegravir & Dolutegravir

53
Q

What are some common side effects of NNRTIs?

A

Hypersensitivity (skin rash & Stevens-Johnson Syndrome)
QTc prolongation
Hyperlipdemia: increase in LDL-C & TG
Neuropsychiatric SE: HA, depression, dizziness, insomnia, hallucination

54
Q

What are the advantages & disadvantages of using NNRTIs as part of ART for HIV pt.?

A

(+) Long half-lives & less metabolic toxicity (hyperlipidemia, insulin resistance) than some PIs
(-) Low genetic barrier to resistance than NRTIs, presence of cross-resistance among approved NNRTIs & potential for mixed CYP450 interactions (i.e. inhibition & induction)

55
Q

Which NNRTI is contraindicated in pt receiving ART while on concomitant PPI for peptic ulcer disease?

A

Rilpivirine

56
Q

What are the advantages & disadvantages of using PIs as part of ART for HIV pt.?

A

(+) High genetic barrier to resistance & PI resistance is less common
(-):
- Metabolic complications (dyslipidemia, insulin resistance)
- GI SE (N/V/D)
- Heptatotoxic (esp w/ chronic heptatitis B & C)
- CYP3A4 inhibitors & inducers; DDI potential
- Fat maldistribution (Lipohypertrophy & buffalo humps)
- Increased risk to osteopenia/osteroporosis

57
Q

Which NNRTI is associated with hepatotoxicity as a potential side effect?

A

Efavirenz

58
Q

Which formulation of tenofovir has a better toxicological profile (i.e. safer)?

A

Tenofovir alafenamide (TAF) is safer than Tenofovir disoproxil fumarate (TDF)

59
Q

Which PI is contraindicated in pt receiving ART while on concomitant PPI for peptic ulcer disease?

A

Atazanavir

60
Q

Which PIs have generally good GI tolerability w/ less lipid SE?

A

Darunavir & Atanazavir

61
Q

Which PI has been associated with paresthesia (numbness of extremities)?

A

Ritonavir

62
Q

Which PI has been associated with potential Stevens-Johnson Syndrome as a rare side effect?

A

Darunavir (sulfonamide formulation)

63
Q

Which PI has been associated with QTc prolongation?

A

Atazanavir

64
Q

How is enfuvirtide administered?

A

SC injection BD

65
Q

What are some side effects associated with the use of enfuvirtide?

A

Injection site reaction, hypersensitivity (rare), increased bacterial pneumonia

66
Q

Under what conditions should maraviroc be used for the Tx of HIV pt?

A

ONLY pt whose HIV strain uses the CCR5 receptor to enter CD4 cells can use maraviroc

  • Need co-receptor tropism assay before initiation; MUST be CCR5 predominant to use maraviroc
  • NOT to use if CXCR4 predominant or dual/mixed tropism
67
Q

What are some side effects associated with the use of maraviroc?

A 
[DU CAMPHOR]
Dizziness
URTI
Cough
Abdominal pain
Musculoskeletal symptoms
Pyrexia
Hepatotoxicity
Orthostatic hypotension
Rash
68
Q

Maraviroc is a CYP2D6 substrate. True or false?

A

False. Maraviroc is a CYP3A4 substrate.

69
Q

What are some reasons for Tx failure of ART?

A 
Patient:
- Adherence < 95%
- Dosing schedule & requirements
- Provider experience
Drug:
- Drug toxicities 
- DDI
Virus:
- Viral resistance
70
Q

What are some strategies that can be counselled to HIV pt. to improve adherence to ART?

A
  • Establish readiness to start therapy
  • Provide education on medication dosing
  • Review, anticipate & treat side effects
  • Utilise educational aids including pictures, pillboxes & calendars
  • Engage family & friends for support
  • Simplify regimens, dosing & food requirements (taking antiretrovirals w/ or w/o food
  • Utilise team approach w/ nurses, pharmacists & peer counsellors
  • Provide accessible, trusting healthcare team

PR3124 PT3 (12 decks)

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