IC18 HIV Flashcards
1
Q
What is the MEDIUM of transmission of HIV?
A
specific body fluids
* blood
* semen
* genital fluids
* breast milk
2
Q
What are the modes of transmission of HIV?
A
- unprotected sex with infected ppl
- sharing infected needles & syringes
- mother-to-child during pregnancy, childbirth, breastfeeding
- transfusion of contaminated blood & blood products
3
Q
In which population is it compulsory to screen for HIV in Singapore?
A
Pregnant women
4
Q
How do we diagnose HIV?
A
- seurm Ab detection HIV EIA test/Western blot
- HIV RNA detection with PCR
5
Q
What are the different stages of HIV?
A
- acute HIV infection
- asymptomatic
- persistent generalised lymphadenopathy
- AIDS
6
Q
Describe the first stage of HIV
A
Stage 1: Acute HIV infection
- flu-like symptoms with swollen lymph nodes, fever, malaise rash for 2-3 weeks
7
Q
Describe the second stage of HIV
A
Stage 2: Asymptomatic
- infected person may be asymptomatic for years
8
Q
Describe the third stage of HIV
A
Stage 3: Persistent generalized lymphadenopathy
unexplained lymph node enlargement in neck, underarm, groin for >3 months
9
Q
What is the definition of AIDS?
A
CD4 count < 200 cells/mm3
OR
presence of AIDS-defining diseases
10
Q
What are the surrogate markers for HIV therapy?
A
- CD4 count
- Viral load (HIV RNA)
11
Q
What is CD4 count an indicator of?
A
- immune function
- disease progression
- response to treatment
- when to initiate/discontinue prophylaxis for opportunistic infection
12
Q
What is the normal CD4 count?
A
500-1200 cells/mm3
13
Q
When do we measure CD4 count for a HIV infected person?
A
- baseline
- every 3-6 months after treatment initiation
- every 12 months after adequate response
14
Q
What is the definition of “adequate response” in HIV therapy?
A
Increase in CD4 count by 50-150 cells/mm3 in the first year of therapy
15
Q
What is an example of CD4 count being used to determine initiation/discontinuation of prophylaxis for opportunistic infections?
A
When CD4 < 200, initiate prophylaxis for pneumocystis pneumonia
16
Q
What is viral load an indicator of?
A
Response to HIV therapy
17
Q
When do we measure viral load for a HIV infected person?
A
- baseline before initiation of treatment
- 2-4 weeks after treatment initiation, max 8 weeks
- every 4-8 weeks until viral load suppression
- every 3-6 months/annually once stable + viral suppression
18
Q
What is our target viral load?
A
Undetectable HIV RNA levels (ie. viral suppression) by 8-24 weeks
19
Q
What are the goals of HIV therapy (ART)?
A
- reduce morbidity & mortality
- prolong duration & quality of survival
- restore & preserve immune function
- suppress HIV load for as long as possible
- prevent transmission
20
Q
When do we initiate ART for HIV infected persons?
A
ASAP regardless of CD4 count
21
Q
What are the benefits of early HIV treatment?
A
- maintain higher CD4 count & prevent potentially irreversible damage to immune system
- ↓ risk for complications
- ↓ risk of non-opportunistic conditions
- ↓ risk of transmission
22
Q
What are the limitations of early HIV treatment?
A
- expensive
- treatment fatigue
- S/E & toxicities of ART
- developing drug resistance
- transmission of drug resistant virus
- less time to prepare for ART (requires high adherence >95%)
23
Q
Describe the steps in the replication of HIV
A
- attachment to CD4 receptor
- binding to CCR5/CXCR4 co-receptors
- fusion
- reverse transcription
- integration
- transcription
- translation
- cleavage of polypeptides & assembly
- viral release
24
Q
Based on the steps in the replication of HIV, what are the targets of ART?
A
- Binding to CCR5/CXCR4 co-receptors
- Fusion
- Reverse transcription
- Integration
- Cleavage of polypeptide & assembly
25
What ART drug classes target the indicated steps?
2. Binding to CCR5/CXCR4 co-receptors
3. Fusion
4. Reverse transcription
5. Integration
8. Cleavage of polypeptide & assembly
Binding to CCR5 --> CCR5 antagonist
Fusion --> Fusion inhibitor
[Both considered entry inhibitors]
Reverse transcription --> Nucleoside & non-nucleoside reverse transcription inhibitors [NRTIs, NNRTIs]
Integration --> Integrase strand transfer inhibitor [INSTIs]
Cleavage of polypeptides & assembly --> Protease inhibitors [PIs]
26
What are the two recommended ART regimens for patients naive to ART?
1. 2 NRTI + 1 INSTI
1. 1 NRTI + 1 INSTI
27
What are the possible combinations for the first regimen?
Tenofovir/Emtricitabine/Bictegravir [TEB]
Tenofovir/Emtricitabine/Dolutegravir [TED]
Abacavir/Lamivudine/Dolutegravir [Triumeq] [ALD]
28
What are the possible combinations for the second regimen?
Emtricitabine/Dolutegravir [ED]
29
When is the second regimen of 1 NRTI + 1 INSTI contraindicted?
1. high HIV RNA count of > 500,000
2. HBV coinfection
3. initiating ART before HIV genotypic resistance testing & HBV testing results are available
30
What drugs belong to the nucleoside reverse transcriptase inhibitor [NRTIs] class?
TEZLA (heh)
* Tenofovir
* Emtricitabine
* Zidovudine
* Lamivudine
* Abacavir
31
What are the preparations of tenofovir available?
Tenofovir
* Alafanamide [TAF]
* Disoproxil fumarate [TDF]
32
What are the side effects of tenofovir?
* GI (N/V/D)
* renal impairment
* ↓ BMD (TAF < TDF)
33
What are the side effects of emtricitabine?
* minimal toxicity
* hyperpigmentation
* nausea, diarrhoea
34
What are the side effects of lamivudine?
* minimal toxicity
* GI (N/V/D)
35
What are the side effects of abacavir?
* GI (N/V/D)
* Hypersensitivity in genetically predisposed patients
* MI
36
Abacavir is contraindicated in what patient groups?
* high cardiovascular risk (due to concern of MI)
* patients positive for HLA-B*5701
37
What are the side effects of zidovudine?
* GI (N/V/D)
* myopathy
* bone marrow suppression
38
What toxicity concern is associated with NRTIs?
mitochondrial toxicity
39
Which drugs have a higher chance of causing the toxicity among all the NRTIs?
Z > T = A = L
40
What drugs belong to the integrase strand transfer inhibitors [INSTIs] class?
DERB (heh)
* Dolutegravir
* Elvitegravir
* Raltegravir
* Bictegravir
41
What are the general side effects of INSTIs?
* weight gain
* nausea, diarrhoea
* headache
* depression & suicidal thoughts in pts w preexisting psychiatric conditions
42
What is the unique side effect of bictegravir and dolutegravir?
↑ SCr due to ↓ tubular secretion of Cr, not due to declining kidney function
43
What are the unique side effects of raltegravir?
* pyrexia (causes fever)
* creatinine kinase elevation (risk of rhabdo)
44
What are the advantages of INSTIs?
* high genetic barrier to resistance (B, D > E, R)
* good virologic eeffectiveness (B, D)
* generally well tolerated
45
What are the disadvantages of INSTIs?
DDI
* polyvalent cations ↓ F
* CYP450 DDI
46
Why do INSTIs have CYP450 DDI?
D, E, B are 3A4 substrates
47
What drugs belong to the non-nucleoside reverse transcription inhibitors [NNRTIs] class?
ER
* Efavirenz
* Rilpivirine
48
What are the general side effects of NNRTIs?
* skin rash, SJS (E>R)
* QTc prolongation
49
What are the unique side effects of efavirenz?
* rash
* hyperlipidemia
* ↑ LDL-C & TG
* hepatotoxicity
* neuropsychiatric S/E (dizziness, depression, insomnia, abnormal dreams, hallucination)
50
What are the unique side effects of rilpivirine?
* depression
* headache
51
What drugs are contraindicated with rilpirivine and why?
PPI - higher gastric pH = ↓ oral F
52
What CYP enzymes is efavirenz metabolized by?
3A4
53
What CYP enzymes does efavirenz have an inducing effect on?
2B6
2C19
54
What CYP enzyme is rilpivirine metabolized by?
3A4
55
What are the advantages of NNRTIs?
* long half lives (OD dosing)
* less metabolic toxicities than some PIs
56
What are the disadvantages of NNRTIs?
* low genetic barrier to resistance
* cross-resistance
* CYP450 DDI
57
What drugs belong to the protease inhibitors [PIs] class?
drugs ending with 'vir'
* ritonavir
* darunavir
* lopinavir
* atazanavir
* fosamprenavir
58
What are the general side effects of PIs?
* GI (N/V/D)
* hepatic toxicity (esp w chronic hep B/C)
* fat maldistribution (lipohypertrophy)
* ↑ risk of osteopenia/osteoporosis
59
What are the unique side effects of ritonavir?
paresthesia ("pins & needles" feeling)
taste perversion
60
What are the unique side effects of atazanavir?
* hyperbilirubinemia
* QTc prolongation
* skin rash
61
What are the unique side effects of darunavir?
* skin rash
* SJS (as it is a sulfonamide)
62
What are the advantages of PIs?
* high genetic barrier to resistance
* resistance to PIs is less common
63
What are the disadvantages of PIs?
* metabolic complications
* CYP450 DDI
64
Why do PIs have CYP450 DDI?
ritonavir is a potent 3A4 + 2D6 inhibitor
65
What drug classes are considered entry inhibitors?
CCR5 antagonists
Fusion inhibitors
66
What drug belongs to the CCR5 antagonist class?
Maraviroc (Selzentry)
67
Who can use CCR5 antagonists?
in patients whose HIV strain is CCR5 predominant
68
What test is needed to determine that?
co-receptor tropism essay
69
What hepatic enzyme metabolizes maraviroc?
3A4
70
What are the side effects of maraviroc?
* abdominal pain
* cough
* dizziness
* musculoskeletal symptoms
* pyrexia
* rash
* URTI
* hepatotoxicity
* orthostatic hypotension
71
What drug is in the fusion inhibitors class?
Enfuvirtide
72
What are the side effects of enfuvirtide?
* injection site reactions (erythema/induration, nodules/cysts, pruritus, ecchymosis)
* bacterial pneumonia
* hypersensitivity (rare)
