HIV Flashcards

1
Q

Mode of transmission for HIV

A

Body fluids: blood, semen, genital fluids, and breast milk

  • Unprotected sex with infected person
  • Sharing infected syringes/needles
  • Mother-to-child: pregnancy, at birth, breastfeeding
  • Transfusion with contaminated blood (products)
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2
Q

Why is there little mother-to-child transmission of HIV now?

A

Mandatory screening of all pregnant women since 2008

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3
Q

Who should be tested for HIV?

A
  • IV drug users
  • Person who have unprotected sex with multiple partners
  • Man who have sex with man
  • Commercial sex workers
  • Persons treated for STDs
  • Persons who have been sexually assaulted
    Rare as there is screening:
  • Pregnant women
  • Recipients of multiple blood transfusion
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4
Q

Diagnostic tests for HIV infection

A
  1. Serum antibody detection
    - HIV EIA (enzyme immunoassay antibody) tests
    - Western blot
  2. HIV RNA detection (viral load)
    - nucleic acid amplification (PCR)
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5
Q

What are the goals of antiretroviral therapy?

A
  • reduce morbidity & mortality
  • prolong duration and quality of survival
  • restore and preserve immunologic function
  • maximally & durably suppress viral load to undetectable levels
  • prevent HIV transmission
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6
Q

What is CD4 count used as a marker for?

A

Indicator of immune function and predictor of disease progression & survival

  1. Response to ART
    - Monitor: baseline, every 3-6mo after initiation, every 12mo after adequate response
    - Adequate response: increase CD4 by 50-150 cells/mm3 in 1st year of therapy
  2. Initiate/discontinue prophylaxis for opportunistic infx
    - e.g. PCP prophylaxis started when CD4 <200 cells/mm3
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7
Q

What does viral load indicate? How should we monitor viral load?

A

Response to ART

  • Monitor: baseline, 2-4wk (max 8 wk) after initiation or modification, every 4-8wk until suppressed
  • Effective ART: viral suppression by 8-24wk
  • Monitor every 3-6mo (stable regimen + suppressed viral load)
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8
Q

What are the benefits of starting ART early?

A
  • Maintain higher CD4 count + prevent irreversible damage to immune system
    Decrease risk for:
  • complications (even if CD4 >350): TB, non-Hodgkin’s lymphoma, Kaposi’s sarcoma, peripheral neuropathy, HIV-associated cognitive impairment
  • non-opportunistic conditions: CV, renal, liver disease, non-HIV associated malignancies, infections
  • HIV transmission
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9
Q

Limitations of earlier ART initiation

A
  • side effects + toxicities
  • drug resistance due to incomplete viral suppression: non-compliance
  • transmission of drug-resistant virus: need to check for resistant HIV even in ART-naive patients
  • less time to learn about HIV and TX, and to prepare for adherence
  • increase total time on medication -> treatment fatigue
  • cost
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10
Q

What are the recommended combinations for ART-naive patients?

A

2 NRTIs + 1 INSTI:
- tenofovir + emtricitabine + bictegravir
- tenofovir + emtricitabine + dolutegravir
- abacavir + lamivudine + dolutegravir (3 in 1 Triumeq)
1 NRTI + 1 INSTI:
- emtricitabine + dolutegravir
! not for: HIV RNA >500k copies/mL, HBV coinfection, before results of genotypic test or HBV test

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11
Q

Why is HBV coinfection contraindicated for emtricitabine + dolutegravir?

A
Requires at least 2 of the 3 following NRTIs:
- Lamivudine
- Emtricictabine
- Tenofovir
But only emtricitabine is used
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12
Q

Factors for selection of ART regimen

A
  • Patient’s understanding of HIV
  • Cost and availability
  • Adherence (less issue now): pill burden, dosing frequency, food and fluid considerations
  • Virologic efficacy: esp if patient has high viral load
  • Potential adverse effects: comorbidities (glucose intolerance, hyperlipidemia), DDI
  • Childbearing potential: teratogenic drugs
  • Genotypic drug resistance testing
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13
Q

What are the drug targets in ART?

A
  • Nucleoside reverse transcriptase
  • Integrase strand
  • Non-nucleoside reverse transcriptase
  • Protease
  • CCR5
  • Fusion
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14
Q

List the 5 NRTIs

A
Tenofovir
Emtricitabine
Abacavir
Lamivudine
Zidovudine
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15
Q

What are the disadvantages of NRTIs?

A
  1. Mitochondrial toxicity: most in zidovudine
    - lactic acidosis + hepatic steatosis
    - lipoatrophy
  2. Renal dose adjustment (except abacavir)
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16
Q

What are the ADRs of NRTIs?

A

All: NVD
- emtricitabine: hyperpigmentation
- tenofovir: renal impairment, decrease bone marrow density (alafenamide TAF < disoproxil fumarate TDF)
- abacavir: MI concern (avoid in high-risk CV);
hypersensitivity in HLA-B*5701 -> must test
* Hypersensitivity rxn: discontinue, don’t re-challenge
- zidovudine: myopathy, bone marrow suppression (anemia, neutropenia)
*monitor FBC for bone marrow suppression

17
Q

List the 4 INSTIs

A
  • Bictegravir
  • Dolutegravir
  • Raltegravir
  • Elvitegravir
18
Q

What are the advantages of bictegravir and dolutegravir?

A
  • high genetic barrier to resistance

- good virologic effectiveness

19
Q

What are some ADRs of INSTIs?

A
  • weight gain, ND, headache
  • CNS: depression, suicidality esp in preexisting psychiatric condition
  • raltegravir: pyrexia, increase creatine kinase (rhabdomyolysis)
20
Q

DDIs with INSTIs

A
  • decrease F with polyvalent cations

- CYP3A4 substrate: bictegravir, dolutegravir, elvitegravir

21
Q

What are the advantages and disadvantages of NNRTIs?

A

+ long t1/2 -> OD dosing
+ lower metabolic toxicity than PI
- low genetic barrier to resistance, cross resistance
- skin rash, SJS, QTc prolongation

22
Q

DDIs with NNRTIs

A

CYP450 DDI:

  • CYP3A4 substrate
  • efavirenz: induce CYP2D6, 2C19
    rilpivirine: concurrent PPI contraindicated
23
Q

Specific ADRs of NNRTIs

A

Efavirenz:
- hyperlipidemia - increase LDL-C + triglycerides
- neuropsychiatric - dizziness, depression, insomnia, abnormal dreams, hallucinations
- hepatotoxicity
Rilpivirine: depression, headache
- generally milder ADR than efavirenz

24
Q

List the 5 PIs

A
Ritonavir
Lopinavir
Atazanavir
Darunavir
Fosamprenavir
- formulated with PK enhancer: ritonavir or cobicistat
25
Q

What are the advantages and non-specific ADRs of PIs?

A

+ high genetic barrier to resistance, PI resistance uncommon
+ good GI tolerability, less lipid effects: darunavir + atazanavir
- metabolic - dyslipidemia, insulin resistance
- NVD, hepatotoxicity (chronic HBV/HCV), decrease BMD
- morphologic: fat maldistribution -> lipohypertrophy -> buffalo hump

26
Q

Specific ADRs/DDIs of ritonavir, darunavir and atazanavir

A

Ritonavir: paresthesia (numb extremeties), taste perversion
- potent CYP3A4 & 2D6 inhibitor
Darunavir: skin rash, SJS
Atazanavir: hyperbilirubinemia, QTc prolongation, skin rash
- Concurrent PPIs contraindicated

27
Q

ADRs for enfuvirtide

A
  • inj site reaction (SC BD): erythema, induration, nodule/cyst, pruritis, ecchymosis
  • increase risk of bacterial pneumonia
  • rare: hypersensitivity -> fever, chills, decrease BP
28
Q

What tests must be done for CCR5 antagonist?

A

Co-receptor tropism assay: must be CCR5 pre-dominant (not CXCR4 or dual/mixed tropism)

29
Q

ADRs of maraviroc (9)

A
  • abdominal pain
  • cough
  • dizziness
  • musuloskeletal
  • pyrexia
  • rash
  • URTI
  • hepatotoxicity
  • orthostatic hypotension