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1-NAPLEX (Review Daily) > HIV > Flashcards

HIV Flashcards

1
Q

Who are considered high-risk for HIV infection?

A

1- Sharing needles
2- High-risk sexual behaviors (men who have sex with men, sex with multiple partners, etc.)
3- History of TB or Hepatitis infection

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2
Q

Signs of an Acute (early) Infection?

A

Non-specific flu-like symptoms
-Lasts few days to several weeks
-Patients become asymptomatic after this initial phase

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3
Q

When is the testing window for HIV detection?

A

4-12 weeks

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4
Q

Diagnostic Testing of HIV

A

Step 1: HIV antigen/antibody immunoassay

Step 2: If positive, a confirmatory test is needed to differentiate HIV-1 from HIV-2.
-HIV-1 is predominately in USA

Step 3: If confirmatory test is ‘Indeterminate’ or ‘Negative’, HIV Nucleic Acid Test is done to quantify the viral load.

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5
Q

Stage 1 & Stage 2 of HIV infection

A

Stage 1: Binding/Attachment
HIV attaches to a CD4 receptor and the CCR5 and/or CXCR4 co-receptors on the surface.
DRUGS:
-Maraviroc (CCR5 ONLY antagonist)
-Fostemsavir (Attachment inhibitor)
-Ibalizumab (Post-attachment inhibitor)

Stage 2: Fusion
The HIV viral envelope fuses with the CD4 cell membrane. HIV enters the host cell and releases HIV RNA, viral proteins and enzymes needed for replication.
DRUGS:
-Enfuvirtide (Fusion inhibitor)

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6
Q

Stage 3 & Stage 4 of HIV infection

A

Stage 3: Reverse Transcription
HIV RNA is converted to HIV DNA by reverse transcriptase. HIV DNA can then enter the CD4 cell nucleus.
DRUGS:
-NRTI: Emtricitabine, Tenofovir, Abacavir, Lamivudine, Zidovudine
-NNRTI: Efavirenz, Rilpivirine

Stage 4: Integration
Once inside of the CD4 nucleus, Integrase is released and used to insert HIV DNA into the host-cell DNA.
DRUGS:
INSTI: Bictegravir, Dolutegravir, Raltegravir, Elvitegravir
“-tegravir”

*NRTI: Nucleoside Reverse Transcriptase Inhibitor
NNRTI: Non-nucleoside reverse transcriptase inhibitor
INSTI: Integrase strand transfer inhibitors

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7
Q

Stage 5, Stage 6, Stage 7 of HIV Infection

A

Stage 5: Replication
Host cell is used to transcribe and translate HIV DNA into HIV RNA and proteins
DRUGS: None

Stage 6: Assembly
New HIV RNA, proteins and enzymes move to the cell surface and assemble into immature HIV.
DRUGS: None

Stage 7: Budding and Maturation
Immature HIV pushes out of the CD4 cell and protease creates mature HIV that can infect other cells.
DRUGS:
-PI: Atazanavir, Darunavir, etc
ending with ‘navir’

*PI: Protease Inhibitors

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8
Q

What important test should be done BEFORE starting Abacavir?

A

HLA-B*5701 allele

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9
Q

What important test should be done BEFORE starting Maraviroc?

A

Tropism Assay

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10
Q

Goals of ART

A

1- Achieve and Maintain suppression through undetectable viral load.
-Consider non-adherence or resistance if this is not achieved.

2- Restore and Preserve Immune Function through increased CD4 count

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11
Q

HIV ART Regimen

A

Backbone: 1 base + 2 NRTI
Base - Boosted PI, NNRTI or INSTI

NRTI backbone:
-TDF or TAF or Abacavir PLUS
-Emtricitabine or Lamivudine

*PI can be boosted with Ritonavir or Cobicistat

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12
Q

Preferred Initial ART Regimens for treatment-naive adults

A

One tablet daily:
1- Biktarvy (Bictegravir/Emtricitabine/TAF)
2- Triumeq (Dolutegravir/Abacavir/Lamivudine)
3- Dovato (Dolutegravir/Lamivudine)

Two tablets daily
1- Trivicay + Truvada (Dolutegravir + Emtricitabine/TDF)
2- Trivicay + Descovy (Dolutegravir + Emtricitabine/TAF)

*lamivudine and emtricitabine are interchangeable but should not be used together.

*All the above contains an integrase inhibitor with a high barrier to resistance (Bictegravir and Dolutegravir)

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13
Q

When should we avoid Dovato?

A

-HIV RNA > 500,000 copies/mL
-Known/Unknown Hepatitis B coinfection
-HIV genotyping testing is not yet available

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14
Q

What are the NRTIs?

A
  • Abacavir (Ziagen)
  • Emtricitabine (Emtriva)
  • Lamivudine (Epivir)
  • Tenofovir DF (Viread) <– greater systemic exposure compared to TAF
  • Tenofovir AF
  • Zidovudine (Retrovir)

MOA: Competitively inhibit the reverse transcriptase enzyme.
-Resistance develops easily in this class, that is why we need 2 in our regimen

-Zidovudine is administered IV during labor and delivery in patients with an unknown HIV RNA level or RNA > 1000 copies/mL

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15
Q

NRTI Issues and Features

A
  • All NRTI: warning for lactic acidosis and hepatomegaly
    -Common side effects: nausea, diarrhea
    -Abacavir: test for HLA-B*5701 - contraindicated if positive
    -Tenofovir (TDF>TAF): renal impairment and decreased bone mineral density
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16
Q

Boxed Warnings for ART drugs

A

1) Emtricitabine, Tenofovir, Lamivudine: Severe acute HBV liver damage if abrupt discontinuation with HBV co-infection

2) Maraviroc: Hepatotoxicity

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17
Q

What are the INSTIs?

A

1- Bictegravir (In Biktarvy)
2- Dolutegravir (Trivicay)
3- Elvitegravir (In Genvoya and Stribild)
4- Raltegravir (Isentress)
5- Cabotegravir
‘-tegravir’

MOA: Block the integrase enzyme, preventing HIV DNA from inserting into the host cell DNA.

Side Effects: Weight gain and nervous/psychiatric effects

*Elvitegravir is co-formulated with cobicistat, a strong CYP3A4 inhibitor
*All INSTIs interact with cations. Take INSTI 2 hours before or 6 hours after

18
Q

What are the NNRTIs?

A

1- Efavirenz
2- Rilpivirine
3- others (Doravirine, Etravirine, Nevirapine)

MOA: non-competitively inhibit the reverse transcriptase enzyme.

Side Effects: Hepatotoxicity, Rash (SJS/TEN)

*Rilpivirine requires an acidic environment for absorption. It has a drug interaction with acid suppressants.

*Efavirenz should be taken on an empty stomach, preferrable at bedtime. Associated with psychiatric symptoms

19
Q

What are the most common PI?

A

1- Atazanavir (Reyataz) - take with food, needs acidic environment
2- Darunavir (Prezista) - take with food

Less common PI include:
-Fosamprenavir
-Lopinavir/Ritonavir
-Tipranavir

*All PIs are recommended to be administered with a PK booster (Ritonavir or Cobicistat).
*No renal adjustments needed

20
Q

Key Features with Protease Inhibitors

A

Atazanavir:
- Hyperbilirubinemia (reversible)
- Unboosted: avoid PPIs
- Boosted: take 12 hours after PPI

Darunavir:
- Sulfa allergy

21
Q

HIV PK Boosters

A

1- Cobicistat (150 once daily)
2- Ritonavir (100-200 once/twice daily)

-Take with food

22
Q

Drugs which are contraindicated or should generally be avoided with PI & PK boosted drugs?

A

1) Alpha-1: Alfuzosin, Silodosin, Tamsulosin
2) Amiodarone, Dronedarone
3) Apixaban, Rivaroxaban, Ticagrelor
4) Azole Antifungals
5) Lovastatin, Simvastatin
6) Sildenafil, Tadalafil
7) Strong CYP3A4 inducers (St. johns Wort, Rifampin, Carbamazepine)

23
Q

Entry, Attachment and Capsid Inhibitors

A

-Less commonly used
-Usually reserved for treatment-experienced patients who has developed resistance
-Both are substrates for CYP3A4

1) Maraviroc (CCR5 Antagonist)
2) Fostemsavir (Attachment Inhibitor)
3) Ibalizumab (Post-Attachment Inhibitor) (Trogarzo) - IV
4) Enfuvirtide (Fusion Inhibitor) -subQ injection
5) Lenacapavir (Capsid Inhibitor)

*Lenacapavir has a PO loading dose then subQ injection every 6 months

24
Q

What are the 3-component INSTI Combination Products?

A

1) Biktarvy (Bictegravir/Emtri/TAF) - 1st line
2) Triumeq (Dolutegravir/Abacavir/Lamivudine) -1st line
3) Stribild (Elvitegravir/Cobi/Emtri/TDF)
4) Genvoya (Elvitegravir/Cobi/Emtri/TAF)

Triumeq requires HLA-B5701 testing
*Stribild and Genvoya needs to be taken with food because of Cobicistat.

25
Q

What are the 2-component INSTI Combination Products?

A

1) Dovato (Dolutegravir/Lamivudine) - 1st line
2) Juluca (Dolutegravir/Rilpivirine)
3) Cabenuva (Cabotegravir/Rilpivirine) -IM

*Juluca and Cabenuva are indicated to replace a previous regimen in patients with an undetected viral load.

26
Q

What are the NNRTI Combination Products?

A

1) Delstrigo (Doravirine/Lamivudine/TDF)
2) Atripla (Efavirenz/Emtri/TDF)
3) Symfi (Efavirenz/lamivudine/TDF)
4) Complera (Rilpivirine/ Emtri/TDF)
5) Odefsey (Rilpivirine/Emtri/TAF)

*Atripla is a discontinued brand, but the generic version is available.

*Atripla and Symfi should be taken on an empty stomach due to Efavirenz.

*Complera and Odefsy should be taken with food due to Rilpivirine.

27
Q

What is the PI-based Combination Product?

A

Symtuza (Darunavir/Cobi/Emtri/TAF)

28
Q

What Combination Products must be used with additional ART to make a complete regimen?

A

1) Epzicom (Abacavir/Lamivudine)
2) Trizivir (Abacavir/Lamivudine/Zidovudine)
3) Descovy (Emtri/TAF)
4) Truvada (Emtri/TDF)
5) Combivir (Lamivudine/Zidovudine)
6) Cimduo (Lamivudine/TDF)
7) Evotaz (Atazanavir/Cobicistat)
8) Prezcobix (Darunavir/Cobicistat)

29
Q

CrCl cut-offs for HIV drugs

A

CrCl < 70: Stribild
CrCl < 50: TDF-containing products
CrCl < 30: TAF-containing products

30
Q

Who are indicated for PrEP?

A

1- Multiple sex partners
2- Men who have sex with Men
3- IV drug use

31
Q

What should be done before starting PrEP?

A

1- Confirm the patient is HIV-negative
2- Screen for recent symptoms of HIV
3- Labs (sCr, HepB)

32
Q

PrEP treatment

A

1- Truvada (1 tab daily)
2- Descovy (1 tab daily) - not for females
3- Apretude (Cabotegravir) IM monthly for 2 doses, then once every 2 months

  • Patient has to test for HIV every 3 months. If negative, continue PrEP.
    -Continue for as long as patient is at risk for HIV
33
Q

Post-Exposure Prophylaxis (PEP)

A

-Before starting, test for HIV, sCr and HepB.
-Start within 72 hours of exposure
-Complete 3-drug regimen x 28 days

Treatment:
Truvada + Dolutegravir or Raltegravir

34
Q

Who are considered Immunocompromised?

A

1- HIV patients
2- Use of systemic steroids for ≥ 14 days at a prednisone dose of ≥ 20 mg/day or ≥ 2 mg/kg/day.
3- Asplenia
4- Use of immunosuppressants
5- Use of Cancer Chemotherapy

35
Q

What are the common opportunistic infections requiring primary prophylaxis?

A

1- Pneumocystis jirovecii pneumonia (PJP or PCP)
2- Toxoplasmosis gondii encephalitis
3- Mycobacterium avium complex (MAC)

*Candida infections are usually common but prophylaxis is not usually recommended.

36
Q

Pneumocystis jirovecii Pneumonia (PCP or PJP)

A

PROPHYLAXIS
Start: CD4 cell < 200
Preferred Tx: Bactrim DS daily
Alternative Tx:
-Bactrim DS 3xweek
-Dapsone
-Dapsone+Pyrimethamine+Leucovorin
-Atovaquone
-Atovaquone+Pyrimethamine+Leucovorin

D/c when CD4 > 200 for > 3 months on ART
*Leucovorin is added as a rescue therapy to reduce the risk of developing pyrimethamine-induced myelosuppression.

TREATMENT
-Bactrim DS ± Prednisone/Methylprednisolone x 21 days

37
Q

Toxoplasma gondii Encephalitis

A

PROPHYLAXIS
Start: CD4 cell < 100 & Toxoplasma IgG Positive
Preferred Tx: Bactrim DS daily
Alternative Tx:
-Bactrim DS 3xweek
-Dapsone+Pyrimethamine+Leucovorin
-Atovaquone
-Atovaquone+Pyrimethamine+Leucovorin

D/c when CD4 > 200 for > 3 months on ART

TREATMENT
-Primethamine+Leucovorin+Sulfadiazine

38
Q

Mycobacterium avium complex (MAC)

A

-Not recommended if ART is started immediately.

PROPHYLAXIS
Start: CD4 cell < 50 & Not on ART
Preferred Tx: Azithromycin 1200 mg weekly
Alternative Tx:
-Azithromycin 600 mg twice weekly
-Clarithromycin 500 mg BID

D/c when taking fully suppressive ART

TREATMENT
Preferred: Clarithromycin or Azithromycin + Ethambutol

39
Q

Other Opportunistic Infections

A

Candidiasis
Tx: Fluconazole

Cryptococcal Meningitis
Tx: Amphotericin B + Flucytosine

Cytomegalovirus
Tx: Valganciclovir or Ganciclovir

40
Q

What to use if the patient has a Sulfa Allergy for PCP?

A

Atovaquone
Dapsone
Pentamidine

41
Q

What to use if the patient has a G6PD deficiency?

A

Atovaquone
Pentamidine

1-NAPLEX (Review Daily) (20 decks)

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