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HIV/AIDS Flashcards

1
Q

How to diagnose HIV?

A

Step 1: HIV antigen/antibody (ag/ab) (4th gen test)
-Will be positive if either antibodies or antigen detected
-If step 1 is +, go to step 2
Step 2: HIV 1 and 2 differentiation assay
-May show HIV1/HIV2 +/+, +/-, -/+, -/-
-Only the last one is indeterminate
-The first three confirm the dx
-If indeterminate, may be early disease, or step 1 was
false positive. If indeterminate, go to step 3.
Step 3: HIV-1 nucleic acid testing (can be HIV-1 Viral load)
-If positive, dx of HIV-1 is made

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2
Q

What’s the significance of the 4th gen HIV antigen/antibody test?

A

Can detect even the antigen (P24), not just the antibodies. Meaning we can get positive results earlier than before. Western Blot can fail to detect early on, until antibodies are present.

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3
Q

Who should be tested for HIV?

A

-All persons at least once in their life, not based on risk.
(any 13 to 64 yo in a healthcare setting)
-People known risk: Annually
-Consider opt-out vs HIV consent given is consent for care (separate signed consent not recommended)

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4
Q

What HIV-related labs should be obtained after HIV diagnosis?

A 
Plasma HIV RNA
CD4 cell count and %
HLA-B*5701
HIV resistance assay
Glucose-6-phosphate dehydrogenase
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5
Q

What Co-infection labs should be obtained after HIV diagnosis?

A

Hepatitis A, B, and C
Sexually transmitted infection (STI) screening
Tb Skin Test or interferon gamma release assay
Toxoplasma IgG

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6
Q

What basic labs should be ordered after HIV diagnosis?

A

CBC and differential
Metabolic panel
Fasting Lipid profile
Urinalysis

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7
Q

When should you start anti-retroviral therapy?

A

Right away!

  • We used to wait depending on CD4 count and viral load. Now we treat everyone every time.
  • START study showed significant benefits if you start right away (duh).
  • Reduces transmission rates too
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8
Q

People with HIV, who are on medications and are virally suppressed account for 51% of patients but are responsible for what percent of transmissions?

A

Zero Percent! Start the medications now!

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9
Q

What is U = U (regarding HIV)

A

Undetectable = untransmittable

  • Endorsed by CDC
  • People who take their meds as prescribed and achieve and maintain undetectable viral loads have effectively no risk of transmitting the virus to an HIV-negative partner.
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10
Q

What is first line therapy (as of 2020) for newly diagnosed HIV?

A

Integrase Inhibitor based regimens:
• Raltegravir + emtricitabine** + TDF or TAF
• Dolutegravir + emtricitabine** + TDF or TAF
• Dolutegravir + abacavir + lamivudine**
• Dolutegravir + lamivudinec*
• Bictegravir + emtricitabine + TAF

  • This two-drug regimen is only recommended if viral load (HIV RNA) < 500k/ml, no HBV co-infection, and after genotypic resistance testing.
  • *emtricitabine can be swapped with lamivudine
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11
Q

Recommended Regimens for Rapid Start for HIV?

A

Dolutegravir + Emtricitabine + TAF or TDF
Bictegravir + Emtricitabine + TAF
Darunavir/cobicistat + emtricitabine + TAF or TDF

*We want regimens that don’t require us to know the viral load, the resistance profile, CD4 count, presence of co-infections, and that have a high barrier to resistance.

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12
Q

Why have integrase inhibitors become so preffered?

A

They are better tolerated, and at least as good if not better at reducing viral loads as other classes.

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13
Q

What are the 4 integrase inhibitors?

A

Raltegravir (older)
Elvitegravir (older) (needs boosting)
Dolutegravir (newer) (neural tube defects)
Bictegravir (newer)

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14
Q

Raltegravir - Advantages and disadvantages

A

Advantages:
• Longest experience
• Fewest drug interactions
• Twice or once daily dosing

Disadvantages:
• Not a single-tablet regimen
• Pill burden
• Low barrier to resistance

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15
Q

Elvitegravir

A

Advantages:
• Single-tablet regimen
• Once daily dosing

Disadvantages:
• Requires boosting with cobicistat
• Many drug interactions
• Low barrier to resistance

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16
Q

Dolutegravir

A 
Advantages:
• Single-tablet regimen
• Non-tenofovir containing
• Once daily dosing
• High barrier to resistance
• Few drug interactions
Disadvantages:
• Risk of neural tube defects in pregnancy (if close to conception - pretty low though - still preferred).
• Co-formulated with abacavir
• Hypersensitivity and CVD risk
• Co-formulated with lamivudine
• Suboptimal for hepatitis B
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17
Q

Bictegravir

A 
Advantages:
• Single-tablet regimen
• Non-tenofovir containing
• Once-daily dosing
• High barrier to resistance
• Few drug interactions

Disadvantages:
• Only available in a single tablet

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18
Q

Integrase inhibitors and pregnancy

A

Use either raltegravir or dolutegravir, despite the DTG association with neural tube defects. If woman is in first 6 weeks or is trying to become pregnant, RAL may be preferred to DTG (the first 6 weeks is when neural tubes are closing).

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19
Q

Common Drug Drug interactions for integrase inhibitors during absorbtion?

A

Integrase inhibitors are negatively impacted by divalent and trivalent cations in antacids and multivitamins.

Raltegravir: do not coadminister. Use alternate agents
Elvitegravir: Separate doses by more than 2 hours
Dolutegravir: give DTG 2 hour before or 6 hours after
Bictegravir: give bictegravir 2 hr before antacid.

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20
Q

Common drug drug interactions for integrase inhibitors regarding metabolism?

A

Raltegravir has the least problems

Evitegravir is the worst! Induces 2c9. Comes with Cobicistat which is a very strong inhibitor of 3A4. CI with lovestatin and simvastatin. No more than 20 mg of atorvastatin. Cobixistat is also a MATE-1 inhibitor. What a dick!

Dolutegravir: Inhibits MATE-1 and OCT-2. CI with dofetilide

Bictegravir: Inhibits MATE-1 and OCT-2. CI with dofetilide.

*MATE-1 and OCT-2 inhibition reduces SCr secretion by the kidneys causing a small elevation in SCr early in therapy and then plateaus. No renal toxic. Metformin is excreted by the same pathway. Start at lower dose. Dofetalide is also excreted by this pathway!

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21
Q

Choosing between TAF and TAF for ART

A
  • Tenofovir disoproxil fumarate (TDF) is a prodrug that is converted to tenofovir (TFV) in the plasma and then enters the HIV target cell
  • TDF has been associated with diminished renal function and losses in bone mineral density
  • Tenofovir alafenamide (TAF) is a prodrug with 91% less circulating plasma TFV because it is converted to tenofovir within the target cell
  • Use of TAF significantly reduces the risk of kidney injury and bone mineral density losses in comparison with TDF
  • Both TDF and TAF are approved agents for the treatment of HIV and hepatitis B
    1. TAF is now used much more commonly

TAF is sAFe

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22
Q

Factors to consider when choosing abacavir

A

Risk for Hypersensitivity:
A. Incidence of hypersensitivity = 5-8%
B. Onset - within 6 weeks after initiating treatment
C. Multi-organ system syndrome with symptoms from ≥
2 of the following: Fever, rash, GI (nausea, vomiting,
diarrhea or abdominal pain), malaise/fatigue,
respiratory (cough or dyspnea)
D. Can be fatal upon re-challenge
E. HLA-B*5701 test has a 100% negative predictive value

Risk for CV disease:
A. Recent (within 6 months) or current use of abacavir has been found to be associated with an increased risk of cardiac events in several observational studies.
B. Current guidelines state that “In patients with high cardiac risk, consider avoiding abacavir-containing regimens”

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23
Q

What if someone has HIV and HBV?

A

Tenofovir containing regimens?

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24
Q

Lab testing after diagnosis?

A

At time of Dx:
HIV serology, CD4 count, HIV viral load, HIV resistance

At start of ART:
CD4, HLA-b*5701

At 4 weeks (2-8):
Viral load (expect 10 fold decrease, maybe undetectable).

At 3-6 months:
CD4 (expect 50 cell/cubic mm increase), Viral load

At treatment failure:
CD4, Viral Load, HIV resistance

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25
Q

What about live vaccines in HIV patients?

A

Not if their CD4 count is < 200

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26
Q

Who is at high risk for transmission of HIV and thus should potentially receive Pre-Exposure Prophylaxsis (PrEP)?

A

Anyone (gay or straight) who:

  • has sex with an HIV-positive partner
  • recently had an STI
  • has a high number of sexual partners
  • has doesn’t wear a condom consistently
  • does commercial sex work

Also:

  • straight people who are in high prevelance area/network
  • IV drug users with an HIV+ drug partner
  • IV drug user who shares equipment.
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27
Q

Which people at high risk of acquiring HIV are eligible for Pre-Exposure prophylaxis (PrEP)?

A
  • documented Negative HIV test
  • No signs/symptoms of acute HIV infection
  • Normal renal function and no CI medications
  • Document HBV negative and had vaccine
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28
Q

What agents are approved for PrEP?

A

Tenofovir-Emtribitabine in both forms: once daily
Truvada (TDF/FTC)
Descovy (FTC/TAF) -slightly better tolerated (fewer bone and kidney issues) and maybe more effective. Only approved for men!

29
Q

What is On-Demand PrEP?

A

Giving PrEP before or after sex. Study shows 86% reduction in transmission. However, most people in study took around 15-16 pills/month, which is more like PrEP than On-demand. Might have had better intracellular levels due to frequent use. Unclear if it would be as beneficial if used less frequently.

-CDC doesn’t endorse, but the WHO, the International Antiviral Society, and the British HIV association do.

30
Q

What is the recommended follow-up for pt’s receiving PrEP?

A

Every 3 months: HIV test, medication adherence counseling, behavioral risk-reduction support, side effect assessment, STI symptom assessment

At first 3 months, and every 6 thereafter: assess renal function

Every 3-6 months: test for STI’s

31
Q

How effective is PrEP when actually adhered to?

A

92% reduction!

32
Q

What timeframe should post-exposure prophy happen in?

A

72 hours for evaluation and treatment

33
Q

What is the recommended therapy for Post-Exposure prophy?

A

Withing 72 hours, start Tenofovir Disoproxil fumarate (TDF)/Emtricitibine (Truvada) plus raltegravir. 3 - drug therapy for 28 days.

Test for HIV at baseline and follow-up.
Also test for Hep-b and Hep-C and pregnancy.

34
Q

At what CD4 cell count do OI’s start to show?

A

CD4 < 200

~200 Oropharyngeal candidiasis and PCP
~100 Toxoplasmosis encephalitis and cryptococcal meningitis
~50 Mycobacterium Avium Complex (MAC) and cytomegalovirus retinitis

35
Q

How to treat and prevent PCP?

A

Treat for 21 DAYS
Treatment of Mild PCP:
TMP/SMX 15-20 mg/kg/day or 2 DS tabs TID

Severe PCP (pO2 < 70 mmHg)
TMP/SMX 15-20 mg/kg/day IV divided q6-8h
(may switch to po after clinical improvement)
Primary prophy (CD4 < 200) or secondary prophy:
TMP/SMX: 1 SS or 1 DS tab once daily.

*indications for adjunctive steroids are PaO2 < 70 mmHg on RA, or alveolar-arterial o2 gradient > 35 mmHg.

36
Q

When to give PCP prophy?

A

CD4 < 200, and continue until cd4 > 200 cells/mm3 for > 3 months with ART.

37
Q

How to treat Oropharyngeal Candidiasis as HIV OI?

A

Preferred: Fluconazole 100 mg PO daily 7-14 days

Alternatvies: Clotrimazole troches, miconazole mucoadhesive buccal tablets, nystatin oral susp.

*No prophy recommended.

38
Q

How to treat Toxoplasmosis Encephalitis HIV OI?

A

Preferred:
• Sulfadiazine + pyrimethamine + leucovorin

Alternatives:
• Clindamycin + pyrimethamine + leucovorin
• Atovaquone + pyrimethamine + leucovorin

*At least 6 weeks and then maintenance until asymptomatic and cd4 > 200 for 6 months on ART

39
Q

What about Toxoplasmosis Encephalitis prophy?

A

Preferred
• TMP-SMX 1 DS orally daily

Alternatives
• Dapsone daily + pyrimethamine + leucovorin weekly
• Atovaquone daily (can be prophy for PCP too)

*For pt with positive toxoplasma IgG and CD4 count < 100. Continue untill CD4 > 200 for > 3 months in response to ART.

40
Q

What about treatment for Cryptococcal Meningitis as HIV OI?

A

Induction (2 weeks):
Preferred
• Liposomal Amphotericin B + flucytosine
• Amphotericin B deoxycholate + flucytosine

Consolidation (8 weeks):
Preferred - Fluconazole 400 mg PO daily
Alt: Itraconazole 200 mg orally BID

Maintenance (at least 1 year and asympt and CD4 > 100 for 3 months in response to ART):
Fluconazole 200 mg PO daily.

*Prophy not generally rec’d.

41
Q

What about treatment of Disseminated Mycobacterium avium Complex (MAC) as an HIV OI

A

Preferred
• Clarithromycin orally + ethambutol orally or
• Azithromycin orally + ethambutol orally

Alternatives
• Adding a third or fourth drug to the preferred regimen above:
• Rifabutin, amikacin/streptomycin, or levofloxacin/moxifloxacin

42
Q

When and how to provide Primary prophy for MAC in HIV pts?

A

If not on ART and CD4 < 50.

Preferred
• Azithromycin 1200 mg orally once weekly
• Clarithromycin 500 mg orally twice
daily
• Azithromycin 600 mg orally twice weekly
Alternative
• Rifabutin 300 mg orally daily

*Considered when: CD4 count <50 cells/mm3, high mycobacterial loads (>2 log CFU/mL of blood), or the absence of effective ART. Not needed if ART started immediately.

43
Q

In pt’s with HIV OI’s, should you ever hold off on ART?

A

Yes. In patients with OI’s that affect the CNS, such as cryptococcal and tuberculous meningitis, mmediate ART may increase the risk of serious IRIS* (Immune Reconstitution Inflammatory Syndrome). A short delay may be warranted. Pt’s with non-OI’s should not delay start of ART.

44
Q

When to start ART following dx or tx of OI’s

A

Oropharyngeal candidiasis:Start ART as part of OI management
Pneumocystis pneumonia:Start ART within 2 weeks after PCP diagnosis
Toxoplasmosis encephalitis:Defer, but start ART within 2-3 weeks of toxoplasmosis treatment (avoiding IRIS)
Mycobacterium avium complex:Defer, but start ART within 2-3 weeks of MAC treatment (avoiding pill burden)
Mycobacterium tuberculosis
Start ART within 2 weeks if cell count <50 cell/mm3 and by 8 weeks for all others

45
Q

What is a big problem during transtions of care (into and out of hospital) for HIV patients?

A

Medication Error. Clinical pharmacists help.

46
Q

Notable side effect of Efavirenz?

A

Suicidality and Depression

47
Q

What’s a common ART switch?

A

Switching from TDF to TAF regimens.

48
Q

What are the renal cutoffs for TDF vs TAF?

A

CrCl > 50 for TDF

CrCl > 30 for TAF (TAF IS SAFE!)

49
Q

Who should receive non-occupational post-exposure HIV prophylaxis? (nPEP)

A

If partner is HIV+ or if status is unknown but person is high risk (MSM, IV drugs, sex worker) or if sexually assaulted and the person engaged in:

  • condomless receptive anal or vaginal sex
  • percutanteous exposure to blood (or bodily fluids contaminated with blood)

nPEP is not needed if partner is HIV-, or if HIV+ but on ART and undetectable viral load. Start nPEP until viral load can be determined though.

50
Q

What regimen should be used for HIV nPEP?

A

A three drug regimen. Most commonly Tenofovir disoproxil fumarate/emtricitabine (Truvada) plus an integrase inhibitor (raltegravir or dolutegravir). It’s not cear if TAF would be as good as TDF, since extracellular concentrations are lower. However, with PrEP it’s non-inferior. Dolutegravir is usually preferred, but if possible pregnant, raltegravir is preferred.

51
Q

Who needs to be screened for HLA-B*5701 and why? (HIV)

A

Pts who will be taking abacavir. Has a 100% negatvie predictive value for abacavir hypersensitivity reaction.

52
Q

Does Tenofovir and Emtricitabine have activity against HBV?

A

Yes. Yes they do. Abrupt discontinuation may lead to a flare up.

53
Q

How soon should you intiate PEP (post-exposure prophylaxis of a healthcare worker)?

A

Goal is within 1-2 hours. Don’t bother after 72 hours, unless very high risk exposures (needle stick from needle that was in a vein or artery of HIV+ person), can go out to a week.

54
Q

Who should get PEP?

A

Health care workers with a percutaneous mucous membrane or non-intact skin exposure to blood or bloody body fluids of a patient with known HIV. If HIV status is unknown, give PEP until testing results available, particularly if the person is high risk for HIV.

55
Q

What is the preferred regimen for PEP?

A

Same as for nPEP. Tenofovir disoproxil fumarate-emtricitabine (Truvada) (TDF/FTC) + either dolutegravir daily or raltegravir BID. Treat for 28 days.

Dolutegravir regimen preferred unless pregnancy concernes.

56
Q

A patient with CD4 count of 100-200 should receive what prophy?

A

PCP primary and secondary prophy: Bactrim 1 DS or SS tab daily until CD4 count > 200 for 3 months. (Dapsone for sulfa allergic).

*Person is at risk of candidiasis, but no prophy is rec’d.

57
Q

A person with actual PCP pneumonia should receive what treatment?

A

TMP/SMX 15-20 mg/kg/day divided or 2 DS tabs TID.

*If severe give IV.

58
Q

What prophy should an HIV patient with CD4 count of 50-100 recieve?

A

Concern for Toxoplasmosis + PCP (CD4 < 200).

If Toxoplasmosis IgG positive, give bactrim 1 ds daily until cd4 is > 200 on ART.

Alternative (e.g. sulfa allergic): Dapsone + pyramethamine + leucovorin WEEKLY. OR Atovaquone Daily (also works for PCP prophy).

Pt is at risk for cryptococcal meningitis, but primary prophy not rec’d.

59
Q

How do you treat toxoplasmosis?

A

Sulfadiazine + Pyrimethamine + leucovorin for at least 6 weeks and intul asymptomatic and CD4 > 200 for > 6 months!

*Can replace Sulfadiazine with clinda or atovaquone as alternative.

60
Q

What if a person’s CD4 count is < 50 cells/mm3, what prophy do you need?

A

Need to proph for PCP (CD4 < 200), toxoplasmosis (CD4 < 100, if IgG+), and now MAC! NOT NEEDED IF IMMEDIATELY STARTING ART. Continue until ART is started.

For MAC: give a “MACrolide!”

  • Azithromycin 1,200 mg weekly
  • Clarithromycin 500 mg BID
  • Azithromyin 600 mg twice a week.
  • Alternative agent is Rifabutin 300 mg daily.
61
Q

What about treatment for MAC (in HIV patients)

A

First line: Macrolide + Ethambutol

Alternative: add 3rd or 4th drug to above: rifabutin, amikacin/streptomycin, levaquine/moxyfloxacin.

62
Q

When should you start ART if you have PCP?

A

WITHIN 2 weeks of PCP diagnosis! (E.G. don’t really wait)

63
Q

When should you start ART if you have Oropharyngeal Candidiasis?

A

Start right away

64
Q

When should you start ART if you have Toxoplasmosis encephalitis?

A

Wait, but start within 2-3 weeks of treatment (concern for IRIS (Immune Reconstitution Inflammatory Syndrom).

65
Q

When should you start ART if you have MAC?

A

Wait, but start within 2-3 weeks of treatment (concern for pill burden).

66
Q

When should you start ART if you have TB?

A

Within 2 weeks if CD4<50, and by 8 weeks for all others. (E.g. no need to wait, and early start improves survival for pts with low CD4 count.)

67
Q

Dofetilide is CI with which integrase inhibitors?

A

Dolutegravir and Bictegravir (OCT2 and MATE-1 interaction)

68
Q

Which integrase inhibitor is CI with statins (except lipitor can be given but max dose is 20 mg.

A

elvitegravir (and cobixistat)

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