HIV Flashcards

1
Q

Life Cycle

A
  1. Viral Entry
  2. Reverse transcriptase creates viral DNA
  3. Viral integrase integrates viral DNA into nucleus and genome
  4. Transcription/translation occurs forming viral
    proteins
  5. Proteins are then cleaved and used in new HIV organism assembly
  6. HIV organisms mature an bud off host cell to infect other cells
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2
Q

HIV Etiology

A
  • Retrovirus (RNA => DNA via reverse transcriptase)
  • Infects the immune system, mainly CD4 receptors of T-cells
  • Can also infect monocytes, macrophages, and dock CD4- cells to infect them
  • HIV-1 is majority of US cases
  • HIV-2 is less virulent and mainly seen in Africa
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3
Q

HIV Diagnostic Tests

A
  • HIV Antibodies: most common test for established infection
  • HIV-1 RNA: used for actute HIV and indeterminate WB
  • HIV p24 Antigen: 4th generation EIA
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4
Q

Routine Screening for HIV Infection

A
  1. All patients aged 13-64 in all health care settings
  2. Patients seeking treatment for STDs
  3. Patients initiating tuberculosis treatment
  4. Pregnant patient
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5
Q

HIV Stages

A
  • Stage 0: Early HIV infection
  • Stage 1: CD4>500, >=26%, no AIDS-defining condition
  • Stage 2: CD4 200-499, 14-26%, no AIDS-defining condition
  • Stage 3: CD4 <200, <14%, no documentation of AIDS-defining condition
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6
Q

HIV Transmission

A
  • Found in blood, urine, semen, vaginal secretions, uterine cervix, breast milk, CSF, alveolar fluid
  • Unprotected sex with infected partner
  • Sharing needles
  • Infection from blood products
  • Transmission from mother to fetus
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7
Q

HIV Goals of Treatment

A
  • Reduce HIV-related morbidity (prolong duration and quality of survival)
  • Restore and/or preserve immunologic function
  • Maximally and durably suppress HIV viral load
  • Prevent HIV transmission
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8
Q

Adherence

A
  • Major determinant of degree and duration of viral suppression
  • Poor adherence associated with virologic failure
  • Optimal suppression requires excellent adherence
  • Suboptimal adherence is common
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9
Q

Predictors of Inadequate Adherence

A
  • Regimen complexity and pill burden
  • Poor clinician-patient relationship
  • Active drug use or alcoholism
  • Unstable housing
  • Mental illness (especially untreated depression)
  • Lack of patient education
  • Medication AE (fear of them)
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10
Q

When to Start ART

A
  • Art is recommended for treatment and for prevention
  • A1 recommendation
  • Recommended regardless of CD4 count
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11
Q

ART Initiation Considerations

A
  • ART should be started as soon as possible, could be deferred due to clinical/psychological factors
  • Indefinite treatment is required, doesn’t cure HIV
  • Address strategies to optimize adherence
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12
Q

Considerations for HAART

A
  • ARV Resistance: prior regimens and resistance tests
  • Comorbid conditions: renal disease, HBV, osteoporosis, pregnancy
  • Drug absorption: acidic stomach, chelators, food requirement
  • Drug interactions: need current medication list
  • Insurance/formulary
  • Patient preference: pill count, food requirements, dosing frequency
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13
Q

Baseline Data

A
  • Complete metabolic panel
  • CBC with differential
  • Urinalysis
  • Blood glucose
  • Lipid panel
  • Pregnancy test
  • Current medication list
  • Comorbidities
  • CD4 Count (All)
  • HIV Viral Load (All)
  • Serologies for Hep A/B/C (All)
  • Genotype-test for resistance (All)
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14
Q

CD4 Count Importance

A
  • Used to stage disease
  • Immune function assessment
  • Assess if OI prophylaxis is needed
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15
Q

HIV Viral Load Importance

A
  • May help provider decide on regimen

- Baseline value which is tracked to gauge treatment efficacy and adherence

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16
Q

Drug Resistance Testing

A

Before ART Initiation:

  • Transmitted resistance occurs in 10-17% of infected patients
  • Absence of therapy may decline over time for detection but still cause treatment failure
  • Identification of resistance mutations can optimize treatment outcomes
  • Resistance testing is recommended for all at entry to care (include INSTI if suspected)
  • Recommended for all pregnant women

Virological Failure:

  • Perform while patient is taking ART, or =<4 weeks after D/C therapy
  • Interpret in combination with history of ARV exposure and adherence
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17
Q

HLA-B*5701 Screening

A
  • Recommended before starting ABC, to reduce risk of hypersensitivity reaction
  • Positive patients shouldn’t receive ABC
  • Positive status should be recorded as ABC allergy
  • If testing isn’t available, ABC may be initiated but only after counseling and with appropriate monitoring for HSR
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18
Q

Coreceptor Tropism Assay

A
  • Should be performed when a CCR5 antagonist is being considered
  • Phenotype assays have been used; genotype test now available but has been studied less thoroughly
  • Consider in patients with virological failure on CCR5 antagonist
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19
Q

Initial ART Regimens: DHHS Categories

A
  • Recommended in Most people: easy to use, durable efficacy, favorable tox/tolerability profiles
  • Recommended in Certain Clinical Situations: Effective but have potential disadvantages, limitations in populations, less supporting data, may be optimal for certain patients
  • Other: reduced virological activity, greater toxicities, higher pill burden, other limiting factors
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20
Q

Initial Regimen (HAART)

A

NRTI Background + Integrase Inhibitor

21
Q

Preferred NRTI Backbone Choices

A
  • Tenofovir + Emtricitabine (Truvada)
  • Tenofovir alafenamide (TAF) + emtricitabrine (Descovy)
  • Abacavir + Lamivudine only as part of Triumeq (dolutegravir too): only if HLA-b*5701 is absent
22
Q

Initial Regimen Options

A
  • Highly vary
  • Can be INSTI, NNRTI, PI, or INSTI based
  • Can focus on single pill regimens
  • Differ by guidelines
  • NRTI-sparing (when it can’t be used)
23
Q

Special Consideration + Initial Regimens

A
  • TDF not recommended in those with kidney or bone disease
  • 2-drug regimens are only recommended when abacavir, TAF, or TDF can’t be taken
  • Pregnant individuals should initiate ART ASAP
24
Q

Lab Monitoring: Viral Load

A
  • 2-4 weeks after starting ART and no later than 8, repeat at 4- and 8- weeks until undetectable
  • Goal to be undetectable within 8-24 weeks
  • Every 6 mo if undetectable after 2 years
  • If regimen is modified, repeat viral load within 4-8 weeks after change
25
Q

Lab Monitoring: CD4

A
  • Adequate response to therapy: 50-150 cell increase during 1st year of ART
  • 3 mo after initiation of ART is preferred for treatment
  • If stable CD4 (300-500) after 2 years, measure every year
  • If CD4 > 500 after 2 years, monitoring is optional
26
Q

Bictegravir Advantages

A
  • Once daily and coformulated with TAF/FTC
  • Non-inferior to DTG
  • Low-risk resistance
  • With or without food
  • Few drug interactions
27
Q

Bictegravir Disadvantages

A
  • Cannot be used with rifampin
  • Limited data (new)
  • Raised SCr
  • Limited pregnancy data
  • Concern for neural tubal defects
28
Q

Dolutegravir Advantages

A
  • Superior to DRV and EFV
  • Once-daily
  • Available as single agent
  • High resistance barrier
  • Few drug interactions
  • With or without food
  • Superior to RTG in experienced patients
29
Q

Dolutegravir Disadvantages

A
  • Raises SCr
  • Higher rates of insomnia/headache
  • With ABC/3TC = largest tablet
  • Concern for neural tubal defects
30
Q

Elvitegravir Advantages

A
  • Once daily

- Co-formulated

31
Q

Elvitegravir Disadvantages

A
  • Requires PK booster
  • Low resistance barrier
  • Drug interactions
  • Raises SCr
  • Food
  • Avoid in pregnancy
  • Concern for neural tubal defects
32
Q

Raltegravir Advantages

A
  • Superior to ritonavir-boosted DRV, ATV
  • Longest safety record
  • Fewest DDI
  • With or without food
33
Q

Raltegravir Disadvantages

A
  • Not co-formulated
  • Lower barrier to resistance than DTG, BTG
  • Higher pill burden (own pill, not co-formulated)
  • Concern for neural tubal defects
34
Q

Patient Characteristics Considerations + Initiating ART

A
  • HIV RNA; CD4 count
  • HIV resistance test results
  • HLA-B*5701 status
  • Patient preferences
  • Anticipated adherence
35
Q

Comorbidities Considerations + Initiating ART

A
  • CV disease, hyperlipidemia, renal disease, osteoporosis, psychiatric illness
  • Pregnancy or pregnancy potential
  • Coinfections: HCV, HBV, TB
36
Q

Regimen Characteristics Considerations + Initiating ART

A
  • Genetic barrier to resistance
  • Potential adverse effects
  • Drug interactions with other medications
  • Convenience (pill #/frequency)
  • Cost
37
Q

CD4 < 200: Drugs to Avoid

A
  • Rilpivirine

- Darunavir/r + Raltegravir

38
Q

HIV RNA > 100,000: Drugs to Avoid

A
  • Rilpivirine based ART

- ABC/3TC + EFV or ATV/r

39
Q

HLAB*5701 Positive: Drugs to Avoid

A

ABC

40
Q

HIV Drugs + Food

A
  • Have to boost? Take with food
  • Rilpivirine also requires food
  • EFV requires an empty stomach (bedtime)
  • Raltegravir and Dolutegravir can be taken without regards to food
41
Q

eGFR < 60 + HIV Drugs

A
  • Avoid TDF
  • Use ABC or TAF (latter used in eGFR >= 30)

-LPV + 3TC or DRV/r + RAL can be used is TAF or ABC can’t be used (unlikely scenario)

42
Q

Osteopororsis + HIV Drugs

A
  • Avoid TDF

- Use ABC or TAF

43
Q

Psychiatric Illness + HIV Drugs

A
  • Consider avoiding EFV and Rilpivirine

- Exacerbates symptoms and can be associated with suicidality

44
Q

HIV-associated Dementia + HIV Drugs

A
  • Avoid EFV

- Favor Darunavir or DTG-based regimens

45
Q

Methadone + HIV Drugs

A
  • Avoid EFV-based regimens if receiving methadone

- May have to increase methadone dose if EFV must be used

46
Q

Cardiac Risk: Drugs to Avoid

A
  • ABC
  • Lopinavir/r
  • EFV or Rilpivirine regimens especially with other torsades risk drugs
47
Q

Hyperlipidemia + HIV Drugs

A

Avoid

  • PI based regimens (regardless of booster)
  • EFV
  • Elvitegravir/c

-TDF beneficial for cholesterol

48
Q

HBV + HIV Drugs

A

Use TDF or TAF with Emtricitabine (FTC) or Lamivudine (3TC) whenever possible

49
Q

TB + HIV Drugs

A
  • TAF not recommended to use with rifamycins (decreases its exposure)
  • In a PI-based regimen, use rifabutin instead of rifampin

If Rifamycins used:

  • EFV (no adjustment)
  • Raltegravir (800 mg BID)
  • DTG (50 mg BID if no significant INSTI mutations)