HIV Flashcards
1
Q
Life Cycle
A
- Viral Entry
- Reverse transcriptase creates viral DNA
- Viral integrase integrates viral DNA into nucleus and genome
- Transcription/translation occurs forming viral
proteins - Proteins are then cleaved and used in new HIV organism assembly
- HIV organisms mature an bud off host cell to infect other cells
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
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
4
Q
Routine Screening for HIV Infection
A
- All patients aged 13-64 in all health care settings
- Patients seeking treatment for STDs
- Patients initiating tuberculosis treatment
- Pregnant patient
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
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
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
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
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)
10
Q
When to Start ART
A
- Art is recommended for treatment and for prevention
- A1 recommendation
- Recommended regardless of CD4 count
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
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
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)
14
Q
CD4 Count Importance
A
- Used to stage disease
- Immune function assessment
- Assess if OI prophylaxis is needed
15
Q
HIV Viral Load Importance
A
- May help provider decide on regimen
- Baseline value which is tracked to gauge treatment efficacy and adherence
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
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
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
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
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
Lab Monitoring: CD4
- 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
Bictegravir Advantages
- Once daily and coformulated with TAF/FTC
- Non-inferior to DTG
- Low-risk resistance
- With or without food
- Few drug interactions
27
Bictegravir Disadvantages
- Cannot be used with rifampin
- Limited data (new)
- Raised SCr
- Limited pregnancy data
- Concern for neural tubal defects
28
Dolutegravir Advantages
- 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
Dolutegravir Disadvantages
- Raises SCr
- Higher rates of insomnia/headache
- With ABC/3TC = largest tablet
- Concern for neural tubal defects
30
Elvitegravir Advantages
- Once daily
| - Co-formulated
31
Elvitegravir Disadvantages
- Requires PK booster
- Low resistance barrier
- Drug interactions
- Raises SCr
- Food
- Avoid in pregnancy
- Concern for neural tubal defects
32
Raltegravir Advantages
- Superior to ritonavir-boosted DRV, ATV
- Longest safety record
- Fewest DDI
- With or without food
33
Raltegravir Disadvantages
- Not co-formulated
- Lower barrier to resistance than DTG, BTG
- Higher pill burden (own pill, not co-formulated)
- Concern for neural tubal defects
34
Patient Characteristics Considerations + Initiating ART
- HIV RNA; CD4 count
- HIV resistance test results
- HLA-B*5701 status
- Patient preferences
- Anticipated adherence
35
Comorbidities Considerations + Initiating ART
- CV disease, hyperlipidemia, renal disease, osteoporosis, psychiatric illness
- Pregnancy or pregnancy potential
- Coinfections: HCV, HBV, TB
36
Regimen Characteristics Considerations + Initiating ART
- Genetic barrier to resistance
- Potential adverse effects
- Drug interactions with other medications
- Convenience (pill #/frequency)
- Cost
37
CD4 < 200: Drugs to Avoid
- Rilpivirine
| - Darunavir/r + Raltegravir
38
HIV RNA > 100,000: Drugs to Avoid
- Rilpivirine based ART
| - ABC/3TC + EFV or ATV/r
39
HLAB*5701 Positive: Drugs to Avoid
ABC
40
HIV Drugs + Food
- 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
eGFR < 60 + HIV Drugs
- 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
Osteopororsis + HIV Drugs
- Avoid TDF
| - Use ABC or TAF
43
Psychiatric Illness + HIV Drugs
- Consider avoiding EFV and Rilpivirine
| - Exacerbates symptoms and can be associated with suicidality
44
HIV-associated Dementia + HIV Drugs
- Avoid EFV
| - Favor Darunavir or DTG-based regimens
45
Methadone + HIV Drugs
- Avoid EFV-based regimens if receiving methadone
| - May have to increase methadone dose if EFV must be used
46
Cardiac Risk: Drugs to Avoid
- ABC
- Lopinavir/r
- EFV or Rilpivirine regimens especially with other torsades risk drugs
47
Hyperlipidemia + HIV Drugs
Avoid
- PI based regimens (regardless of booster)
- EFV
- Elvitegravir/c
-TDF beneficial for cholesterol
48
HBV + HIV Drugs
Use TDF or TAF with Emtricitabine (FTC) or Lamivudine (3TC) whenever possible
49
TB + HIV Drugs
- 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)
