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General ID 2019 > HIV resistance testing, ART > Flashcards

HIV resistance testing, ART Flashcards

1
Q

what is a genotypic resistance test?

A

mutations in viral genes

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2
Q

what is a phenotypic test?

A

describes growth of virus in the presence of anti - HIV drugs

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3
Q

what does M184 V mean?

A

Methionine (wild-type amino acid) is replaced with valine (mutant amino acid) at the 184 codon position

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4
Q

when do you obtain a HIV genotype only? (2 answers)

A

(1) obtain HIV genotype before ART started (2) following failure of 1st or 2nd regimen, get genotype to determine the optimal next regimen

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5
Q

When do you obtain a HIV genotype and HIV phenotype resistance testing?

A

Following failure of 3rd and subsequent regimen

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6
Q

If there is a discordance between genotype and phenotype, which one do you use?

A

genotype result is more sensitive

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7
Q

Name the NRTIs and abbreviations? (7)

A
  • Zidovudine (ZDV/AZT)
  • Didanosine (ddI)
  • Stavudine (d4T)
  • Lamivudine (3TC)
  • abacavir (ABC)
  • emtricitbine (FTC)
  • tenofovir (TDF/TAF)
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8
Q

Name the NNRTIs? (5)

A
  • Nevirapine (NVP)
  • delaviridein (DLV)
  • Efavirenz (EFV)
  • etravirine (ETR)
  • *Rilpivrine (RPV)**
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9
Q

Name the entry inhibitors? (3)

A
  • Enfuviritide (T-20, fusion inhibitor)
  • maraviroc (MVC, CCR5 antagonist)
  • lbalizumab (CD4 post attachment inhibitor)
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10
Q

Name the integrase inhibitors? (4)

A
  • raltegravir (RAL)
  • elvitegravir (EVG)
  • dolutegravir (DTG)
  • bictegravir (BIC)
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11
Q

What is the recommend initial ART regimen?

A

These are 2 NRTI + 2 integrase inhibitor regimens

  • bictegravir/TAF/emtricitabine (biktarvy + Descovy)
  • dolutegravir/abacavir/lamivudine (if HLAb507 negative) - Triumeq
  • Dolutegravir + (tenofovir/emtricitabine) - Tivicay + Descovy/Truvada
  • raltegravir + tenofovir/emtricitabine - Isentress + Descovy/Truvada
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12
Q

what are the alternatives to the 2NRTI + integrase inhibitor regimen basics?

A
  1. Boosted PI + 2NRTIs
  2. NNRTI + 2 NRTIs
  3. INSTI + 2NRTIs
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13
Q

what are the two NNRTI based alternative regimen?

A
  • efavirenz (EFV)/tenofovir(TAF/TDF)/emtricitabine (FTC) (Sustiva + Descovy/Truvada = Atripla (EFV/TDF/FTC))
  • rilpivirine/tenofovir/emtricitabine (Odefsey (TAF)/Complera (TDF))
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14
Q

what are the PI based alternative regimen?

A
  • darunavir (DRV/Prezista)/cobicistat (Prezcobix - DRV+Cobi))+ tenofovir/emtricitabine (Descovy/Truvada)
  • atazanavir/ritonovair (or with cobicistat) + tenofovir/emtricitabine (Cimduo (TDF/3TC)
  • darunavir/ritonavir (or/cobicistat) + abacavir (ABC/Ziagen)/lamivudine (Epivir/3TC) (ABC/3TC = Kivexa)
  • atazanavir/ritonavir (or/cobicistat) + + abacavir/lamivudine
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15
Q

what regimen can you use if you can’t use NRTIs (2)

A
  1. DRV-r + RAL BID (If CD4>200, VL<100K) (Preziesta + Isentress (II + NNRTI)
  2. DTG (DTG/Tivicay) + RPV (RPV/Edurant) = (II + PI) = JULUCA
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16
Q

what toxicity and dosing associated with tenofovir/emtricitabine (Descovy/Truvada)?

A

renal and bone toxicity; 1 tab daily

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17
Q

what toxicity/things you need to know associated with abacavir/lamivudine (ABC/3TC- Kivexa)?

A

5-8% HSR (check hla55701). 1 tab qdaily; recommended only with dolutegravir?

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18
Q

what toxicity and dosing scheduleassociated with zidovudine/lamivudine(AZT/3TC - combivir)?

A

1 tab BID; GI, anemia, lipoatrophy; no longer recommended

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19
Q

what toxicity and dosing schedule associated with efavirenz/Sustiva (NNRTI)?

A

CNS toxicity (50%), rash, teratogenicity, q daily.

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20
Q

what toxicity and dosing scheduleassociated with rilpivirine?

A

q daily; not well absorbed with PPI

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21
Q

what toxicity and dosing scheduleassociated with nevirapine?

A

no longer recommended, hepatotoxicity, hypersensitivity

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22
Q

what toxicity and dosing schedule associated with darunavir/ritonvair or/cobicistat?

A

qd or bid if no prior resistance, skin rash. OK in pregnancy.

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23
Q

what toxicity and dosing schedule associated with atazanavir/ritonavir or/cobicistat?

A

q daily, increased indirect bilirubin, GI; need to avoid PPI, kiney stones (uncommon), ok in pregnancy

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24
Q

what toxicity and dosing schedule associated with lopinavir/ritonavir?

A

BID/QD, diarrhea and increased lipids

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25
Q

What’s in atripla?

A

efavirenz (NNRTI of EFV)+ TDF/FTC

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26
Q

what is in biktarvy?

A

bictegravir (integrase inhibitor BIC) + TAF/FTC (Descovy)

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27
Q

what is in complera?

A

rilpivirine (NNRTI/RPV/Edurant) + TDF/FTC (Truvada)

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28
Q

what is in genvoya?

A

Elvtegravir (Integrase inhibitor EVG/Cobi) + TAF/FTC (Descovy)

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29
Q

what is in odefsey?

A

Rilpivirine (NNRTI of RPV/Edurant) + TAF/FTC (Descovy)

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30
Q

what is in stribild?

A

elvitegravir (integrase inhibitor of EVG) + Cobi + TDF/FTC (Truvada)

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31
Q

what is triumeq?

A

Dolutegravir (integrase inhibitor of DTG) + abacavir/lamivudine (kivexa)

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32
Q

what is juluca?

A

Dolutegravir (DTG) + rilpivirine (RPV) - II + NNRTI

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33
Q

what is in descovy?

A

TAF/FTC

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34
Q

what is in epizicom?

A

abacavir (ABC) + lamivudine (3TC)

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35
Q

what is in trizivir?

A

abacavir (ABC) + zidovuine(AZT/ZDV) + lamivudine (3TC)

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36
Q

what is in viread?

A

TDF

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37
Q

what is in ziagen?

A

abacavir (ABC)

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38
Q

what is in norvir?

A

ritonavir (RTV)

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39
Q

what is in prezista?

A

darunavir (DRV)

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40
Q

what is in tivicay?

A

dolutegravir (DTG)

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41
Q

what is in isentress?

A

raltegravir (RTG)

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42
Q

what drugs do you need to worry about in ART with hepatitis?

A

(NNRTIs+ PIs) especially nevirapine with women with CD4>250 and men with CD4>400

43
Q

what drugs do you need to worry about in ART with HSR?

A
  1. NRTI (abacavir/Ziagen)
  2. NNRTI: nevirapine, etravirine
44
Q

what drugs do you need to worry about in ART with steven johnson’s syndrome?

A

NNRTIs: nevirapine, etravirine

45
Q

what drugs do you need to worry about in ART with pancreatitis?

A

NRTI: didanosine, stavudine

46
Q

what drugs do you need to worry about in ART with teratogenicity?

A

NNRTI efavirenz (Sustiva/EFV)

Integrase Inhibitors: dolutegravir - Tivicay/DTG - (NTD)

47
Q

what drugs do you need to worry about in ART with kidney stones?

A

indinavir>atazanavir

48
Q

what ART is associated with decreased bone mineral density ?

A

TDF

49
Q

what drugs do you need to worry about in ART with CNS issues?

A

efavirenz, integrase inhibitors?

50
Q

what drugs do you need to worry about in ART with anemia, neutropenia?

A

NNRTI: Zidovudine

51
Q

when do you need to change ART therapy?

A

VL>200

52
Q

what drug/effect on other NRTI’s associated with M184V?

A
  • 3TC, FTC;
  • decease susceptibility to ABC,ddI (clinically insignificant0,
  • delayed TAMS and increase susceptibility to AZT, d4T, TDF
53
Q

what drug/effect on other NRTI’s associated with TAMs (thymidine-analog mutations)?

A
  • selected by AZT, d4T;
  • Decrease susceptibility to all NRTIs based on TAMS
54
Q

what drug/effect on other NRTI’s associated with 151M, 69SSS?

A
  • selected by AZT/ddI, and ddI/d4T
  • resistance to all NRTIs
  • T69ins: TDF resistance
55
Q

what drug/effect on other NRTI’s associated with 65R?

A
  • Selected by TDF, ABC, ddI
  • variable decrease susceptibility to TDF, ABC, ddi (and 3TC, FTC)
  • Increase susceptibility to AZT
56
Q

what drug/effect on other NRTI’s associated with 74V?

A
  • Selected by ABC, ddI
  • decrease susceptibility to ABC, ddi
  • Increase susceptibility to AZT, TDF
57
Q

what drug/effect on other NRTI’s associated with 44D,118I

A
  • increase NRTI resistance (with 41/210/215 pathway)
58
Q

What mutation associated with K103N?

A

Efavirenz (EFV) and NVP

59
Q

What mutation associated with Y181C?

A

nevirapine (NVP) and other NNRTIs

60
Q

Rilpivirine failure is associated with which mutations?

A

E138K, K101E, and/or Y181C and cosnequently, resistance to ALL

61
Q

which mutation and drugs confers resistance to one PI?

A

I50L alone confers resistance to atazanavir (ATV)

62
Q

what is the primary mutation to dolutegravir?

A

R263K

63
Q

what are teh most common mutation associated with raltegravir and elvategravir?

A
  • q148R and N155H most common.
  • E92Q less common.
  • E681 and V increase resistance but not sufficient alone
64
Q

In the US, what is the prevalence of any baseline (pre-Rx) resistance mutations (%?)?

A

5-15%

65
Q

how would you treat active TB in a patient with HIV?

A

treat the same as without TB.

66
Q

what time period do you treat a patient with TB for CD4<50?

A

within 2 weeks of TB rx

67
Q

what time period do you treat a patient with TB with ART for CD4>50 with severe clinical disease?

A

Start ART within 2-4 weeks of TB rx

68
Q

what time period do you treat a patient with TB for with ART for CD4>50 without severe clinical disease?

A

8-12 weeks of TB rx

69
Q

what time period do you treat a patient with ART for MDr or XDR TB?

A

within 2-4 weeks of TB rx

70
Q

what do you need to consider when choosing an ART regimen in a patient being treated for TB?

A

TB meds including rifamycin (rifampin), which:

  • significantly decrease all PIs - cannot use together
  • decrease RAL and DTG concentrations (need to increase RAL and DTG concentrations)
  • decrease NNRTI concentrations
  • Rifabutin better than rifampin since more managlbe drug interactions with PIs
71
Q

which ART drugs have activity against HBV?

A

Lamivudine (3TC), emtricitabine (FTC) and tenofovir

72
Q

what is the optimal regimen for treatment of HIV-HBV co-infection?

A
  • 2 active agents against HBV,
  • 3 active agents against HIV
  • (ex.TDF/FTC + 3rd drug)
73
Q

what special considerations do you need to think about for antiretrovirals in pregnancy?

A
  • No increase risk of birth defects
  • perform drug resistance testing if VL>500-100 and adjust regimen
  • Standard ART regimens
74
Q

If a patient is near delivery and has HIV/AIDs, what do you need to think about?

A

Near delivery, if HIV RNA>1000 or unknwon, use intravenous zidovudine and recommend C-section at 38 weeks

75
Q

what is the preferred regimen and alternative regimen for NRTI’s ART in pregnancy?

A

NRTIs!

Preferred is:

  • abacavir/lamivudine
  • TDF/FTC

Alternative is:

  • Zidovudine/lamivudine
76
Q

which NRTI ART agents are not recommended and why?

A

Not recommended:

  • Zidovudine/lamivudine/abacavir (3NRTIs)
  • Didanosine (toxicity)
  • Stavudine (toxicity)
  • TAF (insufficient data)
77
Q

which NNRTI’s are recommended and not recommended in pregnancy?

A

Alternative:

  • Efavirenz (screen for depression)
  • Rilpivirine (not with baseline VL>100K or CD4<200)

Not recommended

  • Etravirine (not for treatment -naive)
  • Nevirapine (toxicity, need for lead in dosing, low barrier to resistance)
78
Q

which PI ARTs are preferred and alternative in pregnancy?

A

Preferred

  • Atazanavir/ritonavir
  • darunavir/ritonavir (use BID)

Alternative

  • lopinavir/ritonavir (use BID)
79
Q

whcih integrase inhibitors preferred and alternative and not recommended in pregnancy?

A
  • Raltegravir (preferred)
  • dolutegravir (NT defects if taken during conception but not later in pregnancy)
  • Bictegravir (insufficient data)
  • elvitegravir combinations (not recommended)
80
Q

what antiretrovirals/testing timeline do you use for occupational PEP?

A

4 weeks of rx for recognized transmission risk:

  • start ASAP (within 72 hours)
  • TDF/FTC/DTG (not for early pregnancy or sexually active not on birth control) or raltegravir
  • F/u within 72 hours
  • adjust regimen based upon source patient resistance
  • Testing (baseline, 6 weeks, 12 weeks, 6 months with standard HIv ab)
  • Testing (baseline, 6, weeks, 4 months if new HIV ab/p24 test used)
81
Q

who do you treat for PEP for non-occupational exposure?

A
  • Presentation within 72 hours with substantial risk exposure from HIV + source = recommended)
  • Presentation <72 hours with substantial risk exposure from source with unknown HIV status - case by case basis
  • Presentation >72 hours or no substantial risk exposure - not recommended
82
Q

How do you test and treat for non-occupational PEP?

A
  • Testing: rapid HIV Ag/Ab test, if result not availble, start PEP
  • Treatment - 4 weeks
    • Preferred: TDF/FTC/DTG (not in pregos, sex active w/o birth control) or raltegravir
    • Alternative: TDF/FTC + darunavir/ritonavir
83
Q

What do you need to do before starting PrEP?

A
  • Document HIV ab negative and r/o acute infection withi na week of starting medication
  • Docuemtn CrCl>60
  • Screen for STIs and HBV infection
84
Q

what medication do you give for PrEP?

A

TDF/FTC 1 PO daily x 90 days

85
Q

Patient is on treatment for PrEP. what do you need to test/do?

A
  • HIV testing q3 months
  • check Crcl q 6 months
  • risk reduction, protection, STI
  • evaluate need for PrEP
86
Q

which drugs do you need to worry about elevated cardiovascular risk? Which can have a beneficial risk?

A
  • Elevate Lipids: Cobi or RTV regimens
  • high MI risk: Abacavir (ABC)- SMART/INSIGHT trial
  • Decrease lipids: TDF-Regimens
87
Q

which drugs do you need to worry about renal function and why?

A
  • TDF can cause renal tubular dysfunction like Fanconi with pre-existing renal disease, low body weight, longer tx duration.
  • Boosted ATV/R and LPV/R associated with greater decrease in renal function compared to NNRTI
  • Cobi and DTG can cause decreased tubular excretion of creatinine and cause a slight increase.
88
Q

Name the PIs and adverse effects?

A
  • Prezcobix (Darunavir + cobi)
  • Preziesta (darunavir) - Rash
  • Reytaz (atazanavir) - Elevated bilirubin
  • All: hyperglycemia, hyperlipidemia, lipodystorphy, N/V/D,
89
Q

adverse effects associated with NRTRIs in general and specific?

A
  • All: Lactic acidosis, hepatic steatosis, N/V/D
  • Abacavir: HLAb-5701 associated fatal hypersensitivity
  • Emtrictiabine (FTC): Skin hyperpigmentation
  • Tenofovir (fanoci renal dysfunction
  • Zidoviduine: anemia, neutropenia, fatigue
90
Q

Adverse events associated with NNRTIs?

A
  • All: Nausea, vomiting, headache
  • Efavirenz: skin hyperpigmentation
  • Etarvirine: LFT elevation, dyslipidemia, rash
  • Rilpivirine: rash
91
Q

adverse events associated ISTIs?

A

All: headache, N/V/D

Raltegravir: CPK elevation, fatigue, rash

92
Q

Name the HIV drugs that can be crushed or chewable?

A
  • Darunavir
  • Dolutegravir
  • Etravine
  • Lamivudine
  • TDF
  • TAF/FTC
  • TDF/FTC
  • Zidovuine/lamivudine
  • Raltegravir (chewable)
93
Q

which HIV drugs have liquid form?

A
  • Abacavir
  • Darunavir
  • FTC
  • 3TC
  • Raltegravir
  • Ritonavir
94
Q

which are the basic NRTI mutations?

A
  • M184V - FTC/3TC,ABC
  • K65R - FTC/3TC,ABC, Tenofovir
  • T69INS - All NRTIs
95
Q

which are the basic NNRTI mutations?

A
  • K103n - Efavirenz, Nevirapine
  • Y181C- All NNRTIs
  • Y188L - All NRTIs
96
Q

which are the basic INSTI mutations?

A
  • Q148H/R/K
  • N155H
  • E92Q
  • G140S/A/C
97
Q

draw the typical course of a HIV infection.

A
98
Q

draw virologic and serologic time course of testing graph.

A
99
Q

what are the non-infectious neurologic complications of HIV (4)

A
  1. HIV-associated neurocognitive disorders (HAND syndrome) include changes in memory, concentration, attention, and motor skills that cannot be attributed to an alternative cause
  2. Central nervous system (CNS) viral escape syndrome occurs when there is HIV replication in the CNS leading to neurocognitive symptoms in patents who are virally suppressed on ART. Most patients have viral drug resistance in the CSF.
  3. Distal symmetric peripheral neuropathies (DSPN) is a symmetric, bilateral pattern of diminished sensation and reflexes typically starting in the toes spreading proximally in the lower extremities.
  4. Vascular myelopathy is a vacuolization of the lateral and posterior columns of the thoracic spine leading to a spastic paraparesis, loss of sensation, and urinary incontinence. The pattern is very similar in presentation to myelopathy from vitamin B12 deficiency.
100
Q

what are the dermatologic manifestation of HIV? (7)

A
  1. Acute HIV exanthem and enanthem is typically a non-pruritic rash involving the upper trunk, proximal limbs, and potentially the palms and soles. It can be seen in up to half of patients with acute infection. It typically resolves in 1–2 weeks
  2. Seborrheic dermatitis - It is described as an eruption on the scalp and central areas of the face
  3. Eosinophilic folliculitis is typically described in patients with advanced disease and is a pruritic skin eruption of follicular papules or pustules, predominantly located on the scalp, face, neck, and upper chest
  4. Psoariasis - similar silvery, plaque-like appearance with more wide distribution on extensor surfaces as well as potentially involvement of the palms, soles, axilla, and groin with associated arthritis. Treatment may include potent topical steroids, ultraviolet light with or without tar, immunosuppressives (e.g., methotrexate), and retinoids.
  5. Xerosis or dry skin may be very severe in patients with advanced disease on presentation.Risk factors include excessive bathing, and treatment includes emollients and topical corticosteroids
  6. Drug reactions to trimethoprim–sulfamethoxazole (TMP–SMZ) are more common in persons infected with HIV. more severe manifestations may include exfoliative erythroderma, fixed-drug eruption, erythema multiforme, and toxic epidermal necrolysis
  7. KS
101
Q

what malignancies associated with HIV and the infection? (4)

A
  1. Kapsoi sarcoma (HHV8) - Doxorubicin/danorubicin
  2. multi-central castlemans disease (HHV8) - lymphoproliferative disorder characterized by angiofollicular lymph node hyperplasia manifests with systemic symptoms including fever, fatigue, generalized lymphadenopathy, hepatosplenomegaly, and pancytopenia. Tx - Rituximab
  3. NHL - (HHV8 and/or EBV) w/o BCL-2 activation.
  4. Primary Effusion lymphoma - rare type of NHL associated HHV8. grows in body cavities (pleural, pericardial, and peritoneal) as lymphomatous effusions that are not associated with a mass. Diagnosis is made based on cytology of the pleural fluid. In contrast to NHL, it lacks alterations to the genes bcl2, bcl6, ras, and p53. It has a very high mortality rate.
102
Q

what are the AIDS related lymphomas?

A

Diffuse large B cell lymphoma: tumors consisting of large, atypical lymphoid patterns that express pan-B cell antigens.

Burkitt’s lymphoma: have a “starry-sky” pattern with prominent cytoplasmic vacuoles in monomorphic, medium-sized cells with multiple nuclei.

Plasmablastic lymphoma: rare lymphoma that typically presents in the oral cavity and is driven by HHV-8 infection. They are very aggressive and have a poor prognosis.

Hodgkin lymphoma - Reed sternberg cells, among small lymphocytes, eosinophils, neutrophils, histiocytes, and plasma cells

103
Q
A

General ID 2019 (19 decks)

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