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HIV Flashcards

1
Q

CNS Viral Escape syndrome

A

occurs w/ HIV replication in CNS → neurocognitive sx in pts who are virally suppressed

  • measurable HIV RNA in the CSF
  • most develop resistance - avoid efavirenz
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2
Q

ART a/w bone mineral dysfunction

A
  • (Note: HIV indep a/w lower BMD d/t proinflammatory cytokines increasing osteoclastic activity)
  • TDF - higher PTH and lower Vit D
    • also a/w fanconi (leads to hypophos and osteomalacia)
  • efavirenz - Vit D def
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3
Q

infectious causes of normocytic anemia in advanced HIV

A

chronic infection w/ parvo B19, MAC

**remember diminised erythopoiesis d/t HIV infection

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4
Q

infections a/w acalculous cholecystitis and AIDS cholangiopathy

A

CMV

crypto

(though, primarily non-infectious)

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5
Q

How the boards might test for IRIS. Pt started on ART, then develops…

  • unrecognized lymphadenitis
  • unrecognized meningitis
  • unrecognized retinitis
  • new skin lesions
  • pulmonary infiltrates
  • new focal neuro findings
  • new transaminitis
A
  • TB, MAC, fungi
  • crypto
  • CMV
  • KS
  • PJP, fungi, TB
  • crypto meningitis w/ ICP
  • untreated HBV
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6
Q

Pathogens commonly a/w IRIS

A
  • MAC
  • TB
  • crypto

among others: CMV retinitis, HBV, mucocutaneous HSV and VZV, PJP, histo, KS

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7
Q

When to DC MAC therapy

A
  • CD4>100 x6mos
  • asx
  • tx > 12mos
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8
Q

MAC therapy in HIV

A

clarithro (or azithro) + ethambutol

+rifabutin if severe disease

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9
Q

Primary prevention of toxo

A

Indication: +IgG and CD4<100

  • 1st choice - TMP/SMX DS QD
  • Alt - dapsone-pyrimethamine, atovaquone + pyrimethamine
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10
Q

Preferred and alt regimens for CNS toxo

A
  • Preferred: sulfadiazine + pyrimethamine + leucovorin
  • Alt: bactrim (HD), clinda+pyrimethamine, atovaquone +/- pyrimethamine
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11
Q

empiric dx of CNS toxo (most pts dx empirically)

A
  • compatible CT/MRI
  • CD4<100
  • toxo IgG+
  • not on bactrim ppx
  • response to therapy w/in 2wks
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12
Q

CNS mass lesions

A
  • If <100: toxoplasma, lymphoma
  • TB
  • fungal
  • nocardia
  • bacterial
  • syphilis
  • kaposi
  • glioblastoma
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13
Q

mechanisms of renal pathway inhibition by tenofovir, cobi, BIC, DTG

A
  • tenofovir - inhibits OAT1/OAT3 in proximal tubule - inhibits secretion of Cr
  • cobi - inhibits MATE1 - inhibits secretion of Sc at PT
  • DTG, BIC - inhibit OCT2 at PT
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14
Q

mechanism and tx for HIV-assoc ITP

A

HIV coats plts → attracts anti-HIV Abs which leads to removal of plts by spleen

tx w/ ART - lowers VL → plts rise to near nml levels

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15
Q

high-grade proteinuria

nml-large kidneys

NO EDEMA

rapid progression to ESRD

A

HIVAN

most effective prevention = ART (virus infects the glomerulus itself)

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16
Q

pt with HIV + PJP on tx w/ Bactrim

O2 sat gap: pulse ox < ABG O2

A

2/2 methemoglobinemia from bactrim

  • Fe2 → Fe3 which blocks binding of O2
  • Tx: dc offending agent, given methylene blue (when metHgb level >30%)
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17
Q

hypophos

renal glucosuria

hypouricemia, aminoaciduria

(don’t need to have all present at once)

A

T2 RTA (fanconi) - generalized prox tubule dysfunction

d/t tenofovir

dc tenofovir - can take mos to recover

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18
Q

nucleoside-induced myopathy (ragged red fiber disease)

A

zdv-induced

chronic (not acute presentation)

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19
Q

RF for AVN in HIV

A
  • h/o IDU
  • increased duration of HIV (likely received older regimens - PIs)
  • low CD4
  • elevated lipids
  • steroid use
  • EtOH use
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20
Q

PrEP recommendations (rx and f/u)

A

TDF/FTC daily

  • HIV testing q3mos, CrCl q6mos
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21
Q

PEP recs for occupational exposure

A

testing (bl, 6wk, 12wk, 4-6mos)

TDF/FTC + DTG (RTG if F in early pregnancy or sexually active and not on BC)

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22
Q

Preferred INSTI in pregnancy

A
  • RTG, DTG (not at conception or in 1st trimester, but later ok)
  • BIC w/ insufficient data
  • Not rec: elvitegravir (b/c of booster)
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23
Q

Preferred PIs in pregnancy

A
  • atazanavir/r, DOR/r (BID)
  • Alt: loinavir/r (BID)

Not rec (d/t pill counts and tox in older regimens): cobi (inexperience in pregnancy), indinavir, fos, nelfinavir, tipranavir

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24
Q

Preferred NNRTIs during pregnanct

A

None. All are alt options

  • EFV - screen for depression. Birth defects in monkeys (not humans)
  • Rilpivirine - NOT with VL > 100K or CD4<200

NOT rec: etravirine, nevirapine (toxicity, low barrier to R)

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25
Q

Preferred NRTI skeleton with pregnant

A
  • ABC/3TC, tenofovir/FTC or 3TC
  • Alt: zidovuine/3TC

NOT rec: 3 NRTIs, didanosine, stavudine

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26
Q

What to give in pregnancy if near delivery and when?

A

IV zidovudine if RNA >1000 or unknown

rec c/s @ 38wks

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27
Q

Which ART also has HBV activity?

A
  • lamivudine
  • FTC
  • tenofovir

need 2 rx when tx HBV (3 for HIV) =tenofovir + [3TC or FTC] + 3rd rx

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28
Q

TB-HIV

Important rx to ensure is used:

A

a rifamycin

  • rifabutin preferred
  • rifampin - significantly decreases all PIs, as well as DTG (need to incr DTG to 50 BID), and NNRTI (rec EFV 600mg daily)
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29
Q

if ART started prior to genotype, what should you use?

A

BIC, DOR/c, or DTG + TAF/FTC

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30
Q

Chronic/Longer Term SEs w/ ART

  • CVD
  • kidney stones
  • metabolic (glucose, lactate, lipids)
  • morphologic (lipoatrophy, lipohypertrophy)
  • peripheral neuropathy
  • proximal RTA (Fanconi)
  • wt gain
A
  • ?ABC, PIs (exc atazanavir)
  • indinavir > atazanavir
  • older PIs (stavudine, esp)
  • LA - stavudine, zidovudine; LH - older PIs
  • stavudine, didanosine
  • TDF
  • BIC, DTG
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31
Q

Acute/Early SEs w/ ART:

  • GI
  • anemia, neutropenia
  • BMD
  • CNS
  • fatigue
  • indirect hyperbili
  • rash
A
  • zidovudine, didanosine, TDF, PIs (?all ART)
  • zidovudine
  • TDF
  • efavirenz
  • zidovuine
  • atazanavir, indinavir
  • NNRTIs
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32
Q

ART s/e SJS

A

nevirapine, etravirine (NNRTIs)

also darunavir (PI)

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33
Q

ART s/e pancreatitis

A

older nucleoside analogs: didanosine, stavudine

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34
Q

ART s/e lactic acidosis

A

older nucleoside analogs: didanosine, stavudine

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35
Q

ART s/e hepatitis

A

think NNRTIs, PIs

*nevirapine - F w/ CD4>250; M w/ CD4>500

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36
Q

Cytochrome P450 3A4 inhibitors (classes)

A

PIs (ritonavir = most potent; also cobi)

*increases level of other metabolized rx

Concern w/: rifampin, rifabutin, azoles, antiseizures, statins, midazolam, HCV rx

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37
Q

Cytochrome P450 3A4 inducers

A

NNRTIs (EFV, ETR, NVP, RPV. Not DOR)

**decrease levels of other metabolized drugs

Concern w/: rifamycins, azoles, antiseizure rx, statins, HIV PIs, maraviroc)

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38
Q

Toxicities and considerations of atazanavir/r or c (PI)

A
  • elevated indirect bilirubin
  • GI
  • avoid PPI
  • kidney stones (uncommon)
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39
Q

Toxicities and considerations of darunavir/r or c (PI)

A

preferred over atazanavir

skin rash (rare)

EM, SJS, TEN have occurred

*activity vs PI-R strains

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40
Q

Toxicities and considerations of rilpivirine (NNRTI)

A

not well absorbed w/ PPI

_***not for RNA >100k or CD4<200_

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41
Q

Toxicities and considerations of EFV (NNRTI)

A
  • CNS tox - neuropsych (vivid dreams, hallucinations)
  • suicidality, depression (don’t use if h/o)
  • rash
  • suicidality
  • *TDF/TFC/EFV (1 pill daily)
42
Q

Toxicities and considerations of doravirine (NNRTI)

A
  • decreased CNS tox c/w EFV
  • decreased lipid abnormalities

*TDF/FTC/DOR = 1 pill daily

43
Q

Toxicities and considerations of zidovudine (NRTI)

A

GI, anemia, lipoatrophy

44
Q

Toxicities and considerations of ABC/3TC (NRTI combo)

A

*recommended w/ DTG only

  • hypersensitivity reaction
  • ??increased risk of MI (w/ ABC)
45
Q

Toxicities and considerations of tenofovir

A

renal, bone (w/ TDF)

46
Q

What to consider when ABC, TAF/TDF can’t be used

A
  • DTG/3TC (except VL>500k, HBsAg+)
  • DRV/r + RTG (if RNA < 100K and CD4>200)
  • DRV/r+3TC
47
Q

circumstances in which you can’t start with DTG/3TC

A
  • RNA > 500k (lamivudine)
  • HBVsAg+ (only has one active HBV agent)
  • no resistance results (really only used as switch in well-controlled pt)
48
Q

which ART can you not use with VL>100k? >500k?

A

>100k = rilpivirine (or ABC)

>500k = lamivudine

49
Q

Detecting HIV Infection

A

Screening: 4th ELISA (Ag/Ab), qual HIV RNA

Supplemental/Confirmation = highest specificity; multispot/geenius (confirms HIV-1 or -2)

50
Q

For reference:

HIV Detection Timing

51
Q

Other conditions where PJP is common

52
Q

tox of atovaquone

A
  • absorption if low-fat diet
  • rash
  • N/V/D
  • increased LFTs
53
Q

Tox of IV pentamidine

A
  • Hypotension - rate-related
  • Increased SCr
  • Increased amylase
  • Hypoglycemia early in course! (a/w increased SCr, may occur days-wks post-tx)
  • Torsades de Pointes
54
Q

Tox of TMP/SMX

A
  • decreased WBC and plts
  • increased LFTs, SCr
  • “sepsis”
  • Hyperkalemia (TMP) - pumps out TMP instead of K
  • cross-reactivity with dapsone!
55
Q

Which tx for PJP can lead to torsades?

56
Q

Reasons to deteriorate during PJP Tx

A
  • fluid overload: iatrogenic, cardiac, renal failure (sulfa-, pentam-related)
  • anemia
  • methemoglobinemia (dapsone, primaquine)
  • PTX
  • unrecognized concurrent infection
  • IRIS
57
Q

Average time to clinical improvement in PJP

A

4-8 days (rads obviously lags clinical improvement)

58
Q

Therapy for PJP

A
  1. TMP/SMX
  2. Alt: parental pentam, atovaquone, clinda/primaquine
    • ?Adjuvant steroids
60
Q

Dx of PJP PNA

A
  • Methenamine silver
  • Giemsa
  • IF = green org on black (“honeycomb cluster”)
  • Bx H&E: foamy alveolar infiltrate
  • PCR - highly sensitive in BAL (NOT in blood)
  • Beta-glucan - sensitive serological test, but not specific. Useful when high suspicion but BAL/sputum not feasible
61
Q

Very uncommon manifestations of PJP (primarily pulmonary infection)

A
  • ocular
  • pulmonary blebs, cavitation, PTX
  • splenic disease
  • digit necrosis
62
Q

rarely cause pulm dz in HIV (even if isolated from secretions)

A

CMV

MAC

HSV

63
Q

Uncommon etiologies of HIV-assoc Pulm d/o (less likely to be answers on boards, but need to consider)

A
  • aspergillus
  • histo/cocci
  • staphylococci
  • toxo
  • lymphoma
  • KS
64
Q

Comorb that predispose to pneumococci which are over-represented in HIV

A
  • opioid use d/o, EtOH, tobacco
  • lack of immunization
  • COPD, CHF, obesity
  • MRSA colonization
  • liver disease
65
Q

Approach to Dx of PNA in pts with HIV:

  • onset >3 days vs <3 days:
  • afebrile:
  • purulent sputum vs scan sputum:
  • PE normal vs consolidative:
A
  • >3 days (subacute): PJP, TB
  • <3 days: bacterial or other viral
  • afebrile: think neoplasm
  • purulent: bacterial
  • scant sputum: PJP, TB, viral
  • normal PE: think PJP. Consolidative: think bacterial
66
Q

Common causes of HIV-assoc Pulm d/o

A
  • pneumococcus
  • hemophilus
  • PJP
  • TB
  • atypicals/viral
67
Q

Secondary OI ppx

(what, when)

A
  • PJP - untill CD4>200 x3mos
  • Toxo - until CD4>200 x6mos + adeq clinical response
  • MAC - until CD4>100 x6mo + 12mo minimum + adeq clinical response
  • CMV - until CD4>100 x3-6mo + adeq clinical response
  • Crypto - until CD4>200 x6mo + adeq clinical response
  • Histo (?) - some say w/ itra until CD4>150
  • Cocci - fluc until CD4>250 and fully suppressed VL
68
Q

When/What for Primary Ppx

  • PJP
  • Toxo
  • Cocci
  • MAC
A
  • PJP: CD4<200; dc when CD4>200 x3mos
  • Toxo: CD4<100 w/ +toxo IgG; dc when CD4>200 x3mos
  • Cocci: CD4<250 w/ +cocci IgM/IgG (tested 1-2x/yr). Tx w/ fluc 400mg QD until CD4>250+fully suppressed VL
  • MAC: none required
69
Q

When to start ART following OIs

  • list exceptions
A

W/in 2 weeks!

Exceptions

  • TB: CD4<50 - w/in 2wks; CD4>50 - 8wks
  • crypto meningitis - 4-6wks after starting AMB (sooner if mild and CD4<50, later if severe)
  • Untreatable OIs (PML, cryptosporidiosis) - start ART immediately
70
Q

Clinical Indicators of Immunosuppression

A
  • OP candidiasis
  • Hairy Leukopenia
  • Disseminated VZV
71
Q

2 skin conditions often confused with each other

A

KS

Bartonella (bacillary angiomatosis)

72
Q

What two PJP/toxo ppx rxs cross-react (don’t use with allergy to one)

A

Dapsone and sulfonamides

(Pentam doesn’t have toxo)

73
Q

N155H

Q148H/R/K

Y143C

A

R to RAL, EVG

use DTG BID if able

74
Q

R263K

75
Q

mutation w/ highest level of R to elvitegravir

76
Q

I50L

A

resistance to atazanavir

**most pts w/ failure on 2 NRTI + bPI have NO PI mutations

***requires multiple mutations

77
Q

Rilpivirine failure

A

a/w E138K, K101E, Y181C –> ALL NNRTIs lost

78
Q

basic NNRTI R knowledge

A
  • older NNRTIs (efavirenz, nevirapine) = LOW barrier to resistance with complete cross-reactivity
  • newer NNRTIs (etravirine, rilpivirine, doravirine) - higher barriers to resistance
79
Q

Y181C

A

nevirapine (NNRTI)

80
Q

K103N

A

efavirenz and nevirapine (NNRTI)

***retains susc to etravirine and rilpivirine

81
Q

74V

Selected by:

Effect:

A

selected by ABC, ddI

  • decr susc to ABC, ddI
  • increased susc to AZT, TDF
82
Q

K65R

Selected by:

Effect:

A

selected by TDF, ABC, ddI

  • High-level R to tenofovir
  • variable decr susc to ABC, ddI as well as 3TC, FTC
  • increased susc to AZT
83
Q

151M, 69ins

Selected by:

Effect:

A
  • selected by AZT/ddI, ddI/d4T
  • resistance to ALL NRTIs
  • T69ins = TDF R
84
Q

TAMS

Selected by:

Effect:

A

selected by AZT, d4T

  • decreased susc to all NRTIs based on # of TAMS
  • R w/ 41/210/215 (Type 1 TAMS) > 67/70/219 pathway (Type 2 TAMS)
85
Q

M184V

Selected by:

Effect:

A

selected by 3TC, FTC

  • loss of susc to 3TC, FTC
  • dec susc to ABC
  • delayed TAMS

**increased susc to AZT, d4T, tenofovir

86
Q

N155H

Q148H/R/K

Y143C

87
Q

spontaneous PTX

or CXR w/ b/l butterfly-pattern GG intersitial infiltrate (classic, but not commonly seen)

88
Q

Dx tests for PJP

A
  • Ddx = visualization of org on respiratory specimen (silver, Geimsa, DFA)
    • ​induced sputum - 60% sens
    • bronch w/ BAL or bronch bx - >90-95% sens
  • Fungitell - elevated, but non-specific
    • high NPP
89
Q

Diagnostics for histo

A
  • Def Dx = isolation in cx
  • histopath = 2-4um budding intracellular yeast
  • histo urine/serum Ags highly sensitive (but cross-react w/ other dimorphic fungi)
  • will see marked elevation of LDH and ferritin (non-specific)
90
Q

Advanced HIV

person from SE Asia

disseminated, multiorgan disease

characteristic skin lesions w/ prediliction for liver (marked LFT elevation)

A

think talaromycosis

tx w/ LAMB x2wks, then itra

91
Q

Preferred ART regimen with TB co-infection

A

2 NRTI + efavirenz (excellent outcomes, low rates of tox)

can use RTG, DTG as well (may need to increase doses w/ rifamycin-containing TB regimen)

TAF should NOT be used w/ any rifamycins

  • if PI or NNRTI necessary - use rifabutin instead of rifampin
92
Q

CD4 <50

fevers, night sweats, wt loss, chronic D, HSM, diffuse LAD

A

consider disseminated MAC

93
Q

tx of bacillary angiomatosis (or peliosis hepatitis)

A

erythromycin or doxycycline x3+ mos

94
Q

diarrheal illness in advanced HIV (and tx)

  • 4-6um
  • 1-5 um
  • 22-23 x 10-19um (oval shaped)
  • 8-10um (on mAFB stains)
A
  • cryptosporidiosis
    • ART + supportive
  • microsporidiosis (Enterocytozoon bieneusi, Encephalitozoon spp)
    • albendazole (except bieneusi) + ART
  • cystoisospora belli (prev isospora)
    • bactrim DS BID x10 days, then secondary ppx
  • cyclospora cayetanensis
    • Bactrim DS BID x14 days, then secondary ppx
95
Q

Classic CMV chorioretinitis findings

A

“scrambled eggs and ketchup” = fluffy, yellow-white retinal lesions w/ perivascular exudate and hemorrhages

96
Q

acute retinal necrosis + rapidly progressive vision loss

A

HSV, VZV, also CMV

97
Q

3 ocular complications of VZV

A
  1. herpes zoster ophthalmicus
  2. acute retinal necrosis
    1. necrotizing retinopathy - anterior uveitis, retinal vasculitis, optic disc papillitis
  3. progressive outer retinal necrosis
    1. retina w/ rapidly coalescing multifocal necrotic lesions (minimal vitritis or vasculitis)
98
Q

pure RBC aplasia w/ severe anemia and paradoxically low retic count

99
Q

helpful tests to differentiate CNS lymphoma from other etiologies (such as toxo)

A
  • CSF EBV DNA
  • SPECT imaging
  • still may require brain bx

Will often still be started on empiric toxo tx while toxo serologies pending, as it is the primary ddx

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