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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
Preferred NRTI skeleton with pregnant
* ABC/3TC, tenofovir/FTC or 3TC * Alt: zidovuine/3TC _NOT rec_: 3 NRTIs, didanosine, stavudine
26
What to give in pregnancy if near delivery and when?
IV zidovudine if RNA \>1000 or unknown rec c/s @ 38wks
27
Which ART also has HBV activity?
* lamivudine * FTC * tenofovir need 2 rx when tx HBV (3 for HIV) =tenofovir + [3TC or FTC] + 3rd rx
28
TB-HIV Important rx to ensure is used:
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)
29
if ART started prior to genotype, what should you use?
BIC, DOR/c, or DTG + TAF/FTC
30
Chronic/Longer Term SEs w/ ART * CVD * kidney stones * metabolic (glucose, lactate, lipids) * morphologic (lipoatrophy, lipohypertrophy) * peripheral neuropathy * proximal RTA (Fanconi) * wt gain
* ?ABC, PIs (exc atazanavir) * indinavir \> atazanavir * older PIs (stavudine, esp) * LA - stavudine, zidovudine; LH - older PIs * stavudine, didanosine * TDF * BIC, DTG
31
Acute/Early SEs w/ ART: * GI * anemia, neutropenia * BMD * CNS * fatigue * indirect hyperbili * rash
* zidovudine, didanosine, TDF, PIs (?all ART) * zidovudine * TDF * efavirenz * zidovuine * atazanavir, indinavir * NNRTIs
32
ART s/e SJS
nevirapine, etravirine (NNRTIs) also darunavir (PI)
33
ART s/e pancreatitis
older nucleoside analogs: didanosine, stavudine
34
ART s/e lactic acidosis
older nucleoside analogs: didanosine, stavudine
35
ART s/e hepatitis
think NNRTIs, PIs ## Footnote \*nevirapine - F w/ CD4\>250; M w/ CD4\>500
36
Cytochrome P450 3A4 inhibitors (classes)
PIs (ritonavir = most potent; also cobi) \*increases level of other metabolized rx Concern w/: rifampin, rifabutin, azoles, antiseizures, statins, midazolam, HCV rx
37
Cytochrome P450 3A4 inducers
NNRTIs (EFV, ETR, NVP, RPV. **Not DOR**) ## Footnote \*\*decrease levels of other metabolized drugs Concern w/: rifamycins, azoles, antiseizure rx, statins, HIV PIs, maraviroc)
38
Toxicities and considerations of atazanavir/r or c (PI)
* elevated indirect bilirubin * GI * avoid PPI * kidney stones (uncommon)
39
Toxicities and considerations of darunavir/r or c (PI)
preferred over atazanavir skin rash (rare) EM, SJS, TEN have occurred \*activity vs PI-R strains
40
Toxicities and considerations of rilpivirine (NNRTI)
not well absorbed w/ PPI _**\*\*\*not for RNA \>100k or CD4\<200**_
41
Toxicities and considerations of EFV (NNRTI)
* CNS tox - neuropsych (vivid dreams, hallucinations) * suicidality, depression (don't use if h/o) * rash * suicidality * \*TDF/TFC/EFV (1 pill daily)
42
Toxicities and considerations of doravirine (NNRTI)
* decreased CNS tox c/w EFV * decreased lipid abnormalities \*TDF/FTC/DOR = 1 pill daily
43
Toxicities and considerations of zidovudine (NRTI)
GI, anemia, lipoatrophy
44
Toxicities and considerations of ABC/3TC (NRTI combo)
\*recommended w/ DTG only * hypersensitivity reaction * ??increased risk of MI (w/ ABC)
45
Toxicities and considerations of tenofovir
renal, bone (w/ TDF)
46
What to consider when ABC, TAF/TDF can't be used
* DTG/3TC **(except VL\>500k, HBsAg+)** * DRV/r + RTG **(if RNA \< 100K and CD4\>200)** * DRV/r+3TC
47
circumstances in which you can't start with DTG/3TC
* RNA \> 500k (lamivudine) * HBVsAg+ (only has one active HBV agent) * no resistance results (really only used as switch in well-controlled pt)
48
which ART can you not use with VL\>100k? \>500k?
\>_100k_ = rilpivirine (or ABC) \>_500k_ = lamivudine
49
Detecting HIV Infection
_Screening_: 4th ELISA (Ag/Ab), qual HIV RNA _Supplemental/Confirmation_ = highest specificity; multispot/geenius (confirms HIV-1 or -2)
50
For reference: HIV Detection Timing
51
Other conditions where PJP is common
52
tox of atovaquone
* absorption if low-fat diet * rash * N/V/D * increased LFTs
53
Tox of IV pentamidine
* 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
Tox of TMP/SMX
* decreased WBC and plts * increased LFTs, SCr * "sepsis" * Hyperkalemia (TMP) - pumps out TMP instead of K * cross-reactivity with dapsone!
55
Which tx for PJP can lead to torsades?
pentam
56
Reasons to deteriorate during PJP Tx
* fluid overload: iatrogenic, cardiac, renal failure (sulfa-, pentam-related) * anemia * methemoglobinemia (dapsone, primaquine) * PTX * unrecognized concurrent infection * IRIS
57
Average time to clinical improvement in PJP
4-8 days (rads obviously lags clinical improvement)
58
Therapy for PJP
1. TMP/SMX 2. Alt: parental pentam, atovaquone, clinda/primaquine 3. + ?Adjuvant steroids
59
PJP
60
Dx of PJP PNA
* 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
Very uncommon manifestations of PJP (primarily pulmonary infection)
* ocular * pulmonary blebs, cavitation, PTX * splenic disease * digit necrosis
62
rarely cause pulm dz in HIV (even if isolated from secretions)
CMV MAC HSV
63
Uncommon etiologies of HIV-assoc Pulm d/o (less likely to be answers on boards, but need to consider)
* aspergillus * histo/cocci * staphylococci * toxo * lymphoma * KS
64
Comorb that predispose to pneumococci which are over-represented in HIV
* opioid use d/o, EtOH, tobacco * lack of immunization * COPD, CHF, obesity * MRSA colonization * liver disease
65
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:
* \>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
Common causes of HIV-assoc Pulm d/o
* pneumococcus * hemophilus * PJP * TB * atypicals/viral
67
Secondary OI ppx | (what, when)
* **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
_When/What for Primary Ppx_ * PJP * Toxo * Cocci * MAC
* _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
When to start ART following OIs * list exceptions
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
Clinical Indicators of Immunosuppression
* OP candidiasis * Hairy Leukopenia * Disseminated VZV
71
2 skin conditions often confused with each other
KS Bartonella (bacillary angiomatosis)
72
What two PJP/toxo ppx rxs cross-react (don't use with allergy to one)
Dapsone and sulfonamides | (Pentam doesn't have toxo)
73
N155H Q148H/R/K Y143C
R to RAL, EVG use DTG BID if able
74
R263K
DTG
75
mutation w/ highest level of R to elvitegravir
Q148R
76
I50L
resistance to atazanavir ## Footnote \*\*most pts w/ failure on 2 NRTI + bPI have NO PI mutations \*\*\*requires multiple mutations
77
Rilpivirine failure
a/w E138K, K101E, Y181C --\> ALL NNRTIs lost
78
basic NNRTI R knowledge
* older NNRTIs (efavirenz, nevirapine) = LOW barrier to resistance with complete cross-reactivity * newer NNRTIs (etravirine, rilpivirine, doravirine) - higher barriers to resistance
79
Y181C
nevirapine (NNRTI)
80
K103N
efavirenz and nevirapine (NNRTI) ## Footnote \*\*\*retains susc to etravirine and rilpivirine
81
74V ## Footnote Selected by: Effect:
selected by ABC, ddI * decr susc to ABC, ddI * increased susc to AZT, TDF
82
K65R ## Footnote Selected by: Effect:
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
151M, 69ins ## Footnote Selected by: Effect:
* selected by AZT/ddI, ddI/d4T * resistance to ALL NRTIs * T69ins = TDF R
84
TAMS ## Footnote Selected by: Effect:
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
M184V ## Footnote Selected by: Effect:
selected by 3TC, FTC * loss of susc to 3TC, FTC * dec susc to ABC * delayed TAMS \*\*increased susc to AZT, d4T, tenofovir
86
N155H ## Footnote Q148H/R/K Y143C
RAL, EVG
87
spontaneous PTX or CXR w/ b/l butterfly-pattern GG intersitial infiltrate (classic, but not commonly seen)
think PJP
88
Dx tests for PJP
* 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
Diagnostics for histo
* 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
Advanced HIV person from SE Asia disseminated, multiorgan disease characteristic skin lesions w/ prediliction for liver (marked LFT elevation)
think talaromycosis tx w/ LAMB x2wks, then itra
91
Preferred ART regimen with TB co-infection
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
CD4 \<50 fevers, night sweats, wt loss, chronic D, HSM, diffuse LAD
consider disseminated MAC
93
tx of bacillary angiomatosis (or peliosis hepatitis)
erythromycin or doxycycline x3+ mos
94
diarrheal illness in advanced HIV (and tx) * 4-6um * 1-5 um * 22-23 x 10-19um (oval shaped) * 8-10um (on mAFB stains)
* 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
Classic CMV chorioretinitis findings
"scrambled eggs and ketchup" = fluffy, yellow-white retinal lesions w/ perivascular exudate and hemorrhages
96
acute retinal necrosis + rapidly progressive vision loss
HSV, VZV, also CMV
97
3 ocular complications of VZV
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
pure RBC aplasia w/ severe anemia and paradoxically low retic count
parvo B19
99
helpful tests to differentiate CNS lymphoma from other etiologies (such as toxo)
* CSF EBV DNA * SPECT imaging * still may require brain bx ## Footnote *Will often still be started on empiric toxo tx while toxo serologies pending, as it is the primary ddx*
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