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213 Cards in this Set
- Front
- Back
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What are the preferred treatment regimens?
|
1. Atripla (evafivenz, tenofovir, emtricitabine)
2. Atzanavir/rit, truvada (tenofovir, emtricitabine) 3. darunavir/rit, truvada 4. raltegravir, truvada |
|
|
What are the alternative regimens?
|
1. efavirenz, abacavir/lamivuding (Epzicom)
2. rilpivirine, Epzicom 3. rilpivirine/tenofovir/emtricit (Complera) 4. fosamprenavir/rit, epzicom or truvada 5. lopinavir/rit, epzicom or truvada 6. raltegravir, epzicom |
|
|
What is the major US group?
|
M
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HIV groups can affect
|
disease progression, transmission, treatment implications
|
|
|
how many virions can be produced/day?
|
10^9
|
|
|
what the half life of cell free virus in plasma?
|
1.6 days
|
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what is the time from release of new virion to infection of new cell and release of another new virion?
|
2.6 days
|
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What is the best predictor of rate of progression of HIV?
|
Viral RNA
|
|
|
When does acute retroviral syndrome start and how long does it last?
|
2-4 wks after HIV infection and 2-3 wks (prior to seroconversion)
|
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What are the ARS symptoms?
|
fever, lymphadenopathy, rash, myalgia/arthralgia, HA, diarrhea, oral ulcers, leucopenia/thrombocytopenia, mild to mod transaminase elevations
|
|
|
What other conditions look like ARS?
|
EBV and non EBV mono, primary herpes, flu, viral hepatitis, strep infection, secondary syphyllis, drug interactions (rare)
|
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What is the antigen that appears before the AB?
|
P24
|
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What reversal occurs weeks after infection?
|
CD4:CD8`
|
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How do you manage ARS?
|
1. CD4 count 4-6m after seroconversion
2. viral load monitoring for potential set pt 3. Possible tx for 3-4m after infection, risk vs benefit 4. resistance testing |
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|
What are the 4 steps in the HIV lifecycle?
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1. entry (binding, fusion)
2. replication 3. integration 4. protein cleavage |
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What is the most common clade in the US?
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B
|
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What are the possible clades?
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A-K, CRFs
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ART should be initiated, regardless of CD4 count, in pts with:
|
HIVAN, HBV when tx of HBV is indicated, pregnancy
|
|
|
abacavir
|
ziagen
NRTI 1 BID or 2 QD |
|
|
trizivir
|
abacavir/zidovudine/lamivudine
1 BID |
|
|
epzicom
|
abacavir/lamivudine
1 QD |
|
|
didanosine
|
Videx EC
NRTI 1 QD 1/2hr before or 2 hrs after meal |
|
|
emtricitabine
|
Emtriva
NRTI 1 QD |
|
|
atripla
|
emtricitabine/efavirenz/tenofovir
1 HS |
|
|
truvada
|
tenofovir/emtricitabine
|
|
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lamivudine
|
Epivir
NRTI 1 BID or 1 QD |
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Combivir
|
lamibudine, zidovudine
1 BID |
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|
stavudine
|
Zerit
NRTI 1 BID |
|
|
tenofovir
|
Viread
NRTI 1 QD |
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|
Zidovudine
|
retrovir
NRTI 1 BID or 2 TID |
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|
delavirdine
|
rescriptor
NNRTI 2 TID |
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|
efavirenz
|
sustiva
NNRTI 1 HS |
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|
etravirine
|
Intelence
NNRTI 1 BID following meal |
|
|
nevirapine
|
Viramune
NNRTI lead in schedule, 1 QD x 14d, then 1 BID or 1 QD (XR), repeat lead in if d/c >7d |
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|
Rilpivirine
|
Edurant
NNRTI 1 QD |
|
|
Complera
|
rilpivirine/tenofovir/emtricitabine
1 QD with meal |
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|
atazanavir
|
Reyataz
PI 1-2 QD with food + RTV 1 QD |
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Darunavir
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Prezista
PI 2 QD or 1 BID + RTV 1 QD take with food |
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|
Fosamprenavir
|
Lexiva
PI 2 BID or 2 QD+RTV 1-2 QD or 1 BID+RTV 1 BID |
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Indinavir
|
Crixivan
PI 2 TID 1 hr before or 2 hrs after meal OR 2 BID + RTV 1-2 BID without regards to meals Boosted BID dosing--increased nephrolithiasis |
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|
Kaletra
|
lopinavir/ritonavir
PI 2 BID or 4 QD |
|
|
Nelfinavir
|
Viracept
PI 2 BID or 3 TID with food diarrhea Cannot be boosted, inferior potency |
|
|
Ritonavir
|
Norvir
PI 1-4 QD or BID with food |
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Saquinavir
|
Invirase
PI 2 BID + RTV 1 BID with meal or within 2 hrs after meal |
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|
Tipranavir
|
Aptivus
PI 2 BID + RTV 2 BID BBW: intracranial hemorrhages, inferior virologic efficacy, induction properties |
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Raltegravir
|
Isentress
Integrade inhibitor 1 BID |
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|
Enfurvirtide
|
Fuzeon
Fusion Inhibitor SQ BID |
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|
Maraviroc
|
Selzentry
CCR5 antagonist 1-2 BID |
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|
DO not use list
|
1. mono, dual, or triple NRTI
2. efavirenz in pregnancy 3. nevirapine at CD4 greater than cut off 4. etravirine with unboosted PIs or boosted atazanavir, fosamprenavir, tipranavir 5. unboosted darunavir, saquinavir, fosamprenavir, tipranavir 6. 2NNRTIs, reduced levels and inc toxicity |
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|
Do not use: additive hyperbilirubinemia
|
atazanavir + indinavir
|
|
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DO not use; cross resistance
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emtricitabine + lamivudine
|
|
|
Do not use: toxicity
|
didanosine + stavudine
|
|
|
Do not use: antagonistic
|
stavudine + zidovudine
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|
|
Labs at starting ART
|
Cd4, viral load, resistance, HLAB 5701, HBV, basic chemistry, ALT/AST/t bilirubin, CBC w/differential, fasting lipid, fasting glucose, urinalysis, pregnancy
|
|
|
labs after ART or modification
|
2-8 wks
viral load, basic chem, ALT/AST/t bilirubin, CBC w/differential (Zidovudine), fasting lipid |
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On ART: cd4
|
every 3-6m or 6-12m if clinically stable
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On ART: viral load
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every 3-6m
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On ART: basic chem, AST/ALT/t biliribun, CBC w/diff
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every 3-6m
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on ART: fasting lipid
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every 6m if abn at last msmt, then every 12m
|
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on ART: fasting glucose
|
every 3-6m if abn at last msmt, then every 6m
|
|
|
On ART: urinalysis
|
every 12m, if on tenofovir or risk of renal fx, every 6m
|
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PCP prophylaxis: when
|
Primary <200 cells, <14% cd4. d/c when >200 cells/>14% x 3m
Secondary: lifelong or >101 cells with undetect VL |
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PCP prophylaxis: drugs and first line dosing
|
1st line: Bactrim 1 DS PO QD or 1 SS QD. Others: dapsone, dapsone + pyrimethamine + leucovorin, pentamidine, atovaquone, atova + pyrimeth + leucovorin
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Toxoplasma gondii prophylaxis: when
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CD4 <100 and IgG +
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Toxoplasma gondii prophylaxis:drugs and first line dosing
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Bactrim DS QD. others: dapsone, pyrimethamine, leucovorin, atovaquone
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MAC prophylaxis: when
|
cd4 <50,
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|
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MAC prophylaxis: drugs and first line dosing
|
azithromycin 1200mg weekly or clarithromycin 500mg BID or azithromycin 600mg PO twice weekly. others: rifabutin
|
|
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histoplasma capsulatum prophylaxis: when
|
cd4 </= 150, high risk due to occupation, hyperendemic rates
|
|
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histoplasma capsulatum prophylaxis: drugs and first line dosing
|
itraconazole 200mg QD
|
|
|
coccidioidomycosis prophylaxis: when
|
CD4 <250, positive IgM or IgG in pt from disease-endemic area
|
|
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coccidioidomycosis secondary prophylaxis: drugs and first line dosing
|
flucanazole 400mg PO QD or itraconazole 200mg PO BID
|
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when can you d/c primary toxo prophylaxis?
|
cd4 >200 >3m
|
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how long do you treat MAC and when can you d/c, when do you restart?
|
tx 12m, d/c if Cd4 >100, restart if cd4 <100
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|
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what is the prophylaxis for crytococcal meningitis?
|
no primary, secondary until cd4 >=200 cells for >6m on ART. fluconazole 200mg QD
|
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Treatment for PCP: mod to severe
|
bactrim 15-20 TMP, 75-100 SMX/kg/day IV Q6 or Q8 x 21d. Alt: pentamidine 4mg/kg IV QD over >=60min, primaquine 15-30mg QD+clindamycin 600-900mg IV q6 to q8 or 300-450mg PO q6 to q8
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Treatment for PCP: mild to mod
|
bactrim DS 2 tabs TID. Alt: dapsone 100mg QD and TMP 15mg/kg/day PO (3 div d) OR primaquine 15-30 PO QD+clindamycin 300-450 PO Q6 to Q8 OR atovaqone 750mg PO BID with food
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secondary prophylaxis for PCP
|
same as primary
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treatment of toxo
|
pyrimethamine 200mg PO QD, then 50-75mg QD + sulfadiazine 1000mg to 1500mg PO Q6 + leucovorin 10-25mg QD x 6 wks
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|
|
secondary prophylaxis of toxo
|
pyrimethamine 25-50mg PO QD + sulfadiazine 2000-40000 PO QD (2-4 div d)+ leucovorin 10-25mg PO QD (d/c when >200 x 3m)
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treatment of cryptosporidiosis
|
ART, tx diarrea, rehydration
|
|
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microsporidiosis
|
initiate or optimize ART. GI, Enterocytozoon bienuesi (fumagillin 20mg PO TID), others (except eye): albendazole 400mg PO BID (cd4 >200 x >6m), ocular: topical fumagillin eye drops, indefinately
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|
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tx of tuberculosis
|
isoniazid + rifampin/rifabutin + pyrazinamide + ethambutol x 6m or longer
|
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tx of MAC
|
clarithromycin 500mg PO BID + ethambutol 15mg/kg PO QD, rifabutin 300mg PO QD optional
|
|
|
Tx of coccidioidomyocosis
|
mild: fluconazole 400mg PO QD or itraconazole 200mg PO TID x 3d, then 200mg BID
Severe, nonmeningeal: ampho B deoxy 0.7-1mg/kg IV QD OR ampho lipid 4-6mg/kg IV QD, until clinical improvement then switch to azole meningeal: fluconazole 400-800mg PO or IV QD |
|
|
secondary prophylaxis of coccidio
|
fluconazole 400mg PO QD or itraconazole 200mg PO BID
|
|
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tx of cytomegalovirsu
|
ganciclovir intraocular implant + valganciclovir 900mg PO BID x 14-21d then QD
Give one dose of intravitreal ganciclovir until implant placed small peripheral lesions: valganciclovir 900mg PO BID x 14-21d, then 900mg PO QD |
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|
secondary prophylaxis of CMV`
|
valganciclovir 900mg PO QD or ganciclovir implant (replace every 6-8m if CD4 <100)+valganciclovir 900mg PO QD
|
|
|
other tx options for CMV
|
cidofovir (doesn't require phospohyrlation, 2 wks infusions)
foscarnet (increased resistance over time) |
|
|
tx of latent infection TB, isoniazid dosing. What is pyridoxine for?
|
daily or twice weeklly x 9m
neurological toxicity |
|
|
Tx of active TB
|
isoniazide, rifampin or rifabutin, pyrazinamide, etheambutol x 2m OR isoniazid & rifambin/rifabutin x 4m
Daily then 3x/wk (2xwk if cd4>100) |
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|
treatment duration of TB
|
cavitary 9m
extrapulm 9m CNS/bone/joint 12m |
|
|
what TB drug should you avoid with PIs?
|
rifampin
|
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What are the OI that most ofren result in IRIS?`
|
TB/MAC
|
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Who usually gets IRIS?
|
high VL and very low cd4 prior to ART (<50)
|
|
|
How to tx IRIS?
|
Prenisone 20-40mg PO QD (MAC 4-8wks)
|
|
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When can you d/c prophyl of PCP?
|
VL undetectable, CD4>200 x 3m on ART, restart when <200 or reinfection
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When would you prophyl PCP for life?
|
when infection occurs at cd4>200
|
|
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when to give steroids in PCP?
|
within 72 hrs of tx, prednisone 40mg BID x 5d, 40mg QDx5d, 20mg QD x 11d
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What cd4 does cryptococcal meningitis & toxo usually occur?
|
<100 but mostly <50
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primary prophyl of cyrptococcal meningitis?
|
none
|
|
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when to restart primary prophyl of toxo?
|
cd4<100-200
|
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|
duration of tx for toxo
|
6wks
|
|
|
when to use steroid in tx of toxo?
|
tx mass effect associated with focal lesions or associated edema, dexamethasone 4mg IV Q6, 1-3mg PO TID
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when to d/c secondary prophy of toxo?
|
no s/sx, cd4 >200 x6m, reinitiate when cd4 <200
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what is the leucovorin for?
|
decrese bone marrow suppression due to pyrimethamine (folic acid)
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who gets MAC?
|
cd4<50
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when to d/c primary proph of MAC?
|
CD4>100 x >3m, restart when CD4 <50
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virologic failure
|
inability to achieve or maintain suppression of viral replication (<200 copies)
|
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incomplete virologic failure
|
2 consecutive plasma HIV RNAs >200 after 24 wks tx
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persistent low level viremia
|
confirmed detectable RNA <1000
|
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virologic rebound
|
confirmed detectable RNA >200 after virologic suppression
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immunologic failure
|
failure to achieve and maintain adaquate cd4 response despite virologic suppression (>50-150 cells/yr), cd4 plateaus at 4-6 yrs
|
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benefits of genotype
|
less expensive, quicker, historical record, more data from trials
|
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challenges of genotype
|
interpretation, misses 10% of minority subtypes, only assess known mutations, combo mutations may have diff effect, difficult to interpret with mutiple mutations
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benefits of phenotype
|
drug susceptibility infered, aggregate of multiple mutations, confort with inhibitory concnetration terms
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limitations of phenotype
|
long time, $$$, biological cut offs are stated without matching drug levels, insensitive to low levels of curculating virus (5-20%)
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wild type virus
|
original parent virus that was predominant prior to use of ARV. in phenotypic testing, is compared to lab reference strain.
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K65R mutation is beneficial, why?
|
incresases susceptibility to zidovudine
|
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L74 increases susceptibility to what?
|
zidovudine, tenofovir
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|
M184V`
|
high resistiance to lamivudine, emtricitabine
low (requries multiple muts K65R & L74V or 3 TAMs to get high level): didanosine, abacavir Slow replication with resistance. |
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|
TAMS: Type 1`
|
T215Y, abacavir, didanosine, tenofovir, stavudine (some zidovudine)
|
|
|
TAMS: Type 2`
|
D67N, K70R, T215F, K219Q/E
zidovudine (some stavudine) |
|
|
Why is type 1 TAM beneficial?
|
increases susceptibilty to NNRTIs
|
|
|
K65R
|
intermediate: tenofovir, abacavir, didanosine, lamivudine/emtric
low: stavudine |
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|
Which mutations have bidirectional antagonistm?
|
K65 & TAMS
|
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|
zidovudine suppresses the emergence of:
|
K65R
|
|
|
L74V
|
intermediate: didanosine, abacavir
|
|
|
what is the benefit of L74V
|
slight increase suscepbiilty of zidovudine, tenofovir
|
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what is the epzicom mutation?
|
L74V/M184V
|
|
|
What is the truvada mutation
|
K65/M184V
|
|
|
Q151M
|
high level: zidovudine, stavudine, didanosine, abacavir
intermediate: tenofovir, lamivudine/emtric |
|
|
NNRTI mutations
|
K103N, Y181, G190, high level to nevirapine, variable to efavirenz (V106A/Y181C 2x, G190 6x, K103N 20x, Y188L/G190 50x)
|
|
|
D30N
|
nelfinavir
|
|
|
I50L
|
atazanavir
|
|
|
I50V
|
fosamprenavir
|
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V82L/T
|
tipranavir
|
|
|
L90M
|
multiple PIs
|
|
|
raltegravir resistance
|
N155, Q148
|
|
|
enfurvirtide resistance
|
gp 41 region
|
|
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What mutation is often found in HIV2 pts
|
Q151M
|
|
|
replication capacity
|
rate the virus can replicate when exposed to ARV as opposed to pt's wild type virus
|
|
|
why does K103N exist for a long time when drugs are removed?
|
because it has primary high level resistance
|
|
|
What drugs are not effective for HIV2?
|
NNRTIs, fusion inhibitor (enfurvirtide)
|
|
|
how high must RNA be to do resistance
|
>500
|
|
|
Which class is most likely to cause rash?
|
NNRTI
|
|
|
All PIs inhibit 3a4 except:
|
tipranavir
|
|
|
ritonavir inhibits:
|
3a4, 2d6
|
|
|
what is the order on NNRTIs likely to cause rash
|
nevirapine>efavarinz ~ etravirine
|
|
|
nevirapine cut offs
|
CD4 >400 men, >250 women
|
|
|
which NNRTI has increased risko f hepatotoxicity?
|
nevirapine
|
|
|
efavirenz with food?
|
no
|
|
|
Which NNRTI can you not use iwth PPIs and must separate from H2 & antacids?
|
rilpivirine
|
|
|
WHen is rilpivirine not as effective?
|
VL >100,000
|
|
|
Rilpivirine pregnancy category
|
B
|
|
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which NNRTI is not first line?
|
etravirine
|
|
|
which NNRTI has lead in dosisng?
|
nevirapine
|
|
|
which NNRTI is proven beneficial in pregnancy?
|
nevirapine
|
|
|
which NNRTI has great risk of hepatoxicity?
|
nevirapine (>women)
|
|
|
rilpivirine: big or small pill?
|
small
|
|
|
PI toxicities:
|
dyslipidemia, insulin resistance (related to ritonavir dose)
|
|
|
Toxicities of Lopinavir/rit & indinavir
|
MI, CAD, Stroke
|
|
|
toxicity of amprenavir/fosampr
|
MI
|
|
|
toxicity of saquinavir/rit
|
PR & QTc prolongation
|
|
|
Which PI requires acid environment?
|
Atazanavir
|
|
|
which PI has no lipid elevations even with ritonavir?
|
atazanavir
|
|
|
Which PI has no cross resistance?
|
atazanavir
|
|
|
which PI causes hyperbilirubinemia?
|
Atazanavir,
|
|
|
which PI (besides saquinavir) has risk of PR prolong?
|
atazanavir
|
|
|
which PI has risk of nephrolithiasis?
|
atazanavir (& indinavir)
|
|
|
which PI does not elevate lipids?
|
atazanavir
|
|
|
which PI has corss resistance with tipranavir?
|
darunavir
|
|
|
What are concerns with Darunavir?
|
lpids, glucose, hepatotox (esp with hep)
|
|
|
totall pills for kaletra?
|
4
|
|
|
what is the first line agent in pregnancy?
|
lopinavir/ritonavir (kaletra)
|
|
|
kaletra food restrictions?
|
no
|
|
|
which PI has low risk of resistance?
|
Kaletra
|
|
|
limitations of kaletra
|
GI (nausea), lipid elevation (TRIG), CV, decreased conc pregnancy
|
|
|
which PI is 3a4 inhibitor & substrate and which is inducer and substrate?
|
inhibitor: darunavir
inducer: fosamp |
|
|
refrigerate ritonavir?
|
capsules-yes (<30d), no to solution
|
|
|
limitations of ritonavir
|
GI, paresthesias, taste, lipids, hepatitis
|
|
|
Why not indinavir?
|
TID, fluid/food restict, boosted BID dosing has increased nephrolithiasis
|
|
|
why not nelfinavir?
|
inferior potency & diarrhea
|
|
|
why not ritonavir (alone)?
|
high pill burden, GI intol, lipids
|
|
|
why not tipranavir?
|
inferior virologic efficacy, BBW--intracranial hemorrhages, induction properties
|
|
|
food with ralgegravir?
|
no restrictions
|
|
|
limiotations with raltegravir?
|
CPK elevations (esp with statins & PIs), ? potency, low genetic barrier to resistance, BID dosing
|
|
|
benefits of raltegravir?
|
fewer DI, no food restrict, UGT1A1 med glucoronidation, well tol, comparative to efavirenz at 96 wks
|
|
|
which NRTI does not have to be adjusted for renal dysfx?
|
abacavir
|
|
|
NRTI class SE?
|
GI (N/V/D), lactic acidosis
|
|
|
What are general statements about NRTIs?
|
lower potency vs PI or NNRTI, all are prodrugs (need phosphorylation), QD except zidovudine and stavudine
|
|
|
which NRTI has a food restriction?
|
didanosine (empty stomach)
|
|
|
which drug causes hyperpigment of soles/palms?
|
emtricitabine
|
|
|
which drug has nephrotoxicity with fanconi syndrome or acute renal failure?
|
tenofovir
|
|
|
why is tenofovir use with caution in pregnancy?
|
bone demineralziation
|
|
|
what is alcohol interaction with abacavir?
|
increases by 41%
|
|
|
which NRTi has increased risk of drug failure with VL>100,000
|
abacavir
|
|
|
what are sx of abacavir hypersens?
|
4-6 wks: fever, skin rash, fatigue, N/V/D, abd pain, SOB, cough, sore throat
|
|
|
abacavir test
|
B*5701
|
|
|
which PI has best CNS penetration?
|
zidovudine
|
|
|
which PI causes macrocytosis?
|
zidovudine
|
|
|
what are limitations of zidovudine?
|
BMS, macrocytosis, neutropenia, GI, HA, fatigue, myopathy, finger nail discolor
|
|
|
which didanosine formulation is preferred?
|
EC (less diarrhea)
|
|
|
What is the major limitation of didanosine?
|
mitochondrial toxicity
|
|
|
what are limitations of didanosine
|
pancreatitis, neuropathy, mito tox, CI with ribavirin
|
|
|
what is the major limitation of stavudine?
|
mitochondrial tox
|
|
|
what are limitations of stavudine?
|
mito tox, peripehral neuropathy, lipoatrophy, lactic acidosis, hepatic steatosis (DEATH)
|
|
|
s/sx of lactic acidosis
|
persistant abd pain, n/v/d, wt loss, weakness, liver enlarge
|
|
|
risk factors for lactic acidosis
|
obese, women w/prolonged use of NRTI
|
|
|
what are the thymidine analogs and what is the problem?
|
zidovudine, stavudine, lipoatrophy
|
|
|
what is the major ADE of tenofovir
|
acute tubular necrosis
|
|
|
cross resistance in enfuvirtide?
|
no
|
|
|
food restrictions with miraviroc?
|
no
|
|
|
maraviroc DI?
|
3a4 substrate
|
