HIV & Antiretrovirals Flashcards
Abacavir
ABC
NRTI
Ziagen
Didanosine
ddI
NRTI
Videx EC
Emtricitabine
FTC
NRTI
Emtriva
Lamivudine
3TC
NRTI
Epivir
stavudine
d4t
NRTI
Zerit
tenofovir
TDF
NRTI
Viread
zidovudine
ZDV or AZT
NRTI
Retrovir
Delaviridine
DLV
NNRTI
Rescriptor
Efaviranz
EFV
NNRTI
Sustiva
Atripla
Nevirapine
NVP
NNRTI
Viramune
Rilpivirine
RPV
NNRTI
Endurant
Complera
Atazanavir
ATV/r or ATV
PI
Reyataz
Darunavir
DRV/r
PI
prezista
fosamprenavir
FPV/r or FPV
PI
Lexiva
indinavir
IDV/r or IDV
PI
crixivan
Lopinavir
LPV/r
PI
Kaletra
Neflinavir
NFV
PI
viracept
Ritonavir
RTV or /r
PI
norvir
Saquinavir
SQV/r
PI
Invirase
Tipranavir
TPV
PI
Aptivus
enfuvirtide
T20
fusion inhibitor
maraviroc
MVC
CCR5 antagonist
raltegravir
RAL
Integrase inhibitor
Elvitegravir
EVG
integrase inhibitor
what is aa normal CD4 count?
500-1000 cell/mm3 or greater
what is the cutoff point CD4 count for AIDS?
<200 cell/mm3
what does having a low cd4 count pts at risk for?
opportunistic infections
malignancies
non-aids related complications
what does the viral load measure?
HIV-1 RNA levels in he blood .
Helps you track the effeicacy of ART
which conditions are considered AIDS defining conditions?
Bacteria -histoplamsosis -MAC -TB -PJP -salmonelace spticemia recurrent -toxoplasmosis Fungus -recurrent vagina candidasis or candidtiasis of lungs, trachea, esophagus but not oral Virus -CMV -HSV Malignacies: kaposi's sarcoma, etc Other: -cryptosporidiosis -encephalopathy -HIV wasting syndrome
who should be routinely tested for HIV according to the CDC?
All americans 13-64 years old -new TB infections -STD treatemt -pregnant women high risk people : MSM , IVDU
what are some of the Non-AIDS releated complications of HIV?
CV disease appearing more frequent and at an earlier age
Renal disease
Liver disease progression (leading cause)
cognitive impairment (dementia)
what may be contributing to the increase in the mortality of HIV patients?
there is always T cell activation and inflammation. Long term inflamation may be the cause of inc mortality
what are the top 5 signs and simptoms of an acute HIV infection?
2-8 weeks after exposure the patient has flu-like symptoms that resolve
- Fever
- Lymphadenopathy
- Pharyngitis
- Rash
- Myalgia/arthralgia
how long does it take for an HIV person to have seroconversion?
4-8 weeks after exposure
which 5 different test are there to test for HIV?
- Rapid HIV test
- ELISA (screening test)
- Western Blot
- OTC HIV test (Ora Quick)
- Viral load assay
Which of the tests serves as the confirmatory test for HIV (the final positive diagnosis)?
Western blot, all positive tests from other tests must be confirmed by this method
how fast is the rapid HIV test?
resuls take less than 60 minutes
how fast is the ELISA?
results in 1-2 days
How fast do you get results with the western blot?
2-3 weeks, sometimes longer
how quick is the OraQuick at geting reuslts?
20-40 mintues
how accurate is the OraQuick ?
92% of time catches the HIV+ patients
99% of the time catches the HIV negative patients
what are risk factors for gettign HIV?
- Blood transfusiton before 1985 fro HIV1, before 1992 for HIV 2
- needle sharing IVDU
- anal > vaginal sexual episode
- perinatal transmission through breastfeeding > 50% risk
- needle stick
Has ART been shown to decrease transmission of HIV?
Yes in serodiscordant couples, who started immediate ART , a study showed that there was 97% HIV transmission reduction (HPTN 052 study)
Which medicaitons was approved in July 2012 to reduce HIV transmission? what is this therapy called?
Tenofovir/emtricitibine (Truvada) for HIV negative individuals (discordant couples / MSM) before sexual couples with HIV + partner. It hisis called PrEP (Pre-exposure prophylaxis)
By how much is PrEP supposed to stop HIV Transmission?
Maximum 73% HIV transmission if > 90%. Drops with decreased adherence
who is eligible for PrEP according to the CDC?
- High risk of acquirng HIV
- documented HIV/HBV negative
- Confirmed CrCL >60ml/min (TDF)
- StD and HCV screened and treat
- avoid PrEP in breast feeding women
dosing for PrEP
Truvada one tablet daily max 90 days supply
must give risk reduction, adherence counseling/condoms
what should you monitor in PrEP patients?
HIV ab and preg test q 2-3 motnhs and when PrEP stopped.
Scr and bone loss
-adherence and HIV risk
what are the toxicities of truvada long term?
renal toxicity
bone demineralization
uknone about risk to fetus/ hiv negative people long term
who should get Post-exposure prophylaxis? PEP
- After a needle stick
- mucocutaneous or cutaneous exposure to blood or body fluids
- after risky sex
- IVDU
- sexual assault
which fluids can transmit HIV and which cant?
YES: blood, semen, vaginal fluids , breast milk
NO: saliva, vomit, urine, feces , sweat , tears, respiratory secretions
how soon should you take the PEP?
ASAP , accoding to CDC 72 hour wind based on animal data, NY up to 36 hours based on amimal data
Dose of PEP agents and duration?
Truvada 1 po daily x 28 days or combivir po bid x 28 days
PLUS
Raltegravir 400mg po bid or poretease inhibitors
Avoid NNRTIs
what clinical marker do you follow for HIV therapy?
HIV-RNA level (viral load), want it to drop as quick as possible within first 4-6 weeks
goals of HIV therapy? why start treatment?
improve QOL reduce mortality and morbidity reduce progression to AIDS decrease inflammation and its complications decrease transmission of HIV
when should you obtain genotype testing for HIV + patients?
at the time of diagnosis
before starting ART
if pregnant
what baseline tests should you order before starting ART?
CD$ cell count Viral load HLA-B5701 allele (if abacavir) CBC w/ differential LFTs FBG SCr, BUN, UA fasting lipids Hep A, B, C serology assess adherence!! mediations history comorbidities
what is the typical skeleton of HAART?
2 NRTIs + [NNRTI or PI or INSTI]
Efavirenz dose for preferred regimen and MOA
NNRTI
60mg po daily
Truvada
tenofovir 300 / emtricitabine 200
truvada dose for preferred regimen
1 tab po daily
when should you avoid truvada?
CrCL < 30 ml/min
Atazanavir dose for preferred regimen?
atazanavir 300mg +RTV 100mg po daily
darunavir dose for preferred regimen?
darunavir 800mg + RTV 100mg po daily
raltegravir preferred regimen dose?
raltegravir 400mg po bid
Preferred regimens to intial treatment
Truvada + efavirenz
Truvada + Atazanavir/r
Truvada + Darunavir/r
Truvada + Raltegravir
when should you avoid efavirenz?
avoid in 1st trimester of pregnancy or women wit hsignificant pregnancy potential
Atripla
TDF+FTC+EFV
Tenofovir + emtricitabine + efavirenz
which of the agents in the preferred regimen are dosed daily vs BID
raltegravir is the only BID dosing, all other agents are once daily
Alternative treatment regimen for initial treatment
Epzicom or Truvada once daily PLUS
- rilpivirine or efavirenz
- atazanavir/r, darunavir/r, FosAPV/r , or Lopinavir/r
- raltegravir or elvitegravir/cobicistat (added with TRUVDA= Strilbild)
- marafirgoc
which medication is interchangeable in HIV regimens with emtricitiabine?
Lamivudine
dose of rilpivirine in alternative regimen
25mg po daily
dose of fosamprenavir in alternative regimen?
FOS 1400mg +RTV 100 or 200mg po daily
FOF 700 bid + RTV 100 po bid
lopinavir dosing for alternative regiment
200mg/ RTV 50mg: 4 tablets daily or 2 tablets bid
dose of maraviroc in alternative regimen?
150- 300mg po bid
How many drugs must you have minumum for a good HIV regimen?
3 at least
which are the only 3 NRTIs that can be used all together in a regimen?
abacavir/lamivudine/zidovudine
maybe tenofovir/lamivudine/zidovudine
Which two-drug combinations should never bus used together?
IDV + ATV
D4T +AZT
FTC+ 3 TC
2 NNRTIs
which always requred ritonavir?
DRV
TPV
SQV
Complera
TDV+FTC+RPV
tenofovir+emtricitabine+rilpivirine
Epzicom
ABC+3TC
abacavir + lamivudine
stribild
elvitegravir/cobicistatin + TDF +FTC
Kaletra
lopinavir/r
lamivudine dosing
300mg po qd
or 150mg po bid
abacavir dosing
600mg po qd or 300mg po bid
tenofovir dosing?
300mg po qd
emtricitabine dosing?
200mg po qd
which of the NRTIs must be taken on an empty stomach?
Didanosine is the only one, the rest are with or without food
combivir dosing
AZT 300mg/ 3TC 150mg 1 po bid
Trizivir dosing
Azt 300/3tc 150/ABC 300 1 po bid
epzicom dosing
ABC 600/ 3tc 300 1 po qd
Atripla dosing
TDF 300/ FTC 200/EFV 600 1 po daily empty stomach
which of the NRTI does not require dosage adjustment in renal insufficiency?
Abacavir, the rest require dosage adjustment or CI if ClCr < 50ml/min
which are the three NRTIs that have anti Hep B activity?
3tc
FTC
TDF
do any of the NRTIs have p450 interactions ?
None!! but other DDIs
what are the calls NRTIs side effects?
N/V/D HA
Delayed AE: mitochondrial toxicity
Black box warning Lactic acidosis and hepatic steatosis
Aside from the typical class effects, what three conditions can occur in patients taking Tenofovir?
BBW if you D/C TDF, can get HBV flare
Fanconi’s syndrome (<2%)
Bone loss/osteoporosis
what is Fanconi’s syndrome? effects?
reabsorption failure in the proximal tubule
inc SCr and BUN, dec K and PO4, glycosuria, metabolic acidosis
who is a tr irks for developing fanconi’s syndrome?
renal disease dehydration DM HTN nephrotoxins low CD4 count older
when should you stop TDF for fanconi’s syndrome? patient educaition?
if proteins > 500mg/24 hours
or increase in BUN/Scr
educated patient on hydration and avoiding nephrotoxins
reversible effect if stopping TDF
what drug should always be ritonavir boosted when used with TDF?
Atazanavir
at what level should you dose adjust tenofovir?
ClCr <50
at what CLCr should you avoid Truvada?
< 30ml/min
viread
tenofovir
Mutation M148V and lamivudine
study by manufacture where there was reduced viral fitness when this mutaiton appeared. Mutation made it resistant to lamivudine but the viral load rebounded to a lower level than expected. Lamivudine may still have partial effect even with this mutation.
lamivudine dosing for HBV/
100mg po daily
at what renal function to adjust lamivudine dosing?
cl cr < 50ml/min
AE of 3tC
well tolerated, minimal toxicity rarely rash pancreatitis in children BBW : lactic acidosi, hepatic steatosis HBV flare if d/c 3tc
Emtriva
Emtricitabine
difference betewen embticitabine and lamivudine?
emtricitabine is flouorinated, hence FTC vs 3TC
AE of FTC
Well tolerated
rash and skin discoloration in palms and soles
BBW lactic acidosis
risk of HBV flare after d/c
when to renally adjust 3 tc?
clcr <50ml/min
FTC dosing
200mg po daily
when does abacavir have an inferior virologic responsce compared to truvada?
when viral load is > 100K
renal adjustment for abacavir?
none
ABC dosing
600mg po qd o r 300mg po bid
AE of ABC?
BBW of ABC hypersensitivity reaction (HLAB5701 testing )
lactic acidosis and hepatic steatosis
associated w possible inc in CV events and MI (?)
ABC and MI risk , what to do?
be cautious/ avoid if strong CV risk factors (alternatives)
lifestyle modification to dec CV risk factors
Switch to another NRTI if feasible but avoid d4t
Don’t stop ART
what is the clinical presentaiton of hypersensitivity to ABC?
Maculopapular or urticarial rash and greater or = 2 of : -Fever -GI (N/V) -lethargy, myalgia, flu-like Sx -pharyngitis
what to do if Hypersensitive to ABC?
STOP
nevery rechallage because can be fatal
when to screen for HLA B5701?
before using abacavir
recording positivity as allergy
what arethe 5 non-nucleoside reverse transcriptase inhibitors?
nevirapine NVP Delaviridine DLV Efavirenz EFV Etravirine ETR Rilpivirin RPV
Etravirine
ETR
NNRTI
Intelence
efavirenz dosing
600mg po daily avoid high fat meal
atripla, one po dialy empty stomach
Rilpivirine dosing
25mg po daily with high fat meal (> 400kCal)
Efavirenz advantages
(+) less dyslipdemia vs PI preserve PI's 1 po daily in atripla no food reqmts no renal dosing long t1/2 life to forgive missed pills
EFV disadvantages
(-) K103N mutaiton confers ressint and X resistance to nevirapine
3A4 inhibtor and inducer
rash
hepatotoxicy/CNT toxicity (dreams, depression)
Preg D
llong t1/2 inc tox and resistance potential
can inc LFTs
what kind of rash wit EFV? what to do if rash
Onset in first few weeks, can be sever to SJ
Can treat through rash with antihistamines if not SJ, if SJ D/C
patient counseling EFV
cha have changes in dreams take PM
take on an empty stomach
avoid alcohol
can you use rilpiverine if K103 mutaiton?
yes!
Radvantages rilpivrine
can treat inf K103 N mutated long 1/2 allows once daily dosing take with food as effective as efavirenz do dc vl Same side effects as EFB but less -inc
contrainidcations with RPV?
PPI’s (Acid labile)
St john’s wart (CYP substrate), Anticonfulstants
Antimycopacterials: rif-
more than one dose of dexamethasone
renal adjustment for complera
avoid if ClCr < 50
dose of atazanavir boosted and unboosted
400mg po qd
or 300mg / R 100mg
fosamprenavir boosted unboosted dose?
1400mg po bid
700mg po bid /100 RTV po bid
Tipranaivir boosted dose ?
no unboosted dose
500mg po bid / RTV 200mg po bidf
Darunavir boosted dose?
600mg /100mg RTV 100mg po BID
800mg /100mg po QD
of ATV, FOS, TPV, DRV, which should be taken w/ or without food?
ATV, TPV, DRV with food
F-APV either or
what are the class Side effects of protease inhibitors?
fat accumulation dyslpidemia insulin resistnace MI risk hepatitis CYP 3A4 inhibition strong esp w/ ritonavir
advantages of protease inhibitors
potent vs other regimens no dosing adjustment in renal dysfunction high resistnace bairer less rash and hepatic toxicity better inc in CD4 vs NNRTIs
which of the PI’s are P450 inducers?
ritonavir (dual), NFV, APV, f-APV, LPV/r
disadvantages of Protease inhibitors
higher risk of GI side effects risk of sulfa corss reactivity ,: fosAPV, TPV, DRV Class tosixicities CYP3A4 interactions higher pill bureden
what are the advantages of using ritonavir for boosting?
increase drug bioavailability
decrease resistnace
lower doses of PI
overcome food restrictions or DDI’s
normal dosage range for ritonavir
100-200mg po once or twice daily
patient ed for ritonaivr
check with doctor before starting any new meds
referigeriate caps (room tecmp 30 days) but not tablet or liquid
tablet is not bioequivaltent with capsules
oral solution cotains 43% alcohol
no renal adjustment
Atazanavir advantages
decrease lipid abnormaliities if unboosted
once daily dosing
lowest pill burden
adverse evetns of ATV?
NVD Rash (can treat through if not too uncomfortable) Jaundice due to inc bilirubin kidney stone (precipitates) delayed PI class toxicity P450 inhibitor
counseling ofr atazanavir
can cause yellowing of skin and eyes. if bothersome, can change. Cosmetic only
Dizzness, abd pain or rash, contact doctor ASAP
Take with food at tsame time as RTV
stay hydrated
if starting new meds inc OTC antacids, tell clinician
darunavir adverse evets
NVD abd pain
URI
Rash Pi calls toxicity and hepatottoxicity
what must you always dispense with darunaivr?
ritonavir at the same time
which PI is inital tx for preganncey?
Lopinavir/r
AE of Lopinavir
NVD especially if QD
HLD, esp TG
Class Tox
PR prolongation
AE of fosamprenavir
NVD Rash nephorlithiasis (kidney stones) class delayed toxicity DDIS
integrase inhibitors
raltegravir
elvitegravir
disadvvantages with raltegravir inc adverse effects
-low geneticbarrier to recisitance
-comparable to evafirenz in trx naive patients
once daily dosing inferior to BID dosing and not recommnended
