Therapeutics - HIV part 2 Flashcards
name 4 types of entry inhibitors
fusion inhibitor
CCR5 antagonist
post attachment inhibitor
attachment inhibitor
name a fusion inhibitor
enfuviritide
name a CCR5 antagonist
maraviroc
name a post attachment inhibitor
ibalizumab
name an attachment inhibitor
fostemsavir
in general, what is the role in therapy for entry inhibitors
usually reserved for people who are failing the other classes of antiretrovirals, with the exception of maraviroc - may be used besides in failing therapy
***which HIV drug has a need for tropism testing? why? what class is it?
MARAVIROC
it’s a CCR5 antagonist - therefore, it will only work on a CCR5 tropic virus and we need to test for this
true or false
ALL of the entry inhibitors can be taken with or without food
true
true or false
there is no concern with CYP450 interactions with entry inhibitors
FALSE - there is for most of them
fostemsavir + ethinyl estradiol
what class is fostemsavir?
attachment inhibitor
levels of ethinyl estradiol will increase
true or false
several entry inhibitors are given by injection
true
enfuvirtide, ibalizumab
which entry inhibitor has a BBW of hepatotoxicity
maraviroc
name 5 integrase inhibitors
raltegravir
bictegravir
elvitegravir
dolutegravir
cabotegravir
true or false
integrase inhibitors are not used often
FALSE - they are
not a lot of side effects, they work well, and resistance is pretty rare
only integrase inhibitor that MUST be taken with food
(all others are with or without)
elvitegravir
which 2 integrase inhibitors undergo UGTA1A1 glucuronidation
cabotegravir and raltegravir
which integrase inhibitor’s use is restricted only to those whose creatinine clearance is over 70mL/min?
raltegravir
which 2 integrase inhibitors have CYP450 interaction concern?? which additionally has a binding interaction concern?
elvitegravir and dolutegravir
dolutegravir
which integrase inhibitor causes neural tube defects in utero?
dolutegravir
what class is considered last line therapy for HIV
capsid inhibitors - they’re new and not really used yet at all in practice – only for heavily experienced adults with multi-drug resistance HIV infection
name the only capsid inhibitor
lenacapavir
what is lenacapavir contraindicated with?
strong CYP3A4 inducers
it is a moderate CYP3A4 inhibitor
true or false
lenacapavir can be taken with or without food
true
HAART meaning
highly active antiretroviral therapy
true or false
if a patient is antiretroviral naive, they do not have a resistant strain
FALSE - they still can - even if they never took any HIV meds
for example, the virus transmitted to you may have been resistant already
name some baseline labs that may be conducted before antiretroviral therapy is started
scr/cr cl
hepatic function
for abacavir - HLAB701 test
for miraviroc - tropism test for CCR5
name 4 goals for treating HIV
-suppress viral load
-restore immunologic function (increase CD4)
-reduce morbidity/mortality and improve quality of life
-prevent HIV transmission to others
CD4 and viral load test should be conducted at baseline, and how long for routine monitoring?
every 3-6 months
true or false
after initiating ART (antiretroviral therapy), CD4 count should be assessed at 2-8 weeks following initiation of therapy
FALSE
should asses VIRAL LOAD 2-8 weeks after initiating therapy
we do NOT check the CD4 count this soon. viral load is more indicitive of how the patient is responding to therapy
when is HIV treatment started
ASAP and aggressively. there is zero reason to wait
ART is recommended for ALL persons with HIV to reduce morbidity and mortality AND….
to prevent transmitting HIV to others
based on the guidelines, name 3 therapies that are considered 1st line for STARTING PATIENTS on HIV medication who do NOT have a history of using long acting cabotegravir as PREP
-biktarvy: Bictegravir + TAF + Emtricitabine
-Dolutegavir + TAF or TDF + Emtricitabine or Lamuvidine
-DO NOT USE this regimen if patient’s viral load is greater than 500,000, HBV coinfection, or have been started on therapy before the results of the resistance test:
Dolutegravir + Lamuvidine (dovato)
ALL HAVE AN INTEGRASE INHIBITORS!!!! GUIDELINES RECOMMEND THE USE OF AN INTEGRASE INHIBITOR
patient HAS a history of using long acting cabotegravir as PREP, and therapy is being started BEFORE the results of the INSTI genotype resistance testing
what therapy should they be put on?
Darunavir or Darunavir + low dose ritonavir + TAF or TDF + Emtricitabine or Lamuvidine
(pending the results of the genotype test)
physician is concerned about the renal or bone adverse effects associated with TAF/TDF
what therapy is recommended by the guidelines
integrase inhibitor + 2 NRTIs
(ie: dolutegravir + abacavir + lamuvidine)
IF HLA-B*5701 IS NEGATIVE (abacavir concern) also avoid in CV disease bc of abacavir
give 2 general regimens that the guidelines recommend to avoid an integrase inhibitor based regimen
boosted protease inhibitor + 2 NRTIs
NNRTI + 2 NRTIs
name 5 therapies that are NOT recommended as INITIAL antiretroviral treatments by the guidelines
raltegravir-based regimens
elvitegravir/cobicistat-based regimens
booster Atazanavir-based regimens
Efavirenz-based regimens
Rilpivirine + TDF + FTC
2 examples of when we should NOT use rilpivirine as initial therapy
CD4 count less than 200, viral load greater than 100,000 copies
because higher rates of failure
HLAB5701 allele test is positive OR is unknown
what drug should we NOT use
abacavir
viral load is higher than 500,000
what 2 therapies should NOT be used
rilpivirine + TAF + emtricitabine
dolutegravir + lamuvidine
in general, if the patient has chronic kidney disease (CrCl <60mL/min), which drug should definitely be avoided
TDF - TAF has better renal and bone properties
patient has osteoporosis
which particular drug should be avoided
TDF - TAF is better
2 drugs that should be avoided if patient has psychiatric illness
rilpivirine, efavirenz
after the initiation of appropriate antiretroviral therapy, how long should it be until the viral load should become UNDETECTABLE? (<50copies/mL)
How long should it be just to see improvement in the viral load?
12-24 weeks – or within 6 MONTHS
should be around 4 weeks to see improvement in the viral load
1 of the reasons a patient may fail their initial antiretroviral treatment is if their is an alteration in the drugs’ pharmacokinetics
given an example of this
if the patient has bad diarrhea as a side effect of one of the drugs, the drug isn’t being absorbed well and the patient will fail treatment
true or false
therapeutic drug monitoring is not done for HIV drugs
true
define virologic suppression
confirmed viral load levels below LLOD (lower limit of detection) should occur within 24 weeks
explain what virologic failure is
inability to achieve OR MAINTAIN viral load less than 200
sometimes pt is on therapy and doing well, but it goes above 200 again
what is a virologic blip
after suppression, random test comes back as extremely high, even when the patient has been controlled consistently
when you repeat the test, it comes back less than 200
we dont know why this happens
define an incomplete virologic response
2 consecutive viral load levels greater than 200 even after 6 months on therapy
low-level viremia
confirmed detectible viral load less than 200
true or false
drug resistance is not considered cumulative
FALSE - it is
meaning that prior history is very important – all adds up
a patient is on a 3 drug regimen. they develop resistance to 1 or 2 of the drugs
what should be done?
throw the entire regimen away and start over
PREP vs PEP
prep = pre exposure prophylaxis. HIV-negative patient takes combo drug on a daily basis (or cabotegravir XR injectable suspension bimonthly) BEFORE the potential exposure occurs
PEP = post exposure prophylaxis
HIV negative patient takes a full 3-drug HIV regimen for 28 days AFTER the potential exposure occurs
how can PEP be dividied
occupational and non occupational (ie - sexual, IV drug user)
as mentioned, PrEP is when an HIV negative patient takes either combo drug therapy daily, or cabotegravir XR injectable bimonthly BEFORE the potential exposure occurs
name 2 of these possible combination drugs
TDF + emtricitabine
TAF + emtricitabine
PEP should be started within how long after the exposure?
within 72 hours after the exposure
give an example of a PEP regimen
how long is it taken?
for 28 days and started within 72 hours after exposure
dolutegravir + TDF or emtricitabine
according to the CDC, prep is ONLY for……
people who are at ongoing, substantial risk of HIV infection
according to the CDC, PEP should be offered to who
people who present to dr after a single high risk event of potential HIV exposure
true or false
PREP protects against HIV as well as other STI’s
FALSE
ONLY HIV
name the conditions that identify the patient as having a substantial risk of acquiring HIV infection
anal or vaginal sex in the past 6 months and ANY of the following:
-HIV positive partner (esp if unknown or undetectable VL)
-bacterial STI in the past 6 months
-history of inconsistent or no condom use
OR
HIV positive injecting partner OR share injecting equipment
name 4 conditions in which ALL must be met to be considered CLINICALLY eligible to receive PREP
-documented negative HIV test result within 1 week after initially prescribing prep
-no signs or symptoms of acute HIV
-creatinine clearance greater than 30
-no contraindicated meds
what are common signs and symptoms of an acute HIV infection
flu like symptoms
true or false
if a person tests (+) for HIV, they are not a candidate for prep
TRUE
want to give full therapy immediately
name the med/duration for prep treatment
truvada (TDF + Emtricitabine)
less than or equal to a 90 day supply
oral, once daily dosing
OR
for men and trans women at risk for sexual acquisition - daily, continual dosing of descovy (TAF + emtricitabine) up to 90 day supply
NO MORE THAN 3 MONTHS AND NO REFILLS!!!! want to test them and make sure it’s working and they’re not (+)
why is descovy (TAF + emtricitabine) not used in heterosexual women, and only used in men and trans women?
bc not studied in heterosexual women for prep
truvada is used instead
when prep is being administered, what information should be collected every 3, 6, and 12 months?
3 months - HIV test, adherence
6 months - assess renal function if over 50 or have low cr cl at start
12 months - assess renal function of ALL patients. chlamydia screening for hetersexual women and men
if on TAF + emtricitabine, assess weight, triglycerides, cholesterol
what is the only not oral prep
cabotegravir injection
only difference between determining if a patient is eligible for prep between truvada/descovy vs cabotegravir
all same requirements, except for cabotegravir there is no creatinine clearance cut off
dosage cabotegravir for prep
600mg IM 3mL single dose
4 weeks later - 2nd dose
every 8 weeks thereafter they get another dose
differentiate between primary and secondary prophylaxis for opportunistic infections
primary - for patients who have NEVER HAD infection. to prevent the first episode of an opportunistic infection
secondary - prophylaxis for patients who have had previous cases of the opportunistic infection
most common opportunistic infection in HIV patients
candidiasis fungus
oral or esophageal
treatment for oral candidiasis (thrush)
also what is duration
7-14 days
most often - fluconazole 100mg PO QD
ALTS are clotrimazole troche 5x a day, nystatin suspension, posaconazole
treatment for esophageal candidiasis
also what is duration
14-21 days (longer than thrush)
fluconazole 100mg QD or itraconazole solution 200mg QD
alts = viriconazole, isavuconazole, caspfungin
true or false
we normally do not give prophylaxis for thrush
TRUE
only if they have it an absurd amount of times every year (which is rare)
name 4 opportunistic infections in HIV patients
candidiasis
PCP (pneumocystis pneumonia)
toxoplasma gondii
MAC (mycobacterium avium complex)
when is primary prophlyaxis for PCP indicated
HIV + and CD4 count less than 200
primary prophylaxis regimen for PCP
when is the therapy discontinued
bactrim (DS) QD – can be on for years
alts are tmp/smx SS QD, dapsone, atovaquone, pentamide
discontinued when CD4 is greater than 200 for 3 or more months
(can consider if between 100-200 and VL undetectable for 3-6 months tho)
when is secondary prophylaxis indicated for PCP
following a PCP episode
treatment is same as primary prophylaxis. also stopped under same conditions
when is primary prophylaxis for toxoplasma gondii indicated?
what is the treatment?
when can it be stopped?
when CD4 count less than 100 and IgG antibody (+) to toxo
treatment, like PCP, is bactrim DS QD
stopped under same conditions - when CD4 greater than 200 for 3 or more months. (can consider when cd4 100-200 and VL undetectable for 3-6 months)
**patient has CD4 count 80
what opportunistic infections are they at risk for
PCP
toxoplasma gondii
how does a patient with toxoplasma gondii present
stiff neck, altered mental status
when is secondary prophylaxis for toxoplasma gondii indicated?
what is treatment?
when can it be discontinued?
indicated following a toxo episode
treatment is same
can stop when CD4 greater than 200 for 6 or more months and have no signs or symptoms of toxo infection
when is primary prophylaxis for MAC (mycobacterium avium complex) indicated?
NOT recommended for adults/adolescents who immediately initiate antiretroviral therapy
however, IS indicated if:
-HIV (+)
-not on fully suppressive therapy (this is not recommended therapy by guidelines - so not rly on prophylaxis usually)
-CD4 count less than 50 after ruling out disseminated MAC
treatment for primary prophylaxis of mac
azithromycin 1200mg q weekly
clarithromycin 500mg BID
when is primary prophylaxis for mac discontinued
the initiation of effective antiretroviral therapy (according to guidelines)
*CD4 of 30
what are they at risk for
they are starting a new HIV regimen today. what prophylactic regimen should they be put on?
PCP
toxoplasma
MAC
ONLY BACTRIM
starting guideline therapy - do not need prophylaxis for MAC, if they were NOT starting HIV regimen today, would need clarithromycin or azithromycin
HIV patients who have AIDS (CD4 less than 200) should not receive which vaccines
live vaccines - whether bacterial or viral
ALL OTHERS can be given
true or false
TAF and TDF cannot be given together
true
