HIV Flashcards
What type of virus is HIV?
a single-stranded RNA retrovirus that uses the machinery in CD4+ T Helper cells to replicate
What is the treatment called for HIV?
Antiretroviral therapy (ART)
When HIV continues to replicate, what increases and what decreases?
viral load increases,
CD4+ count decreases
When is AIDS diagnosed?
when the CD4+ count fall below 200cells/mm3 or by the presence of an AIDS-defining condition
How is HIV transmitted?
Blood, semen, pre-seminal fluid, vaginal fluid, rectal fluids, and breast milk.
Most infection is caused by vaginal and rectal sex,, sharing needles.
Can HIV be spread from a woman to her child?
Yes - pregnancy, childbirth, or breast milk. This is called “vertical” transmission
The CDC recommends routine HIV screening for who?
How often should a high-risk person be tested?
EVERYONE (13-64) at least once
annually
What are high-risk indicators for becoming infected with HIV?
sharing needles
High- risk sexual behaviors
History of a STI or hepatitis or TB
How long does the acute infection (stage 1) last?
2-4 weeks; a person is HIGHLY contagious in this stage; very common sx, why sometimes it is missed
How long after initial infection does it take for the viral load to be high enough for HIV RNA and HIV p24 antigens to be detected with an initial HIV1/HIV2 antigen/antibody screening test?
~2 weeks post-infection
Positive results are confirmed with an antibody differentiation immunoassay which can determine if HIV1 or HIV2; detection in 4-6 weeks, but sometimes 6 moths
The OTC kit that provides immediate results by detecting the pretense of HIV Ab is the:
OraQuick in-home HIV test
Should be used >3 months from exposure due to the lab in Ab production (earlier can cause a false negative)
HIV Life Cycle: what happens during Stage 1?
This stage is called: Binding/Attachment
HIV binds (attaches itself) to receptors on the surface of a CD4 cell
Where do Maraviroc and Ibalizumab-uiyk work? What stage?
Stage 1
CCR5 antaognist
Post-attachment inhibitors
HIV Life Cycle: what happens during Stage 2?
“Fusion”
The HIV envelope and the CD4 cell membrane fuse, which allows HIV to enter the CD4 cell
Where does Enfuvirtide work? What stage?
Stage 2: Fusion inhibitor
HIV Life Cycle: what happens during Stage 3?
“Reverse Transcription”
inside the CD4 cell, HIV releases and uses reverse transcriptase (an HIV enzyme) to convert its genetic material- HIV RNA into HIV DNA.
The conversion of HIV RNA to HIV DNA allows HIV to enter the CD4 cell nucleus and combine with the cell’s genetic material- cell DNA.
NNRTs & NRTs work here
HIV Life Cycle: What happens during stage 4?
“Integration”
Inside the CD4 cell nucleus, HIV releases integrate (an HIV enzyme).
HIV uses integrate to insert (integrate) its viral DNA into the DNA of the CD4 cell.
What drugs work during the integration stage?
Integrase strand transfer inhibitors (INSTIs)
HIV Life Cycle: What happens during stage 5?
“Replication”
Once integrated into the CD4 cell DNA, HIV begins to use the machinery of the CD4 cell to make long chains of HIV proteins.
The protein chains are the building blocks for more HIV
No drugs work here.
HIV Life Cycle: What happens during stage 6?
“Assembly”
New HIV proteins and HIV RNA move to the surface of the cell and assemble into immature HIV (noninfectious) HIV
HIV Life Cycle: what happens during stage 7?
“Budding and Maturation”
Newly formed immature (noninfectious) HIV pushes itself out of the host CD4 cell.
The new HIB release protease (an HIV enzyme). Protease breaks up the long protein chains in the immature virus, creating the mature (infectious) virus
Where do protease inhibitors work? What stage?
Stage 7, the last stage
What lab value is used to determine the need for OI prophylaxis?
CD4 count
Treatment goal is 800-1200cells/mm3
This lab test indicates how much HIV RNA is in the blood. It is the most important indicator of response to ART
HIV Viral Load
What does a high viral load indicate?
medication non adherence or drug resistance. The treatment goal is an undetectable HIV viral load
What drug requires HLA-B*5701 allele screening?
Abacavir
*NEVER re-challenge
What drug requires a tropism assay?
Maraviroc
the CCR5 receptor must be ONLY present. drug not useful is the CxCR4 coreceptor is present.
Who is ART recommended for?
ALL HIV-infected individuals
to reduce progression and prevent transmission to partners; it should be started as soon as possible
Adherence for ART must be >%?
> 95%; missing no more than 1 dose per month with a once-daily regimen
Recommended regimens for initial ART in most treatment-naive adults that are ONE pill, ONCE daily (3 drugs)
Biktarvy
Triumeq
Dovato
Recommended regimens for initial ART in most treatment naive adults that are TWO pills, ONCE daily (4 regimens)
Tivicay + Truvada
Tivicay + Descovy
Isentress + Truvada
Isentress + Descovy
What is the combination therapy of the one pill once daily ART?
2 NRTI + 1 INSTI (Biktarvy, Triumeq)
OR
1 NRTI + 1 INSTI (Dovato)
What is the combination therapy of the two pills once daily ART?
INSTI (by itself) + 2 NRTI in a combo tablet (Truvada or Descovy)
When should you not use Tenofovir DF?
High fracture risk (low bone mineral density)
If using, consider a calcium and vitamin D supplementation
When should you not start Dovato?
If the HIV RNA >500,000 copies/mL
&
if there is a hepatitis B virus co-infection
Brand: Biktarvy
Generic: Bictegravir/ Emtricitabine/ Tenofovir alafenamide
DONT USE IN RENAL IMPAIRMENT; add on calcium vitamin D supplement
Brand: Triumeq
Generic: Dolutegravir/ Abacavir/ Lamivudine
HLA-B5701 ALLELE TEST before starting* –> indicates a higher risk of having a severe hypersensitivity reaction
Brand: Dovato
Generic: Dolutegravir/ Lamivudine
*DO NOT start if HIV RNA >500,000 or if there is a HBV co-infection
Brand: Tivicay + Truvada
Tivicay = Dolutegravir
Truvada = Emtricitabine/ Tenofovir disoproxil fumarate (TDF)
Brand: Tivicay + Descovy
Tivicay = Dolutegravir
Descovy = Emtricitabine/ Tenofovir aladenamide (TAF)
Brand: Isentress + Truvada
Isentress = Raltegravir
Truvada = Emtricitabine/ Tenofovir disoproxil fumarate (TDF)
Brand: Isentress + Descovy
Isentress = Raltegravir
Descovy = Emtricitabine/ Tenofovir aladenamide (TAF)
TDF/ Viread TAF Epivir/Lamivudine Emtriva/ emtricitabine Ziagen/ Abacavir Retrovir/ zidovudine
What drug class?
Nucleoside(tide) reverse trancsriptase inhibitors (NRTIs)
Dec dose with renal impairment! (except abacavir)
What is the mechanism of action for NRTIs?
All HIV drugs block viral replication.
NRTIs are similar to nucleoside/tides and competitively block/inhibit reverse transcriptase enzyme. This enzyme converts RNA into DNA (reverse transcription)
Stage 3!
What NRTI is given IV during labor to protect the baby if the mother’s viral load is >1,000 copies/mL?
zidovudine/ Retrovir
Older NRTIs (didanosine, zidovudine, and stavudine) have higher risk of …
lactic acidosis and hepatomegaly with steatosis (fatty liver)
Which drugs have a warning for lactic acidosis (not boxed warning)
abacavir, tenofovir, lamivudine
Which drugs have a warning for hepatomegaly with steatosis?
abacavir, tenofovir, lamivudine
NRTIs treat HIV, some NRTIs treat HBV - would you want to discontinue NRTIs if HBV+?
NO! without adequate HBV treatment, discontinuation can cause acute HBV exacerbation
Which NRTI do you not use if treating both HIV/HBV?
abacavir
Warnings: pancreatitis, severe hepatomegaly with steatosis
Stavudine and didansone
Warnings: myopathy, neutropenia, ANEMIA
zidovudine
treat anemia with erythropoietin; must have ferritin >100ng/mL, TSAT >20% for tx to be effective
These NRTIs can cause lipodystrophy (body gat redistribution, from arms/legs/face to stomach/upper back- buffalo hump/breasts)
stavudine, didanosine, zidovudine
These NRTIs can cause irreversible peripheral neuropathy
stavudine and didanosine
& stavudine can cause hyperbilirubinemia - both drugs not recommended for use
All NRTIs cause what kinds of side effects?
nausea, diarrhea
lamivudine & emcitritabine- headache
Emctricitabine can be replaced with
lamivudine, but NOT used together
Do not use tenofovir formulation with:
Adefovir (HBV)
monitor for TDF side effects and renal damage when used with HCV drugs like Harvoni, Epclusa and Vosevi (HCV)
Do not use Stribild with:
Harvoni (HBV)
Bictegravir
Elvitegravir
Dolutegravir
Raltegravir
“-tegravir”
Drug class?
Integrase Strand Transfer Inhibitors (INSTI)
What is the MOA for INSTI?
Block the integrase enzyme, preventing viral DNA from integrating into the cost cell DNA
Stage 4!
No __ or __ at same time as INSTIs; must separate 2 hours before or 6 hours after
Aluminum or magnesium
This INSTI has a small risk of neural tube defects in pregnancy (is a preferred drug in preg due to strong viral suppression and high barrier to drug resistance), hypersensitivity reaction with severe rash and organ dysfunction, including hepatotoxicity
dolutegravir/ Tivicay
*can also inc SCr by inhibiting tubular secretion (bictegravir also has this same note)
This INSTI has a warning for severe rash and MYOPATHY (inc CPK)
raltegravir/ Isentress
This HIV drug class has side effects that include headache, insomnia, diarrhea and weight gain
INSTIs
efavirenz/ Sustiva rilpivirine/ Edurant doravirine/ Pifeltro nevirapine/ Viramune etravirine/ Intelence delvairdine
What drug class?
Non-nucleoside reverse transcriptase inhibitors (NNRTIs)
NNRTI mechanism of action
NRTIs and NNRTIs inhibit the reverse transcriptase enzyme, but differently:
while NRTIs compete for the binding site, NNRTIs bind to the enzyme non-competitively, causing a conformational change that inhibits the enzyme
Stage 3
This NNRTI must be taken with water and a meal (not substituted with a protein drink), and requires acidic environment for absorption: do not use with PPIs or H2RAs and antacids
rilpivirine/ Edurant
*also warning for depression
& do not use if viral load >100,000 copies/mL and/or CD4+ counts <200 (higher failure rate)
This NNRTI is taken on an empty stomach at bedtime to decrease CNS effects
efavirenz/ Sustiva
Why is Atripla no longer first line?
Atripla (efavirenz/emtricitabine/tenofovir)-
due to CNS/psych issues with efavirenz, still used often
all NNRTIs can cause…
hepatoxicity and severe rash (boxed warning)
nevirapine is worse for hepatotoxicity and rash
Brand: Sustiva
Generic: efavirenz
think psych
Brand: Edurant
Generic: rilpivirine
think acidic environment/ NO PPIs
atazanavir/ Reyataz
darunavir/ Prezista
fosamprenavir/ Lexiva
indinavir/ Crixivan
“end in -navir”
What HIV drug class?
Protease Inhibitors
*NOT first line anymore due to METABOLIC PROBS (hyperglycemia/insulin resistance, dyslipidemia), inc body fat, inc CVD risk, drug interactions AF
Protease Inhibitors MOA
inhibits the protease enzyme which prevents protein strands from being cut into the smaller pieces needed for assembly of new visions. HIV continues to replicate, but produces immature visions that are not infectious
Stage 7
Which PIs are given with a boost (ritonavir or coibistat)
atazanavir and darunavir
Which PI needs an acidic gut for absorption?
atazanavir
PIs should be taken with food to decrease GI upset, except:
fosaprenavir
lopinavir/ritonavir
Due to the high alcohol content of Kaletra and ritonavir, which meds should not be taken with either solution?
metronidazole, tinidazole, disulfram
This PI has a boxed warning for hepatitis/hepatic decompensation and intracranial hemorrhage
tipranavir
all PIs have warnings for
hepatic effects and hypersensitivity
Which PIs are used in caution with sulfa
darunavir, fosamprenavir, tipranavir (inc risk of SJS)
All PIs have side effects of:
diarrhea, nausea
Indinavir has a metallic taste side effect
PIs are strong inhibitors of CYP3A4;
CYP3A4 inducers will decrease PI and could make the ART resistant to treatment. DO NOT use the following drugs with PIs:
Alfuzosin Colchicine Dronedarone, Amiodarone Apixaban, edoxaban, rivaroxaban DAAs, hormonal contraceptives Lovastatin, simvastatin (use atorvastatin or rosuvastatin)
List Boosters/enhancers
ritonavir/ Norvir
cobicistat/ Tybost
Take with food!!! NOT interchangeable or together
Which booster?
Do not use with colchicine, vorconazole
cobicstat
Which boosteR?
do not use with alprazolam, amiodarone, dronedarone, itraconazole
ritonavir
Which drugs are cobicstat in?
Stribild Genvoya Symtuza Evotaz Prezcobix
This entry and attachment inhibitor is a CCR5 antagonist that blocks HIV from binding to the CCR5 co-receptor on the CD4+ cell, which prevents HIV from entering the cell (stage 1)
Maraviroc, MVC (Selzentry)
This entry and attachment inhibitor is a fusion inhibitor, it prevents HIV from fusing to the CD4+ cell membrane, which prevents entry into the cell (stage 2)
enfuviritde, T20 (Fuzeon)
powder for inj - requires reconstitution, self-injected
This entry and attachment inhibitor that is a CD4+ directed post-attachment HIV1 inhibitor & is as a monoclonal antibody works by binding to CD4 cell to block HIV entry (stage 1)
ibalizumab-uiyk (Trogarzo)
A debilitating condition with lipoatrophy, loss of muscle mass, loss of appetite and diarrhea
HIV wasting syndrome - cannabis related drugs: dronabinol (Syndros), nalibone, megestrol (Megace ES) can help
diarrhea - treatment includes anti-diarrheals and fluids/electrolytes
A paradoxical worsening of either a new or known condition that has been suppressed but becomes unmasked after ART is started or treatment is changed to a more effective regimen
IRIS: immune reconstitution inflammatory syndrome
- more likely to occur when CD4 count low, viral load high
- self-treated, ART should be continued and the unmasked condition should be treated
Pregnant women can start/use HIV meds, but avoid breastfeeding (transfer);
recommendations if treatment-naive:
two NRTIs +
(abacavir/lamivudine) (TDF/emtricitabine or lamivudine)
a boosted PI
(atazanavir or darunavir with ritonavir)
OR INSTI (raltegravir or dolutegravir*)
*risk of neural tube defects
What are two other ways to reduce HIV infection risk before or after sexual activity?
PrEP and PEP
Taking a 2-drug combination to prevent infection from a high-risk behavior. Taken BEFORE activity. 1 tab with 2 drugs
PrEP
-person needs to be HIV negative with Ab test
follow-up every 3 months/90 day supply
AFTER HIV-exposure, within 72 hours. taken for 28 days. More drugs needed.
PEP
emergency situations only
Drugs for PrEP
Truvada or Descovy
Drugs for PEP
Truvada (CrCl >60) + Tivicay or Isentress
Brand: Complera
Generic: rilpivirine/TDF/emtricitabine
-water & meal, acidic gut, CI PPIs
Brand: Odesfsey
Generic: rilpivirine/emtricitabine/TAF
Brand: Triumeq
Generic: dolutagravir/abacavir/lamivudine
Brand: Epzicom
Generic: abacavir/lamivudine
Brand: Norvir
Generic: ritonavir
Brand: Prezista
Generic: darunavir
Brand: Reyataz
Generic: atazanavir
Brand: trogarzo
generic: ibalizumab-uiyk
