IC18a PR3151 HIVAIDS Flashcards
describe HIV and what it does to the body (general)
lentivirus group of the retrovirus family
attacks the CD4 t cells
causes AIDS in the long term
Describe the mode of transmission of HIV
through specific fluids: genital fluids, blood, breast milk:
- sexual intercourse
- sharing of infected syringes and needles
- Mother-to-child transmission
- transfusion w/ contaminated blood
What patient populations/types should be tested for HIV?
1) individuals with unprotected sex with multiple sex partners
2) male-male sexual intercourse
3) intravenous drug users
4) recipient of multiple blood infusions
5) commercial sex workers
6) pregnant women
7) testing for STIs
8) sexual assault victims
What are the two diagnosis methods for HIV?
serum antibody detection
-Western blot
-enzyme immunoassay
hiv rna detection and quantification (viral load)
-PCR
What are the presentation stages for HIV?
1) acute infection
2) asymptomatic
3) persistent generalised lymphadenopathy
4) aids and related infections
What is the clinical presentation of HIV during the acute (primary) infection stage?
2-3 weeks of symptoms: fever, malaise, rash, swollen lymph nodes
What is the clinical presentation of HIV during the asymptomatic stage?
asymptomatic for many years
What is the clinical presentation of HIV during the persistent generalised lymphadenopathy stage?
> 3 months of persistent unexplained lymph node swelling at neck, groin, underarms
What is the clinical presentation of HIV during the AIDs and related conditions stage?
AIDS = CD4 < 200/mm3
symptoms of: fever, unexplained weight loss, diarrhoea, swollen lymph nodes
multi-organ involvement
aids defining conditions:
- lymphoma, kaposi sarcoma, pneumocystis pneumonia, aids dementia complex, cytomegalovirus.
what are the primary goals of antiretroviral therapy?
Reduce HIV-associated morbidity and mortality
Prolong the duration and quality of survival
Restore and preserve immunologic function
Maximally and durably suppress plasma HIV viral load
Prevent HIV transmission
what are the two surrogate markers for HIV?
cd4 and viral load
CD4 surrogate marker useful for?
used to measure the
1) subsequent disease progression
2) immune function
3) response to treatment
4) when to START or STOP prophylaxis to opportunistic infections, e.g., pneumocystic pneumonia prophylaxis when cd4 <200/mm3
how often to recheck cd4 after treatment initiation?
measure 3-6 months after
every 12 months after adequate
viral load surrogate marker useful for?
assessing the response to treatment
how often to check for viral load?
2-4 weeks after treatment initiation
6-8 weeks thereafter
(should take 8-24 weeks for viral suppression)
once viral suppression is reached, can be tested every 3-6 months
when to start hiv art?
initiate as soon as possible regardless of cd4 count to reduce mortality and morbidity AND prevent HIV transmission
what are the benefits of earlier ART?
maintain high cd4 count and potentially irreversible damage to the immune system
decrease risk for hiv associated complications that can occur at cd4+ counts >350/mm3 e.g., TB, non-hodgkin lymphoma, kaposi sarcoma, peripheral neuropathy, hiv associated cognitive impairment
Decreased risk of non-opportunistic conditions, including cardiovascular disease, renal disease, liver disease, and non–AIDS-associated malignancies and infections
Decreased risk of HIV transmission to others, which will have positive public health implications
>350, some of these opportunistic infections MAY occur, so treat ear
what are the LIMITATIONS of earlier ART?
Development of treatment-related side effects and toxicities
Development of drug resistance because of incomplete viral suppression, resulting in loss of future treatment options
Transmission of drug-resistant virus in patients who do not maintain full virologic suppression
Less time for the patient to learn about HIV and its treatment and less time to prepare for the need for adherence
Increased total time on medication, with a greater chance of treatment fatigue
Increased cost
factors to consider before starting ART regimen
Regimen selection should be individualized and should be based on a number offactors, including:
Patient’s understanding of HIV
Cost and availability
Adherence issues, convenience
pill burden
dosing frequency
food and fluid considerations
Virologic efficacy
Potential adverse effects (comorbidities, drug interactions)
Childbearing potential
Genotypic drug resistance testing 19
what is the life cycle of HIV?
free virus -> binding and fusion –> infection –> reverse transcription –> integration –> transcription –> assembly –> budding –> maturation
What are the two recommended ART regimens?
2 NRTI + 1 INSTI
- tenofovir + emtricitabine + bictegravir (TEB)
- tenofovir + emtricitabine + dolutegravir (TED)
- abracavir + lamivudine + dolutegravir (ALD)
1 NRTI + 1 INSTI
- tenofovir + dolutegravir
when is dual therapy (INSTI + NRTI) for ART not recommended?
1) for patients w/ HIV RNA >500,000 copies/ml
2) HBV coinfection
3) ART to be started before HIV genotypic resistance testing results or HBV testing are available
what are the NRTI drugs?
tenofovir (tin of ears)
emtricitabine (electricity bone)
abacavir (abc cadaver)
zidovudine (zombie divin)
lamivudine (lamb voodoo)
what are the advantages to using NRTI?
renal elimination
little concern for drug interactions
what are the disadvantages to using NRTI?
somedrugs are better than others in this class? list the special cases
mitochondrial toxicity (rare)
- lactic acidosis and hepatic steatosis (fatty infiltrates)
- lipoatrophy (loss of fat)
zidovudine > others (similar; no emtricitabine)
ALL REQUIRE RENAL DOSE ADJ EXCEPT ABACAVIR
what is the adverse effect to using lamivudine
Lamivudine –minimal toxicity, nausea/vomiting/diarrhea (N/V/D)
what is the adverse effect to using emtricitabine
Emtricitabine–minimal toxicities, hyperpigmentation, nausea, diarrhoea
what is the adverse effect to using tenofovir
Tenofovir: –N/V/D, can cause renal impairment, decrease in bone mineral density
what is the adverse effect to using abacavir
Abacavir–N/V/D, Hypersensitivity reaction in patients with HLA-B5701. Symptoms incl: rash, fever, rash, malaise or fatigue, loss of appetite, sore throat, cough, shortness of breath. Can be fatal. Discontinue if it occurs, do not rechallenge. Testing for absence of HLA-B5701 is recommended before initiating abacavir.
Concern for association with myocardial infarction –not be used in high cardiovascular risk patients.
what is the adverse effect to using zidovudine
Zidovudine –N/V/D, myopathy, bone marrow suppression causing anemia or neutropenia.
what are the INSTI drugs?
bictegravir
dolutegravir
raltegravir
elvitegravir
what are the advantages to using INSTI?
well tolerated, good virologic efficacy
BD>RE (barrier to genetic resistance)
what are the disadvantages to using INSTI? (ADR and DDI)
side effects:
- nausea, headache, weight loss, diarrhoea
- psych patients may develop suicidal ideation and depression
ddi:
- BDE are substrates of 3A4
- BA of drugs lowered with concurrent administration polyvalent cations
what is the adverse effect to using bictegravir
increase serum creatinine (inhibit tubular secretion of creatinine) but no effect on glomerular function
what is the adverse effect to using raltegravir
increase creatinine kinase (rhabdomyolysis), pyrexia
what is the adverse effect to using dolutegravir
increase serum creatinine (inhibit tubular secretion of creatinine) but no effect on glomerular function
what are the NNRTI drugs?
efavirenz
and
rilpivirine
what are the advantages to using NNRTI?
long half life
less metabolic toxicity (hyperlipidemia, insulin disorder) vs PIs
what are the disadvantages to using NNRTI?
lower barrier to genetic resistance
cross resistance
skin rash risk, SJS (R < E)
QTC prolongation
what is the adverse effect to efavirenz
Efavirenz –rash, hyperlipidemia, neuropsychiatric SE(dizziness, depression, insomnia, abnormal dreams,hallucination), increase in LDL-C and triglycerides, hepatotoxicity
PK of efavirenz and rilpivirine
Efavirenz –CYP 3A4 substrate,
CYP2B6 and 2C19 inducer
Rilpivirine - CYP 3A4 substrate, oral absorption is reduced with increased gastric pH; use with PPIs is contraindicated.
what is the adverse effect of rilpivirine
Rilpivirine–depression, headache
what are the PI drugs?
RLAFD
ritonavir
liponavir
atazanavir
darunavir
fosamprenavir
what are the advantages to using PI?
high genetic barrier to resistance
what are the disadvantages to using PI?
Metabolic complications (dyslipidemia, insulin resistance)
GI: NVD
Liver toxicity (especially with chronic hepatitis B or C)
CYP3A4 inhibitors and substrates: potential for drug interactions
Fat maldistribution (Lipohypertrophy)
Increased risk of osteopenia/osteoporosis
what is the additional properties and adverse effect of ritonavir
potent CYP3A4, 2D6 inhibitor; frequently combined with other PI to “boost” their levels (egLopinavir/ritonavir).
Additional SE: paresthesia(numbness of extremities), taste perversion
what is the additional properties and adverse effect of darunavir
good GI tolerability, less lipids effects.
Additional SE: Skin rash (10%), concern for SJS (it is a sulphonamide)
what is the additional properties and adverse effect of atazanavir
good GI tolerability, less lipids effects.
Absorption depends on low pH (contraindicated concurrent use with PPIs).
Additional SE: hyperbilirubinemia, prolong QT interval, skin rash
what are the fusion inhibitor drugs? include route and freq
enfuvirtide IM BD
what is the adverse effect of enfuvirtide
Injection site reaction (erythema/induration, nodules/cyst, pruritis, ecchymosis in 98%),
rare hypersensitivity reaction reported (fever, rash, chills, decrBP).
Increased bacterial pneumonia.
what are the CCR5 antagonist drugs?
maraviroc
when and how should maraviroc be used?
used only in people whose strain of HIV uses the CCR5 receptor to enter the CD4 cells.
Need co-receptor tropism assay before initiation
what is the adverse effect of maraviroc
ADR-Abdominal pain, cough, dizziness, musculoskeletal symptoms, pyrexia, rash, upper respiratory tract infections, hepatotoxicity, orthostatic hypotension.
cyp3a4
what are the strategies to improve adherence to ARTs?
Establish readiness to start therapy
Provide education on medication dosing
Review potential side effects
Anticipate and treat side effects
Utilize educational aids including pictures, pillboxes, and calendars
Engage family, friends
Simplify regimens, dosing, and food requirements (taking ARV with or without food)
Utilize team approach with nurses, pharmacists, and peer counselors
Provide accessible, trusting health care team 37
which NRTI does not need renal dose adjustment?
ABACAVIR
which NRTI can be used in pregnancy
Zidovudine
special properties of ritonavir
is used as a pk enhancer along with cobicistat to increase the concentration of ARV (PIs, elvitegravir)
- p450 3a inhibitors
