Term
HIV is a retrovirus subset lentivirus, which means that there is an interval between the initial infection and the onset of symptoms
HIV infects the CD4 T cells and begins to replicate rapidly
gradual deterioration of immune function and eventual destruction of lymphoid and immunologic organs is central to triggering the immunosuppression that leads to AIDS
healthy adults have ~ 1000 CD4
AIDS CD4 < 200
reverse transcriptase copies HIV genome into the DNA of the host cell, genetic material is permanently incorporated into the infected cell genome |
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Definition
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Term
sexual
perinatal
blood: parenteral, occupational exposures, blood products
increased risk: viral load of source, frequency of exposure
rarely: other body fluids, organ transplant
NOT BY: inanimate objects, insect vector, casual contact |
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Definition
| routes of HIV transmission |
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Term
Acute HIV infection:
Day 0 = primary infection
Week 4 = acute retroviral syndrome (flu-like symptoms)
Asymptomatic HIV infection:
Week 6 - 6 Months = detectable antibodies, immunologic control (decrease in CD4 cells), plasma viral load stabilizes, clinical latency
Symptomatic HIV Infection:
Year 5-9 = constitutional illness, virologic progression, immunosuppression
AIDS:
Year 10-12 years = AIDS defining illness
Year 11.5-12 = death |
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Definition
| course of HIV infection without antiretroviral therapy |
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Term
HIV +
AND
CD4 < 200
OR
Defining Illness: opportunistic infections (bacterial, mycobacterial, parasitic, fungal, viral); cancers (kaposi sarcoma, lymphoma, cervical); HIV illness (encephalopathy, myopathy, nephropathy, wasting) |
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Definition
| clinical definition of AIDS |
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Term
Antibody tests: rapid HIV test kit, ELISA, western blot
antibody window: repeat testing should be done at 6 week, 6 months, and 1 year b/c it could take up to one year for antibodies to be produced
antigen test: HIV DNA PCR, HIV RNA viral load
CD4 count |
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Definition
| *diagnostic testing for HIV* |
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Term
whenever the index of suspicion is high: focus on risk activities not risk groups
AIDS defining illness
unexplained immunosuppression
suspicious illnesses: mucocutaneous candidiasis, cervical hyperplasia, acute retroviral syndrome, current or prior STD |
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Definition
| who should get tested for HIV? |
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Term
genotype: tests viral genes for mutations of drug resistance, takes 1-2 weeks
phenotype: tests virus ability to replicate in presence of meds, takes 2-3 weeks, harder to interpret, more expensive
recommended for:
acute HIV infection
chronic HIV infection
virologic failure
pregnant patients |
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Definition
| HIV resistance testing: difference between genotype and phenotype testing and who they are recommended for |
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Term
AIDS defining illness
HIV associated nephropathy
pregnancy
coinfection with HBV and HBV is being treated
if asymptomatic, based on CD4 counts and viral titers, risks and benefits of therapy, and patient willingness to begin treatment
CD4 Count <350 and Plasma HIV RNA levels < 100,000
Treat
CD4 Count <350 and Plasma HIV RNA level >100,000
Treat
CD4 count = 350-500 and Plasma HIV RNA level <100,000
Treatment recommended and should be offered following full discussion of pros and cons with each patient.
CD4 Count = 350-500 and HIV RNA level >100,000
Treatment should be recommended and should be offered following full discussion of pros and cons with each patient
CD4 Count > 500 and HIV RNA level <100,000
Typically defer treatment, but treatment is optional
CD4 Count >500 and HIV RNA level >100,000
treatment optional |
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Definition
| indications for HIV treatment |
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Term
risks:
drug ADRs so decreased QOL
risk of drug resistance
limitation of future drug options
benefits:
control easier to achieve and maintain
delay immunocompromise
lower risk of resistance
reduction of HIV transmission? |
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Definition
| risks and benefits of early HIV therapy |
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Term
risks:
risk of irreversible immunocompromise
increased difficulty in suppressing viral replication
increased risk of HIV transmission
benefits:
avoid ADRs so better QOL
delays drug resistance
preserves future drug options |
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Definition
| risks and benefits of delayed HIV therapy |
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Term
barriers to adherence:
incomplete understanding
side effects
poor communication
concealing disease
drug abuse
poor social situations
unable to travel, make office visits
psychiatric illness
other medical problems
strategies for improving adherence:
assessed and reinforced at every visit
negotiate a treatment plan patient will commit to
find daily triggers to taking medications
simplify food requirements
simplified regimens (BID dosing, lower pill burden)
clearly written instructions, including pictures if possible
pill organizers, pill alarms, pagers
discuss SE before beginning treatment, anticipate and treat them
avoid drug interactions
discuss with patient in a non-judgmental manner
pharmacist-based adherence clinics |
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Definition
| barriers to adherence and strategies to improve adherence |
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Term
zidovudine
didanosine
stavudine
lamivudine
abacavir
tenofovir
emtricitabine
chemically similar to nucleosides
must be phosphorylated to be active
interferes with HIV DNA polymerase |
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Definition
| nucleoside reverse transcriptase inhibitors |
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Term
nevirapine
delavirdine
efavirenz
etravirine
interferes directly with DNA polymerase
no action on mammalian DNA polymerase
no phosphorylation necessary
single mutation leads to CLASS RESISTANCE |
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Definition
| non-nucleoside reverse transcriptase inhibitors |
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Term
saquinavir
indinavir
ritonavir
nelfinavir
amprenavir
lopinavir/ritonavir
atazanavir
fosamprenavir
tipranavir
darunavir
inhibit viral protease which is required for polypeptide cleavage and viral budding
binds to the active site of HIV-1 protease
results in the formation of immature, non-infectious viral particles
pharmacokinetic boosting with ritonavir is required with many PIs. rationale: CYP3A4 interaction, lower doses, lower pill burden, highly potent |
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Definition
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Term
enfuvirtide
synthetic peptide
binds to the HIV-1 transmembrane fusion protein
prevents viral fusion and entry into the cell
SQ injection BID |
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Definition
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Term
maraviroc
CCR5 co-receptor antagonist
prevents HIV from attaching to the surface of CD4 cells with CCR5 receptor
patient must be tested to see if they have the CCR5 receptor |
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Definition
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Term
raltegravir
inhibit the activity of the integrase enzyme to prevent HIV DNA from combining with healthy cell DNA
approved for use in treatment naive patients and treatment resistant patients |
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Definition
| integrase strand transfer inhibitor (INSTI) |
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Term
comorbid conditions
ADRs
drug interactions
pregnancy or pregnancy potential
genotype results
gender and pretreatment CD4 count (if considering nevirapine)
HLA-B*5701 testing (if considering abacavir)
coreceptor tropism assay (if considering maraviroc)
patient adherence potential
convenience (pill burden, dosing frequency, food/fluid considerations) |
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Definition
| factors to consider when selecting initial HIV regimen |
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Term
never monotherapy -> only exception is zidovudine perinatal prophylaxis
avoid sequential monotherapy: in context of virologic failure never change just one medication |
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Definition
| HIV drug selection principles |
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Term
2 NRTI + NNRTI
OR
2 NRTI + PI (preferably boosted with ritonavir)
OR
2 NRTI + INSTI |
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Definition
| recommended initial combination for antiretroviral naive patients |
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Term
advantages:
saves PI and INSTI for future
low pill burden (once daily option)
less lipid SE
disadvantages:
NNRTI resistance in treatment naive patients
low genetic barrier for development of resistance: cross-resistance among NNRTIs
skin rash
drug interactions |
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Definition
| advantages and disadvantages of an initial HIV regimen of 2 NRTI + NNRTI |
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Term
advantages:
saves NNRTI and INSTI for future use
higher genetic barrier to resistance
PI resistance uncommon with failure (boosted PIs)
disadvantages:
compromises future PI regimens
metabolic complications: dyslipidemia, insulin resistance, hepatotoxicity
GI ADRs
drug interactions (ritonavir especially)
higher pill burden |
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Definition
| advantages and disadvantages of an initial HIV regimen of 2 NRTI + PI |
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Term
advantages:
saves PI and NNRTI for future
fewer drug related ADRs and lipid changes than efavirenz
virologic response noninferior to efavirenz
no food effect
fewer drug interactions than PI or NNRTI
disadvantages:
less long term experience in ART naive
lower genetic barrier for development of resistance than boosted PIs
no data with NRTIs other than tenofovir and emtricitabine in ART naive patients
BID dosing required |
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Definition
| advantages and disadvantages of an initial HIV regimen of 2 NRTI + INSTI |
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Term
Efavirenz (NNRTI)
PLUS
Tenofovir (NRTI)
PLUS
Emtricitabine
Efavirenz should not be used during the 1st trimester of pregnancy or in women trying to conceive or not using effective and consistent contraception |
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Definition
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Term
Atazanavir/Ritonavir
PLUS
Tenofovir
PLUS
Emtricitabine
OR
Darunavir/Ritonavir
PLUS
Tenofovir
PLUS
Emtricitabine
Atazanavir/Ritonavir should not be used in patients who require >20mg omeprazole equivalent per day. |
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Definition
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Term
Lopinavir/Ritonavir (PI)
PLUS
Zidovudine (NRTI)
PLUS
Lamivudine (NRTI) |
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Definition
| preferred HIV regimen for pregnant women |
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Term
Raltegravir (INSTI)
PLUS
Tenofovir (NRTI)
PLUS
Emtricitabine (NRTI) |
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Definition
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Term
Abacavir + Lamivudine + Zidovudine +/- Tenofovir: less efficacy (all NRTIs)
Etravirine (NNRTI) regimens: Abacavir (NRTI) + Didanosine (NRTI) OR Abacavir (NRTI) + Tenofovir (NRTI) - lack of data in treatment naive patients
Darunavir (PI): unboosted no data
Saquinavir (PI): unboosted less efficacy
Stavudine (NRTI) + Lamivudine (NRTI): increased toxicity
Didanosine (NRTI) + Tenofovir (NRTI): high risk of failure, rapid rate of resistant mutations, potential for immunologic non-response/CD4 decline
Delaviradine (NNRTI): less efficacy, TID dosing
Enfuvirtide (fusion inhibitor): no data, BID SQ dosing
Indinavir (PI): unboosted TID dosing with meal restrictions
Indinavir (PI): boosted high incidence of nephrolithiaisis
Nelfinavir (PI): inferior, high incidence of diarrhea
Ritonavir as sole PI: GI intolerance, high pill burden
Tipranavir (PI): boosted less efficacy |
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Definition
| drugs to avoid for initial HIV therapy |
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Term
obtain CD4 and HIV RNA titers before starting therapy
optimal virologic response is maximal virologic suppression:
virologic suppression - HIV RNA levels < 48
virologic failure - inability to achieve/maintain HIV RNA levels < 200
incomplete virologic response - 2 consecutive HIV RNA levels > 200 after 24 weeks on ARV therapy
check HIV RNA titers in 2-8 weeks after initiation or change in therapy then q3-4 months
always confirm rising titer with 2nd test |
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Definition
| monitoring and goals of HIV therapy |
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Term
| if D/C one med -> D/C ALL meds at the same time |
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Definition
| correct way to D/C HIV meds |
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Term
antepartum:
combination ART > single-drug regimen
longer duration (begin at 28 weeks gestation) > shorter duration (begin at 36 weeks gestation)
postpartum:
breastfeeding is NOT recommended for HIV infected women |
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Definition
| recommendations for antepartum and postpartum HIV patients |
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Term
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Definition
| what HIV drug should be avoided in the 1st trimester of pregnancy? |
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Term
| Nevirapine (NNRTI) and Lamivudine (NRTI) |
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Definition
| what 2 HIV medications can be added to a pregnant patient or infants regimen in high risk situations? |
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Term
| HIV DNA PCR: tests for viral load where as Western blot and ELISA test for antibodies which will be transferred to the baby from the mother even if the baby is HIV (-) |
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Definition
| what type of HIV test should be used in infants? |
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