HIV Flashcards
3 primary modes of HIV transmission
Sexual
Parenteral (needles)
Perinatal (mother/baby)
Ways to limit risk of transmission
Condoms/safe sex no needle sharing screen blood for contamination HIV treatment during pregnancy do not breastfeed after delivery if safe alternatives are available
Treatment goals of antiretroviral therapy
Maximally and durably suppress viral replication Avoid development of drug resistance Restore and preserve immune function Prevent opportunistic infections Minimize drug adverse effects
HIV RNA
quantifies viremia, helps to monitor disease progression and treatment effectiveness.
Monitor at baseline, after therapy changes, and every 3-4 months
CD4 lymphocyte count
Measures how far the HIV infection has progressed
Measures CD4%, because absolute can vary
Helps decide when to initiate treatment
Should be monitored at diagnosis and every 3-6 months
Indications to start antiretroviral therapy
Any AIDS-defining illness
CD4 count 500, initiation is encouraged
Pregnancy
Treating Hep B Co-infections
Antiretroviral therapy guidelines
Therapy should contain at least 3 drugs in a combination of an NNRTI or a retonavir-boosted PI with two NRTIs or NtRTIs.
3 combo therapy recommendations for treatment-naive patients
NNRTI (efavirenz) + 2 NRTIs (tenofovir + emtricitabine)
Ritonavir-boosted PI (atazanavir+ritonavir or darunavir+ritonavir) + 2 NRTIs (Tenofovir+emtricitabine
Integrase inhibitor (raltegravir) + 2 NRTIs (tenofovir+emtricitabine)
What should be done prior to selecting a new antiretroviral regimen once the patient has failed the original treatment?
Comprehensive review of patient’s severity of disease
Antiretroviral treatment history
Adherence to therapy
intolerance or toxicity
concomitant drug therapies
comorbidities
results of current and past HIV resistance testing
Nucleoside Reverse Transcriptase Inhibitors (NRTI) MOA
Prevents conversion of RNA to DNA by inhibiting reverse transcriptase
NRTI drugs
Ziagen - abacavir (ABC) Emtriva - emtricitabine (FTC) Epivir - lamivudine (3TC) Viread - tenofovir (TDF) Retrovir - zidovudine (AZT, ZDV)
NRTI class ADRs
Lactic acidosis/hepatic steatosis
pancreatitis - discontinue HAART and treat
Lipodistrophy (only seen with tesamorelin/Egrifta)
Ziagen/abacavir-specific BBW
Serious, sometimes fatal hypersensitivity reaction!! - test patients for HLA-B*5701 allele. If positive, pt has 70% likelihood of having a reaction
NRTI Class general BBWs
Lactic acidosis
Acute, severe exacerbations of HBV following discontinuation of HAART, do not use in pts with concomitant HBV
Retrovir/zidofudine-specific BBWs
hematologic toxicity (neutropenia and severe anemia) mypoathy with prolonged use
Which NRTI’s should be used with caution in patients with hepatic impairment?
Ziagen/abacavir
Viread/tenofovir
Retrovir/zidovudine
Which NRTIs should be used with caution in patients with renal impairment
Emtriva/emtricitabine
Epivir/lamivudine
Viread/tenofovir
Retrovir/zidovudine
Non-Nucleoside Reverse Transcriptase Inhibitor (NNRTI) MOA
binds to reverse transcriptase, blocking DNA polymerase activities including replication
NNRTI Class ADRs
Rash including SJS Drug interactions (3A4 is major!! also 2C19 and 2C9)
NNRTI drugs
Sustiva - efavirenz (EFV)
Intelence - etravirine (ETR)
Edurant - rilpivirine (RPV)
Sustiva/efavirenz contraindications
significant hypersensitivity (including SJS) concurrent use of bepridil, cisapride, midazolam, pimozide, triazolam, St. John's Wort, or ergot alkaloids
Sustiva/efavirenz side effects
CNS effects
fat redistribution
hypercholesterolemia
immune reconstitution syndrome
rash
use with caution in patients with seizure disorder
not recommended for patients with hepatic impairment
Intelence/etravirine ADRs
fat redistribution
immune reconstitution syndrome
skin reactions/hypersensitivity (SJS)
Edurant/rilpivirine contraindications
concurrent use of carbamazepine, dexamethasone (more than 1 dose), oxcarbazepine, phenobarb, phenytoin, PPIs, rifabutin, rifampin, rifapentine, or St. John’s Wort
Edurant/rilpivirine ADRs
Depressive disorders Fat Redistribution Hepatotoxicity Immune reconstitution syndrome QT prolongation
what drugs make up Truvada
tenofovir and emtricitabine (2NRTIs)
What drugs make up Atripla
tenofovir, entricitabine, and efavirenz (NNRTI + 2NRTIs)
What drugs make up Complera
tenofovir, rilpivirine, and emtricitabine (NNRTI + 2 NRTIs)
Integrase inhibitors MOA
Inhibit catalytic activity of integrase, preventing integration of proviral gene into human DNA
Integrase inhibitors Class ADRs
Rifampin and etravirine decrease raltegravir
Omeprazole increases raltegravir
Integrase inhibitor drugs
Issentress - raltegravir (RAL)
Stribild - elvitegravir (EVG) (co-formulated with cobicistat, tenofovir, and emtricitabine)
Stribild/elvitegravir BBWs
CI in concurrent use of afluzosin, cisapride, ergot derivatives, lovastatin, midazolam, pimoxide, rifampin, sildenifil, simvastatin, triazolam, and SJW
Lactic acidosis
exacerbations of HBV with discontinuation
Protease Inhibitor (PI) MOA
inhibits cleavage of viral polyprotein precursors into individual functional proteins required for infectious HIV
PI Class ADRs
bleeding - avoid in hemophiliacs or with anticoagulants
hyperlipidemia, insulin resistance/diabetes, increased LFTs, lipodystrophy, decreased bone mineral density
PI Drugs
Reyataz - atazanavir (ATV)
Prezista - darunavir (DRV)
Kaletra - lopinavir + ritonavir (LPV/r)
Reyataz contraindications
hypersensitivity
3A4 inducers
Prezista contraindications
coadministration with other 3A4 substrates
Kaletra contraindications
hypersensitivity
3A4 substrates
how is ritonavir (Norvir) used in therapy?
it is a “booster” for PIs
how does ritonavir affect the CYP system?
potent 3A4 inhibitor and substrate
2D6 substrate
has mixed dose-dependent induction and inhibition of other phase 1 and 2 enzymes
Fuzeon (enfuviritide) MOA
binds to the first heptad-repeated in the gp41 subunit of viral envelop glycoprotein. inhibits fusion of HIV virus with CD4 cells by blocking the conformational change in gp41 required for membrane fusion and entry into cell
Fuzeon drug interactions
NONE
Fuzeon BBW/ADRs
Hypersensitivity immune reconstitution syndrome injection site reactions pneumonia use caution in patients with coagulation disorders or receiving anticoagulants - increased risk of bleeding at injection site do not use in ART-naive patients
CCR5 antagonist MOA
selectively and reversibly binds to chemokine coreceptors located on human CD4 cells. prevents interaction between human CCR5 coreceptor and the gp120 conformation change required for HIV fusion with CD4 cell and subsequent cell entry
CCR5 drugs
Selzentry - maraviroc (MVC)
Selzentry drug interactions
3A4 inducers and inhibitors
Selzentry BBW
possible drug-induced hepatotoxicity with allergic type features has been reported
Selzentry ADRs
immune reconstitution syndrome infections postural hypotension skin and hypersensitivity reactions use with caution in CV disease use with caution in hepatic impairment renal impairment increases drug concentrations
