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HIV

Key Concepts:

Terms in this set (91)

HIV definition
RNA retrovirus that attacks the immune system, mainly the CD4+ T-helper cells
Major indicator for immune function
CD4+ counts and they serve as a key factor in determining both the urgency of antiretroviral theapy (ART) initiation and the need for prophylaxis against opportunistic infections (OIs)
HIV monitoring
Plasma HIV-1 RNA (viral load) should be measured in all HIV-1 infected patients at baseline and on a regular basis thereafter, especially in patients who are on treatment, because viral load is the most important indicator of response to antiretroviral therapy
viral load
quantifies the degree of viremia by measuring the amount of HIV RNA in the blood and is used to assess response to drug therapy, disease progression (along with CD4+ count) and possible medication adherence problems or drug resistance
HIV transmission
through infected blood, semen, vaginal secretions
Vertical transmission
from mother to child, either during pregnancy at birth or through breastfeeding
HIV Ab
Anti-HIV antibodies (HIV Ab) are undetectable during an acute HIV infection however HIV RNA and HIV p24 antigen will be present. HIV Ab test will become positive about 4 to 8 weeks from contracting the disease (may take up to 6 months)
HIV diagnosis
Diagnosis of HIV is confirmed when both the HIV screening and supplemental tests are postive
primary goals of ART
restore and preserve the immune system, suppress HIV viral load to undetectable levels, reduce HIV-associated morbidity, prolong survival, and prevent HIV transmission
ART recommendation
ART is recommended in ALL HIV-infected individuals but the strength of the recommendation varies depending on the patient's baseline CD4+ count and/or presence of certain comorbid conditions (i.e. pregnancy, low CD4+ counts, acute OIs, history of AIDs defining illness)

ART is also recommended for HIV-infected individuals for the prevention of HIV transmission to non-HIV infected sexual partners
ART adherence
Patients need to be advised that they need to have an adherence rate of 95% or higher in order for their ART regimen to be effective long-term (no more than 1 missed dose per month for patients on once daily regimens)
HIV life cycle and site of action of antiretroviral
stage 1: binding (also called attachment)
- CCR5 antagonist
stage 2: fusion
-Fusion inhibitor
stage 3: reverse transcription
-NRTIs and NNRTIs
stage 4: integration
-Integrase Strand Transfer Inhibitors (INSTIs)
stage 5: transcription and translation
stage 6: assembly
-Protease inhibitors
stage 7: budding
NNRTI-Based regimen preferred
efavirenz/tenofovir/emtricitabine
PI-Based regimen preferred
Atazanavir + ritonavir + tenofovir/emtricitabine
Darunavir + ritonavir + tenofovir/emtricitabine
INSTI-Based regimen preferred
Dolutegravir + abacavir/lamivudine
Dolutegravir + tenofovir/emtricitabine
Elvitegravir/Cobicistat/tenofovir/emtricitabine
raltegravir + tenofovir/emtricitabine
NRTI boxed warnings
all NRTIs have a boxed warning for lactic acidosis and severe hepatomegaly with steatosis, sometimes fatal
Ziagen generic name
Abacavir
Epzicom generic name
Abacavir + lamivudine
Abacavir boxed warning
serious, sometimes fatal, hypersensitivity reaction-- look for fever, skin rash, respiratory symtpoms (dyspnea, cough). Discontinue drug and do not rechallenge

Must screen for the HLA-B*5701 allele prior to starting abacavir therapy-- if positive, increase risk for hypersensitivity reaction so do not use. Record abacavir allergy in patient record.
Abacavir class
NRTIs
Emtriva generic name
emtricitabine
Emtricitabine class
NRTI
Truvada generic
emtricitabine + tenofovir
Atripla generic
emtricitabine + tenofovir + efavirenz
Complera generic
emtricitabine + tenofovir + rilpivirine
Stribild generic
emtricitabine + tenofovir + elvitegravir and cobicistat
Emtricitabine dosing
capsules: 200 mg daily
Truvada dosing
1 tab daily without regards to food
Atripla dosing
1 tab daily

Take on an empty stomach, preferably at bedtime.
Complera dosing
1 tab daily with a meal
Stribild dosing
1 tab daily with food
Emtricitabine boxed warning
may exacerbate Hepatitis B once drug is discontinued or when HBV resistance develops
Emtricitabine side effects
hyperpigmentation, rash
lamivudine class
NRTI
Epivir generic
lamivudine
Epzicom generic
lamivudine + abacavir
lamivudine boxed warning
do not use Epivir-HBV for treatment of HIV (contains lower dose of lamivudine)

may exacerbate HBV once drug is discontinued or when HBV resistance develops
Tenofovir class
NRTI
Viread generic
tenofovir
tenofovir dosing
300 mg daily
tenofovir boxed warning
may exacerbate HBV once drug is discontinued or when HBV resistance develops
tenofovir side effects
renal insufficiency, Fanconi's syndrome, osteomalacia and decrease bone density
NNRTI warnings
ALL NNRTIs can cause rash including SJS/TEN and hepatoxicity
Sustiva generic
efavirenz
efavirenz dosing
600 mg daily on an empty stomach, preferably at bedtime
efavirenz side effects
CNS (impaired concentration, somnolence, vivid dreams--usually resolve within 2-4 weeks) and psychiatric symptoms (depression, paranoia, mania, suicide), rash
efavirenze pregnancy category
D
Rilpivirine, RPV class
NNRTI
Edurant generic
Rilpivirine
rilpivirine dosing
25 mg daily with a meal, keep in original container
rilpivirine contraindications
all PPIs
rilpivirine side effects
CNS (depression, mood changes, suicidal ideation, insomnia)
NNRTI drug interactions
They are all 3A4 substrates and may also be an inducer, inhibitor, or both inducer and inhibitor (efavirenz)
Rilpivirine drug interactions
rilpivirine is a major substrate of 3A4, contraindicated with strong 3A4 inducers and PPIs
efavirenz drug interactions
methadone levels can be decreased by efavirenz. monitor for signs and symptoms of possible withdrawal

hormonal contraceptive levels may be decreased by efavirenz
Protease Inhibitors (PI) side effects
hyperglycemia, insulin resistance, lipohypertrophy (fat maldistribution), hyperlipidemia, hepatitis
Atazanavir class
PI
Reyataz generic
atazanavir
atazanavir dosing
300 mg + 100 mg ritonavir daily with food and water
atazanavir side effects
PR interval prolongation, indirect hyperbilirubinemia (leading to jaundic or scleral icterus-- think "bananavir", rash, nephrolithiasis
atazanavir notes
caution with acid-suppressive agents as they can reduce the absorption (and blood levels) of atazanavir
Darunavir class
PI
Prezista generic
darunavir
Darunavir dosing
tx naive: 800 mg + 100 mg ritonavir daily with food. swallow whole. must be given with ritonavir
darunavir warnings
caution in patients with sulfa allergy
darunavir side effects
nausea, diarrhea, rash (including SJS/TEN), increase LFTs, HA
Lopinvair + Ritonavir class
PIs
Kaletra generic
Lopinavir + Ritonavir
Lopinavir + ritonavir dosing
treatment naive: 800 mg lopinavir/200 mg ritonavir daily or 400/100 mg BID. take oral soln with food. tablets without regard to food.
Ritonavir class
PI
Norvir generic
ritonavir
ritonavir use
primarily used as booster agent and not as a sole PI
ritonavir dosing
100-400 mg daily-- booster dose, given in 1 or 2 divided doses with food

capsules: must be refrigerated; can be left at room temperature if used within 30 days

tablets store at room temp
ritonavir boxed warning
ritonavir may interact with many medications
ritonavir side effects
N/V/D, paresthesias, asthenia, altered taste, PR prolongation
Protease inhibitor drug interactions
ALL PIs are metabolized via CYP 450 and have many drug interactions. All PIs are 3A4 substrates and most are strong 3A4 inhibitors.

PIs can alter the INR (mainly decrease) in patients taking warfarin due to 2C9 induction; the INR should be closely monitored

PIs can incrase levels of PDE5 inhibitors and increase risk of toxicity
Ritonavir drug interaction
potent 3A4 inhibitor, used at low doses to increase or boost the level of other PIs

methadone levels may decrease. possible for methadone withdrawal

statins can increase PI levels. concurrent use of lovastatin and simvastatin with PIs is contraindicated
Dolutegravir class
INSTI
Tivicay generic
Dolutegravir
Dolutegravir side effects
insomnia, headache
Elvitegravir class
INSTI
Stribild renal adjustment
do not initiate if CrCl <70, discontinue when < 50
Stribild side effects
proteinuria
Raltegravir class
INSTI
Isentress generic
Raltegravir
Raletgravir dosing
400mg BID
Raltegravir side effects
insomnia, increase CPK, myopathy, rhabdo, rash (including SJS)
Stribild note
should not be combined with any other ART
Some common complications of ART
lactic acidosis and severe hepatomegaly with steatosis

immune reconstitution inflammatory syndrome: IRIS: a paradoxical worsening of a preexisting OI or malignancy when ART is initiated

Lipodistrophy

lipoatrophy

lipohypertrophy

diarrhea
pre-exposure prophylaxis
New HIV prevention method in which people who do not have HIV take emtricitabine/tenofovir (Truvada) 1 tab PO daily in combination with safe sex/behavior risk reduction practices
occupational postexposure prophylaxis recommendation
once blood is HIV confirmed, start therapy within 72 hours

three drug regimen: raltegravir + tenofovir/emtricitabine (Truvada) for 4 weeks
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