HIV

Terms in this set (91)

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)

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

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

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)

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

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

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.

Emtriva generic name

Emtricitabine class

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

1 tab daily without regards to food

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

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

tenofovir dosing

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

ALL NNRTIs can cause rash including SJS/TEN and hepatoxicity

Sustiva generic

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

Rilpivirine, RPV class

Edurant generic

rilpivirine dosing

25 mg daily with a meal, keep in original container

rilpivirine contraindications

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

Reyataz generic

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

Prezista generic

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

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

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

Tivicay generic

Dolutegravir side effects

insomnia, headache

Elvitegravir class

Stribild renal adjustment

do not initiate if CrCl <70, discontinue when < 50

Stribild side effects

Raltegravir class

Isentress generic

Raletgravir dosing

Raltegravir side effects

insomnia, increase CPK, myopathy, rhabdo, rash (including SJS)

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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