Pharmacology Exam 5

There are -1.2 million people infected with

human immunodeficiency virus (HIV) in the U.S., and -13% of those are unaware that they are infected.

Annually, how many people are newly diagnosed with HIV

38,000 people

If left untreated, HIV can progress to an advanced and severe stage of infection called

acquired immunodeficiency syndrome (AIDS).

When HIV continues to replicate, what happens to the viral load and CD4

viral load increases and CD4 count decreases 

when is AIDS diagnosed

CD4 count falls below 200 cells/mm^ or the patient develops an AIDS-defining condition.

how is infection of HIV spread

direct contact with blood, semen, vaginal secretions or rectal secretions, or ingestion of breast milk.

what are most infection of HIV caused by 

unprotected vaginal or rectal sex, and sharing injection drug equipment, including needles.

can HIV be spread from mom to baby and during what

yes and pregnancy, childbirth, or breastfeeding.

what is the mom giving baby HIV called

mother- to-child or vertical transmission.

what doese CDC recommend for screening of HIV

at least once for all patients who are 13 - 64 years old.

what does screening of high risk individuals look like 

testing should be done at least annually

The high-risk indicators for becoming infected with HIV are:

Sharing drug-injection equipment: needles, syringes and cookers (used to mix up or "cook" drugs)

High-risk sexual behaviors:

men who have sex with men, sex with multiple partners, sex with a person known to be infected with HIV, sexual activity resulting in a history of sexually transmitted infections (e.g., syphilis, chlamydia, gonorrhea).

what is another high-risk indicator for becoming infected with HIV

A history of hepatitis or tuberculosis (TB) infection.

what antibodies does the initial screening indicate

tests for p24 antigens and HIV-1/HIV-2 antibodies

What does the confirmatory HIv testing look for 

antibody differentiation immunoassay

what are the intermediate and negative confirmatory test indicate

HIV-1 Nucleic acid Test, quantifies viral load

what does a postive confirmatory test mean

HIV diagnosis and subtype confirmed

epidemiology of acute HIV infection

typically presents 2-4 weeks after exposure

clinical features of acute HIV

mononucleosis-like syndrome (fever, lymphadenopathy, sore throat, arthralgis)

generalized macular rash 

gastrointestinal symptoms

diagnosis of acute HIV

viral load is markedly elevated

HIV antibody testing is negative

CD4 count may be normal

management of acute HIV

combination antiretroviral therapy

partner notification, consider secondary prophylaxis

risks factors of pnemocystis jirovecii

CD4+ count<200 cells

oropharyngeal candidiasis 

prophylaxis of pnemocystis jirovecii

trimethoprim-sulfamethoxazole 

risks factors of toxoplasma gondiii

CD4+ count<100 cells

positive toxoplasma IgG antibody

prophylaxis of toxoplasma gondii

trimethoprim-sulfamethoxazole 

risk factors of myobacterium avium complex

CD4+ count< 50 cells

prohylaxis of Mycobacterium avium

azithromycin

risk factor of histoplasma capsulatum 

CD4+ count< 150 cells 

Endemic area (Ohio and Mississippi River Valley) 

prophylaxis of histoplasma capsulatum

Itraconazole

Symptomatic primary HIV infection approximately 2 to 4 weeks after infection

Flu-like viral syndrome develops with fever, lymphadenopathy, pharyngitis, rash, and myalgias

Asymptomatic infection

No abnormal physical findings

Symptomatic HIV infection

Development of common infections

Advanced HIV disease/AIDS

Severe immunosuppression, CD4 T lymphocytes (CD4 cells) count less than 200 cells/mm³

Predictors for successful treatment with antiretroviral therapy (ART) in HIV-positive patients include:

The patient is strictly adherent to the ART treatment regimen

when should one start antiretroviral thearpy 

soon as possible in all HIV infected individuals 

what is the goal of ART

to reduce disease progression by suppressing the HIV viral load, preserving the immune system and reducing HIV-associated morbidity and mortality.

treatment adherence is essentail for what 

to prevent drug resistance.

what is the goals of treatment

1.Achieve maximal suppression of plasma viral load for as long as possible.

2.Delay the development of  medication resistance.

3.Preserve CD4 T-cell numbers.

4.Confer substantial clinical benefits, leading to reduction in morbidity and mortality.

a challenge faced with ART is

drug-resistant mutations of HIV

how many US food and Drug Administrations approved ART

20 

what is going on with the treatment of HIV disease

dynamic, rapidly changing arenadynamic, rapidly changing area

HIV medications are always used in

combination to reduce the amount of HIV in the blood.

Ongoing HIV replication leads to immune system damage and progression to AIDS.

Plasma HIV ribonucleic acid (RNA) and CD4 T-cell levels must be regularly measured (every 3 to 6 months).

how should treatment decsions be made

should be individualized based on the risk of disease progression as indicated by plasma HIV RNA levels and CD4 measurements.

what is the goal of therapy 

the maximum achievable suppression of  HIV replication.

what is the most effective way to achieve sustained suppression of HIV replication

combination of effective anti-HIV medications.

ART should be initiated in patients with

AIDS-defining illness or CD4 count less than 200 cells/mm³

HIV-associated nephropathy

Co-infection with hepatitis B infection

Pregnant women

Patients with CD4 counts <500 cells/mm³

potential benefits of early intervention sould be what?

weighed against the risks of early therapy.

ART regimen is determined by

Comorbid conditions

Convenience

Gender and pretreatment CD4 T-cell count (nevirapine)

Genotypic drug resistance testing

HLA B*5701 testing if considering abacavir

Patient adherence potential

Potential adverse drug effects

Potential drug interactions with other medications

Pregnancy potential

nucleoside reverse what

transcriptase inhibitors

Nonnucleoside reverse

transcriptase inhibitors

the four other families of HIV antiretroviral drugs

Protease inhibitors

Fusion inhibitors

Integrase strand transfer inhibitor

CCR5 antagonists

Nucleoside/Nucleotide Reverse Transcriptase Inhibitors (NRTIs)

Abacavir (Ziagen)
Emtricitabine (Emtriva)
Lamivudine (EpMr)
Tenofovir disoproxil fumarate, TDF (Viread)

Zidovudine (Retrovir)

What are the no longer recommended Nucleoside/Nucleotide Reverse Transcriptase Inhibitors (NRTIs)

Didanosine
Stavudine

Mechanism of action for Nucleoside/Nucleotide Reverse Transcriptase Inhibitors (NRTIs)

Competitively inhibit nucleotide binding to reverse transcriptase and terminate the DNA chain (lack a 3′ OH group).

All need to be phosphorylated to be active.

Tenofovir is a what

nucleotide

what can ZVD be used for

for general prophylaxis and during pregnancy to decrease risk of fetal transmission.

side effects of Nucleoside/Nucleotide Reverse Transcriptase Inhibitors (NRTIs)

myelosuppression

nephrotoxicity

Myelosuppression

can be reversed with granulocyte colony-stimulating factor [G-CSF] and erythropoietin

how can abacavir contraindication occur

patient has HLA-B*5701 mutation due to increase risk of hypersensitivity.

Non-Nucleoslde Reverse Transcriptase Inhibitors (NNRTIs)

Efavirenz (SustiVa)

Rilpivirine (Edurant)

Doravirine (Pifeltro)

Etravirine (Intelence)

Nevirapine (Viramune XR)

no longer recommended Non-Nucleoside Reverse Transcriptase Inhibitors (NNRTIs)

Delavirdine 

Mechanism of action of Non-Nucleoside Reverse Transcriptase Inhibitors (NNRTIs)

Non-competitively inhibit the reverse transcriptase enzyme, preventing the conversion of HIV RNA to HIV DNA in stage 3 (reverse transcription) of the HIV life cycle.

Side effects of Non-Nucleoside Reverse Transcriptase Inhibitors (NNRTIs)

Rash and hepatotoxicity are common to all NNRTIs.

whart are side effects of efavirenz

vivid dreams and CNS symptoms 

what does Rilpivirine need for absorption

acidic gut

what do not use Rilpivirine with

PPIs

if taking H2RAs, how does that work when also taking Rilpivirine

Take H2RAs at least 12 hours before or 4 hours after rilpivirine

when to take antacid when also taking rilpivirine

take antacids at least 2 hours before or 4 hours after rilpivirine

Integrase strand transfer inhibitors

Bictegravir

Dolutegravir

mechanisms of action for Integrase strand transfer inhibitors

Inhibit HIV genome integration into host cell chromosome by reversibly inhibiting HIV integrase.

side effects of Integrase strand transfer inhibitors

Increases creatine kinase

Weight gain

What are integrase strand transfer inhibitors also called

integrase inhibitors 

Protease Inhibitors (Pis)

Atazanavir (Reyataz)

Darunavir (Prezista)

Fosamprenavir (Lexiva)

Lopinavir / ritonavir. LPV/r (Kaletra)’

Saquinavir (Invirase)

Tipranavir (Aptivus)

no longer reccomended Protease Inhibitors (Pis)

Indinavir

Nelfinavir

mechanism of action for Protease Inhibitors (Pis)

•Prevents maturation of new virions.

•Maturation depends on HIV-1 protease (pol gene), which cleaves the polypeptide products of HIV mRNA into their functional parts.

•Thus, protease inhibitors prevent maturation of new viruses.

side effects of Protease Inhibitors (Pis)

•Hyperglycemia

•GI intolerance (nausea, diarrhea)

all protease inhibitors require boosting with

ritonavir or cobicistat.

side effects of the protease inhibitor Rifampin

(potent CYP/UGT inducer) decreases protease inhibitor concentrations

what to use instead of rifampin

rifabutin

side effects of the protease inhibitor ritonavir

cytochrome P-450 inhibitor) is only used as a boosting age

Protease inhibitors on metabolic syndrome

decrease HDL

increase LDL and TG

Increase blood glucose

insulin resistance

abdominal adiposity

Entry and Attachment inhibitors

Enfuvirtide (fuzeon)

Maraviroc (Selzentry)

Enfuvirtide

fusion inhibitor

Maraviroc

CCRS antagonist

mechanism of action of enfuvirtide

Binds gp41, inhibiting viral entry.

Enfuvirtide inhibits fusion.

side effects of Enfuvirtide

•Risk of bacterial pneumonia

•Hypersensitivity reactions

•Local injection site reactions (occur in nearly all patients)

Pain, erythema, nodules and cysts, ecchymosis, nausea, diarrhea and fatigue

mechanisms of action of maraviroc

Binds CCR-5 on surface of T cells/monocytes, inhibiting interaction with gp120.

Maraviroc inhibits docking.

side effects of Maraviroc

•Hepatotoxicity (boxed warning)

•Hypersensitivity reactions

•CV events (including Ml)

•Orthostatic hypotension in patients with renal impairment

medication resistence is due to

Poor patient adherence to the ART regimen

Drug–drug or drug–food interactions

Abnormal absorption, distribution, metabolism, or excretion of the medicine

what is the first sign HIV resistance?

detectable plasma viral RNA levels.

what are phenotype assays used for

to measure sensitivity to various antiretroviral agents.

what is ART failure defines as 

the failure to achieve or maintain suppression of viral replication to less than 50 copies/mL

what are the causes of ART failure

Suboptimal adherence

Toxicity

Patient factors that contribute to antiretroviral therapy (ART) failure include ART adverse effects

Discontinuation or interruption of ART is associated with

HIV viral rebound, immune decompensation, and clinical progression.

Interruption of ART may become necessary if

Concurrent illness

Severe drug toxicity

Surgery that precludes oral therapy

Antiretroviral medication nonavailability

Patients who are taking antiretroviral therapy need to have the following monitored:

uAdherence to medications and medical visits

uAffective mental health problems

uAlterations in metabolism of lipids and glucose

uCardiovascular risk

uHepatitis B and C co-infection

uHigh-risk behaviors

uImmunization status

uRenal and hepatic function

uSexually transmitted infections

uSomatic signs and symptoms

uTobacco, alcohol, and substance use

Outcome Evaluation of ART and HIV therapy

Treatment plans are individualized to each patient.

Success is determined by when the patient begins therapy and how well he or she is able to adhere to therapy.

Types of headaches 

migraine, hypertension, stress