iPTX3 exam 4 - Med Chem AVx HIV (Cao)

What is the major coreceptor for macrophage-tropic strains?

CCR5

T or F:

HIV is a retrovirus that has double strain RNA

True

What immune cell(s) does HIV infect and affect?

CD4+, macrophages

What enzymes does HIV use in DNA replication?

Reverse transcriptase; RNA dependent DNA polymerase

What is the major coreceptor for T-cell-tropic strains?

CXCR4

How is CXCR4 involved in with the progression of HIV?

It progresses from HIV to AIDS

How is CCR5 involved with the infectivity of HIV?

It is involved with the transmission of infection

What are the 4 categories of AVx that are used for HIV treatment?

Reverse transcriptase inhibitors, Viral maturation inhibitors, Integration, Transcription, and Translation inhibitors, Entry inhibitors

The two strategies that are used to block the CCR5 receptors are what?

Non-agonistic ligands, monoclonal antibodies

What is an alternative route in which we can reduce CCR5 cell surface expression on HIV cells?

Using siRNA or intrakine

What is the primary receptor on human cells that HIV enters through?

CD4

What is the secondary receptors on human cells that HIV enters through?

Chemokine receptors

What receptor on macrophages does HIV use to enter it?

CCR5

what receptor on CD4+ cell (T-cells) does HIV use to enter it?

CXCR4

what kind of treatment do we do to treat Acute Primary HIV infections?

Combo antiretroviral (ARVx) therapy to suppress virual replication to levels below the detection of plasma HIV RNA assays

T or F:

Patients who are taking effective treatment for HIV are not considered infectious, but they should be counseled to abstain

False

What is a Long-term nonprogressor HIV patient?

Infected by HIV for over 10 years and never converted into AIDS

What is the CD4 cell count that determines that a patient should receive treatment and it is recommended?

< 350 cells/mm^3

What CD4 cell count is treatment recommended for asymptomatic HIV patients?

350 - 500 cells/mm^3

What are the 5 ARVx drugs that are used for HIV?

Nucleoside (NRTIs) or Nucleotide (NtRTIs) reverse transcriptase inhibitors, Non-nucleoside reverse transcriptase inhibitors (NNRTIs), Protease inhibitors (PIs), Integrase inhibitors, Fusion/Entry inhibitors

T or F:

NRTIs or NtRTIs are purine or pyramidine based nucleoside or nucleotides

True

What do NRTIs act as that allows substrate binding to happen on the site of RT?

Chain terminators or inhibitors

What does NTRIs transform into to be active?

5'-triphosphate form

T or F:

NRTIs need to be hydrolyzed in order otherwise be active in the body

False

How are NtRTIs different from NRTIs?

NtRIs already contain a phosphate group and the under go 2 steps to become active

What enzyme does NRTIs and NtRIs compete aganist in the HIV cell?

2'-deoxynucleotide

what are the 6 kinds of NtRTI drugs?

Cytosine analogs, adenosine/guanosine analogs, thymidine analogs,

What are the examples of a cytosine analogs?

Emtricitabine, Lamivudine

What are the examples of an adenosine/guanosine analogs?

Abacavir sulfate (ABC), didanosine (ddI)

What are the examples of thymidine analogs?

Stavudine (d4T), zidovudine (ZDV)

Tenofovir disoproxil nucleotide is an examples of what?

adenosine-derived nucleotide reverse transcriptase inhibitor

What is the MoA of NNRTIs?

Inhibit viral DNA replications by binding to reverse transcriptase (RT)

How do NNRTIs bind to RT?

Allosterically

T or F:

NNRTIs require bioactivation by kinases

False

Nevirapine, delavirdine, efavirenz, etravirine, and rilpivirine are examples of what?

NNRTIs

What is needed in the process of the replication cycle of HIV that protease inhibitors prevent from being processed?

GAG and POL polyproteins

drugs that have the -navir suffix, are what category of ARVx?

Protease inhibitors

drugs that have the -tegravir suffix are what category of ARVx?

Integrase inhibitors

What is the MoA of integrase inhibitors (INSTI)?

Prevents the binding of the pre-integration complex to host cell DNA, which stops the integration step of HIV replication

what is the MoA of Enfuvirtide?

biomimetic peptide that binds to gp41 and prevent viral fusion with the host cell membrane

what is the MoA of Miraviroc?

competes for binding of HIV to CCR5 co-receptor

Miraviroc is an example of what category of ARVx?

Viral coreceptor antagonist

What are the advantages of combination therapy?

Less drug resistance, reducing indiviudal drug toxicity, multiple receptor targets

What is the benefit of using combination therapy in ARVx for HIV treatment?

Favorable synergistic properties that allows a decrease in dose or dosing frequency

What is the typical recommended ARVx regimen?

2 NRTIs + 1 PI

2 NRTIs + 1 NNRTI

2 NRTIs + 2 PIs

T or F:

Generally, NRTIs of the same nucleobase should not be co-administered

True

T or F:

Using two adenosine analogs are less effective together compared to other recommended NRTI treatment regimens

True

T or F:

Coadministration of didanosine and tenofovir is recommended for initial therapy

False

What are the 3 ways in which active immunotherapy works?

Protein/peptide, DNA vaccine, viral vector vaccine

What are the 3 ways in which passive immunotherapy (antibodies)?

Monoclonal, polyclonal antibody, modified antibodies

What are preventative vaccines used for?

Higher and longer antibody response; used in patients who has tolerance to the vaccine-induced T-cell response

what is the physiology behind HIV making patients become immunocompromised?

CD4+ T-cell depletion impairs the immune system and allows opportunistic infections (OIs) to occur

What is the most common bacterial OIs?

Tuberculosis (TB)

What are the most common viral OIs?

Cytomegalovirus, HCV, Herpes simplex virus, HPV

what is the most common fungal OIs?

Pneumocystitis Pneumonia (PCP)

What is the most common Protozoal OIs?

Toxoplasmosis

What is the CD4+ cell count in which PCP occurs in HIV patients?

< 200 cells/mm^3

What is the preferred ABx to treat PCP in HIV patients?

Bactrim

T or F:

Patients with mod-to-severe PCP should be treated with corticosteroids ASAP

True

What are the alternative steroid regimens for HIV patients?

Pentamidine, Dapsone

What are the first-line medications for Toxoplasmosis?

Pyrimethamine + Sulfadiazine + Leucovorin

A CD4+ cell count of 200 cells/mm^3 indicates what OI?

PCP

A CD4+ cell count of 100 cells/mm^3 indicates what OI(s)?

Toxoplasmosis, Cryptococcal infections

A CD4+ cell count of 50 cells/mm^3 indicates what OI?

CMV infections

What is the induction therapy regimen for Cryptococcal meningitis?

AmpB + Flucytosine x2 weeks

What is the first-line medication regimen for Cytomegalovirus (CMV)?

Gancliclovir, Valganciclovir

When would patients receive life long prophylaxis for Mycobacterium avium complex (MAC)

Having HIV and CD4+ cell count of < 50 cells/mm^3

What is the preferred AVx therapy for MAC?

Rifabutin

What is the preferred ABx therapy for MAX?

Clarithomycin OR azithromycin + a second ABx

Isoniazid and Pyrazinamide are not effective against what OI?

MAC infections