Lecture 6 (Antiretroviral agents)

Basic Viral Structure & Cellular TargetWhich of the following best describes the genomic nature of HIV and its primary cellular target? A) HIV is an RNA virus that primarily targets and destroys CD4+ T cells B) HIV is a double-stranded DNA virus that targets CD8+ cytotoxic T cells C) HIV is a single-stranded DNA virus that targets natural killer (NK) cells D) HIV is an RNA virus that targets mature erythrocytes and platelets

A) HIV is an RNA virus that primarily targets and destroys CD4+ T cells

Pathophysiology & Disease ProgressionProgressive depletion and loss of CD4+ T cells directly results in which clinical syndrome? A) Severe Combined Immunodeficiency (SCID) B) Acquired Immunodeficiency Syndrome (AIDS) C) Chronic Granulomatous Disease (CGD) D) Autoimmune Lymphoproliferative Syndrome (ALPS)

B) Acquired Immunodeficiency Syndrome (AIDS)

Epidemiologic Dominance of HIV TypesWhich HIV type accounts for the vast majority of cases worldwide? A) HIV-2 B) HIV-3 C) HIV-1 D) HIV-4

C) HIV-1

Geographical Localization of HIV-2Where is HIV-2 predominantly localized geographically? A) Eastern Europe B) North America C) East Asia D) Western Africa

D) Western Africa

Entry & Attachment Inhibitor ClassWhich of the following groups of agents belongs to the HIV entry and attachment inhibitor class? A) Maraviroc, Enfuvirtide, Ibalizumab, Fostemsavir B) Zidovudine, Lamivudine, Abacavir, Tenofovir C) Efavirenz, Nevirapine, Etravirine, Doravirine D) Raltegravir, Dolutegravir, Elvitegravir, Bictegravir

A) Maraviroc, Enfuvirtide, Ibalizumab, Fostemsavir

Capsid Inhibitor Drug TargetWhich agent functions specifically as a long-acting HIV capsid inhibitor targeting uncoating, assembly, budding, and release? A) Fostemsavir B) Lenacapavir C) Ibalizumab D) Maraviroc

B) Lenacapavir

Target Step of NRTIs and NNRTIsBoth NRTIs and NNRTIs inhibit which critical phase of the HIV life cycle? A) Cleavage of polyproteins into functional units B) Integration of viral DNA into the host genome C) Reverse transcription of viral RNA into DNA D) Viral attachment to the host CD4 receptor

C) Reverse transcription of viral RNA into DNA

Identification of NRTIsWhich collection of drugs represents Nucleoside/Nucleotide Reverse Transcriptase Inhibitors (NRTIs)? A) Efavirenz, Nevirapine, Etravirine, Delavirdine B) Ritonavir, Atazanavir, Darunavir, Fosamprenavir C) Raltegravir, Dolutegravir, Elvitegravir, Bictegravir D) Zidovudine, Lamivudine, Abacavir, Emtricitabine, Tenofovir

D) Zidovudine, Lamivudine, Abacavir, Emtricitabine, Tenofovir

Identification of NNRTIsWhich set of medications belongs to the Non-Nucleoside Reverse Transcriptase Inhibitor (NNRTI) drug class? A) Efavirenz, Nevirapine, Etravirine, Delavirdine, Doravirine, Rilpivirine B) Zidovudine, Lamivudine, Abacavir, Emtricitabine, Tenofovir C) Ritonavir, Atazanavir, Darunavir, Fosamprenavir, Lopinavir D) Raltegravir, Dolutegravir, Elvitegravir, Bictegravir, Cabotegravir

A) Efavirenz, Nevirapine, Etravirine, Delavirdine, Doravirine, Rilpivirine

Integrase Strand Transfer Inhibitors (INSTIs)What is the primary mechanism of Integrase Inhibitors (INSTIs)? A) Block cleavage of Gag/Gag-Pol polyproteins B) Prevent integration of viral DNA into the host genome C) Competitive inhibition of reverse transcriptase by chain termination D) Block interaction between gp120 and the host CCR5 co-receptor

B) Prevent integration of viral DNA into the host genome

Identification of INSTIsWhich group of agents belongs to the Integrase Inhibitor (INSTI) class? A) Ritonavir, Atazanavir, Darunavir, Saquinavir B) Zidovudine, Abacavir, Tenofovir, Emtricitabine C) Raltegravir, Dolutegravir, Elvitegravir, Bictegravir D) Efavirenz, Rilpivirine, Nevirapine, Doravirine

C) Raltegravir, Dolutegravir, Elvitegravir, Bictegravir

Mechanism of Protease Inhibitors (PIs)Protease inhibitors (PIs) exert their antiretroviral effect by: A) Preventing viral DNA insertion into human chromosomes B) Inhibiting the reverse transcription of RNA into DNA C) Blocking host cell entry after gp120 attachment D) Preventing the formation of mature, infectious virions

D) Preventing the formation of mature, infectious virions

Identification of Protease InhibitorsWhich collection of agents belongs to the Protease Inhibitor (PI) class? A) Ritonavir, Atazanavir, Darunavir, Fosamprenavir, Lopinavir, Tipranavir, Saquinavir B) Raltegravir, Dolutegravir, Elvitegravir, Bictegravir, Cabotegravir C) Efavirenz, Nevirapine, Etravirine, Delavirdine, Doravirine D) Maraviroc, Enfuvirtide, Ibalizumab, Fostemsavir, Lenacapavir

A) Ritonavir, Atazanavir, Darunavir, Fosamprenavir, Lopinavir, Tipranavir, Saquinavir

Un-targeted HIV Life Cycle StepsCurrently, there are NO approved antiretroviral drugs that target which processes of the HIV life cycle? A) Viral entry and membrane fusion B) Viral transcription or translation process C) Reverse transcription and integrase strand transfer D) Gag polyprotein cleavage and maturation

B) Viral transcription or translation process

Host Co-Receptor BiologyWhat role does CCR5 play during HIV infection? A) It is a viral capsid protein involved in uncoating B) It is an essential viral enzyme that cleaves polyproteins C) It is a host-cell co-receptor used by CCR5-tropic HIV-1 for viral entry D) It is a host nuclear transport protein that imports viral DNA

C) It is a host-cell co-receptor used by CCR5-tropic HIV-1 for viral entry

Maraviroc Mechanism of ActionHow does Maraviroc inhibit HIV entry into target host cells? A) Binds to the HR1 region of gp41 to block membrane hairpin formation B) Binds directly to Domain 2 of the CD4 receptor C) Inhibits viral gp120 synthesis in the cytoplasm D) Selective CCR5 antagonist that prevents interaction between gp120 and CCR5, preventing gp41-mediated fusion

D) Selective CCR5 antagonist that prevents interaction between gp120 and CCR5, preventing gp41-mediated fusion

Mandatory Pre-Treatment Assay for MaravirocWhich baseline laboratory test MUST be performed prior to initiating Maraviroc therapy? A) HIV tropism testing to ensure the presence of CCR5 co-receptors B) HLA-B*57:01 genetic screening C) Phenotypic reverse transcriptase assay D) Glucose-6-phosphate dehydrogenase (G6PD) screening

A) HIV tropism testing to ensure the presence of CCR5 co-receptors

Enfuvirtide Structure & FunctionWhat is the structural classification of Enfuvirtide? A) Recombinant humanized IgG1 monoclonal antibody B) Synthetic 36-amino-acid peptide that inhibits HIV membrane fusion C) Small-molecule nucleotide analogue D) Non-competitive allosteric inhibitor

B) Synthetic 36-amino-acid peptide that inhibits HIV membrane fusion

Enfuvirtide Binding TargetEnfuvirtide prevents HIV membrane fusion by binding to which specific region? A) Host CCR5 co-receptor binding pocket B) Domain 2 (D2) of host CD4 receptor C) HR1 region of gp41 D) Active site of HIV reverse transcriptase

C) HR1 region of gp41

Molecular Mimicry of EnfuvirtideAs a peptide drug, Enfuvirtide structurally mimics a portion of which natural viral sequence? A) Host CD4 domain 1 binding site B) Natural HIV-1 p24 capsid hexamer C) Natural gp120 V3 loop D) Natural gp41 HR2 sequence

D) Natural gp41 HR2 sequence

Fostemsavir BioactivationFostemsavir is classified as an oral prodrug that undergoes bioactivation into: A) Active drug temsavir B) Active metabolite carbovir C) Tenofovir diphosphate D) Emtricitabine triphosphate

A) Active drug temsavir

Temsavir Target & MechanismHow does active temsavir prevent HIV cell entry? A) Binds to host CCR5 to induce endocytosis B) Binds to viral gp120 and prevents gp120-mediated attachment to CD4 C) Binds to gp41 to arrest hairpin formation D) Inhibits host CD4 domain 2 displacement

B) Binds to viral gp120 and prevents gp120-mediated attachment to CD4

Ibalizumab Structural Classification & TargetIbalizumab is classified as a monoclonal antibody that binds directly to: A) Viral gp120 attachment site B) Viral gp41 HR1 domain C) Domain 2 (D2) of CD4 D) Host CCR5 receptor loop 2

C) Domain 2 (D2) of CD4

Ibalizumab Mechanism of ActionHow does Ibalizumab function as a post-attachment inhibitor? A) Prevents gp120 binding to CD4 entirely B) Cleaves CD4 receptors from host cell membranes C) Degrades viral gp41 upon contact D) Prevents conformational changes required for HIV entry after gp120 binds CD4

D) Prevents conformational changes required for HIV entry after gp120 binds CD4

NRTI Mechanism of ActionHow do Nucleoside/Nucleotide Reverse Transcriptase Inhibitors (NRTIs) inhibit viral replication? A) Compete with natural nucleotides for incorporation into viral DNA by reverse transcriptase (RT) B) Bind allosterically to a hydrophobic pocket adjacent to the RT active site C) Chelate divalent magnesium ions within the integrase catalytic site D) Competitive inhibition of viral protease cleavage

A) Compete with natural nucleotides for incorporation into viral DNA by reverse transcriptase (RT)

Critical Structural Feature of NRTIsWhat is the primary structural modification in NRTIs that prevents further DNA elongation? A) Addition of a bulky 2'-fluorine substitution B) Missing a 3'-OH group C) Absence of a nitrogenous purine or pyrimidine base D) Presence of a triple carbon-carbon bond at the 5' position

B) Missing a 3'-OH group

Ultimate Molecular Result of NRTI IncorporationWhen an NRTI is incorporated into the nascent viral DNA strand, it results in: A) Hypermutation of host cellular DNA B) Rapid degradation of host nuclear membrane C) DNA chain termination and cessation of HIV reverse transcription D) Allosteric inhibition of host RNA polymerase II

C) DNA chain termination and cessation of HIV reverse transcription

Zidovudine (AZT) Analogue ClassificationZidovudine (AZT) is a nucleoside analogue of which natural nucleoside? A) Guanosine B) Cytidine C) Adenosine D) Thymidine

D) Thymidine

Lamivudine & Emtricitabine ClassificationLamivudine (3TC) and Emtricitabine (FTC) are both structural analogues of: A) Cytidine B) Adenosine C) Thymidine D) Guanosine

A) Cytidine

Abacavir (ABC) Analogue ClassificationAbacavir (ABC) is classified as an analogue of which natural nucleoside? A) Thymidine B) Guanosine C) Cytidine D) Adenosine

B) Guanosine

Tenofovir Analogue ClassificationTenofovir is unique among standard NRTIs because it is an analogue of: A) Cytidine nucleotide B) Guanosine nucleoside C) Adenosine nucleotide D) Thymidine nucleoside

C) Adenosine nucleotide

Structural Distinction: Nucleosides vs. NucleotidesWhich structural feature is absent in nucleoside drugs (AZT, 3TC, FTC, ABC) compared to nucleotide analogues? A) Nitrogenous base ring B) Ribose sugar backbone C) 2' hydrogen atom D) Phosphate group in its structure

D) Phosphate group in its structure

Activation Requirement for Nucleoside AnalogsUnlike Tenofovir (a nucleotide analogue), nucleoside analogues require host cellular kinase activity to achieve which form? A) Active triphosphate forms B) Active monophosphate forms C) Unphosphorylated active state D) Active glucuronide conjugate

A) Active triphosphate forms

Zidovudine (AZT) Specific Active Triphosphate TargetThe active metabolite AZT-TP competes directly with which natural nucleotide substrate for reverse transcriptase incorporation? A) dCTP B) dGTP C) dATP D) dTTP

B) dGTP

Zidovudine (AZT) Adverse Effect ProfileWhich cluster of toxicities is specifically associated with Zidovudine (AZT) therapy? A) Bone marrow suppression, anemia, neutropenia, myopathy, and mitochondrial toxicity B) Severe hypersensitivity rash, Stevens-Johnson syndrome, and hepatotoxicity C) Nephrolithiasis, hyperbilirubinemia, and cardiac conduction delay D) Peripheral neuropathy, lipodystrophy, and CNS vivid dreams

A) Bone marrow suppression, anemia, neutropenia, myopathy, and mitochondrial toxicity

3TC & FTC Mechanism of ActionThe active metabolites 3TC-TP and FTC-TP compete with which natural nucleotide substrate during reverse transcription? A) dTTP B) dCTP C) dATP D) dGTP

B) dCTP

Structural Difference Between FTC and 3TCWhat structural modification distinguishes Emtricitabine (FTC) from Lamivudine (3TC)? A) Presence of an additional methyl group at position 5 B) Replacement of ribose with an acyclic chain C) Fluorine (F) substitution D) Addition of a sulfur atom in the oxathiolane ring

C) Fluorine (F) substitution

Shared Toxicities of Lamivudine & EmtricitabineWhich major class-related adverse effects are associated with both Lamivudine and Emtricitabine? A) Nephrolithiasis and bone mineral density loss B) Severe anemia and neutropenia C) Lactic acidosis and mitochondrial toxicity D) Neuropsychiatric reactions and insomnia

C) Lactic acidosis and mitochondrial toxicity

Dual Antiviral Activity of 3TC & FTCIn addition to HIV-1, both Lamivudine and Emtricitabine possess potent activity against which virus? A) Hepatitis C virus (HCV) B) Cytomegalovirus (CMV) C) Epstein-Barr virus (EBV) D) Hepatitis B virus (HBV)

D) Hepatitis B virus (HBV)

Resistance Mutation for 3TC & FTCWhich single amino acid substitution in HIV reverse transcriptase confers high-level cross-resistance to both 3TC and FTC? A) M184V B) K103N C) Y181C D) Q151M

A) M184V

Abacavir (ABC) Bioactivation PathAbacavir is converted intracellularly to carbovir, which is subsequently phosphorylated to which active competitor of natural dGTP? A) AZT-TP B) CBV-TP C) TFV-DP D) FTC-TP

B) CBV-TP

Abacavir (ABC) Hypersensitivity AssociationAbacavir hypersensitivity reaction (AHR) is strongly associated with which genetic biomarker? A) HLA-B57:02 B) HLA-B27:05 C) HLA-B57:01 D) HLA-A31:01

C) HLA-B*57:01

Mandatory Abacavir ScreeningWhich clinical requirement must be met before issuing a prescription for Abacavir? A) Tropism testing for CXCR4 co-receptor dominance B) Serum procalcitonin level check C) Baseline G6PD enzyme level assessment D) HLA-B*57:01 testing

D) HLA-B*57:01 testing

Formulations of Tenofovir ProdrugsTenofovir is commercially formulated into which two distinct prodrugs? A) TDF (tenofovir disoproxil fumarate) and TAF (tenofovir alafenamide) B) AZT and 3TC C) CBV and FTC D) ABC and d4T

A) TDF (tenofovir disoproxil fumarate) and TAF (tenofovir alafenamide)

Tenofovir Active Metabolite TargetThe active metabolite of Tenofovir (TFV-DP) competes with which natural nucleotide for incorporation into viral DNA? A) dCTP B) dATP C) dTTP D) dGTP

B) dATP

Toxicities of Tenofovir Disoproxil Fumarate (TDF)Which adverse effects are characteristic of TDF therapy due to higher systemic circulating tenofovir levels? A) Severe CNS disturbances and sleep impairment B) Hypersensitivity reactions and rash C) Renal toxicity and decreased bone mineral density D) Myelosuppression and severe anemia

C) Renal toxicity and decreased bone mineral density

Advantages of Tenofovir Alafenamide (TAF)Why does TAF demonstrate significantly lower renal and bone toxicity compared to TDF? A) TAF bypasses hepatic metabolism completely B) TAF does not undergo intracellular phosphorylation C) TAF acts as an NNRTI rather than an NRTI D) TAF delivers tenofovir more efficiently inside target cells

D) TAF delivers tenofovir more efficiently inside target cells

Genetic Barrier to Resistance of NNRTIsWhich statement accurately describes the resistance profile of the NNRTI class? A) NNRTIs generally have a high genetic barrier to resistance requiring multiple mutations B) NNRTIs generally have a low genetic barrier to resistance C) NNRTIs never develop resistance mutations in clinical practice D) NNRTI resistance requires simultaneous mutations in viral protease

B) NNRTIs generally have a low genetic barrier to resistance

Mechanism of NNRTI ResistanceHow do primary resistance mutations impact NNRTI efficacy? A) By causing hyper-phosphorylation of host kinases B) By completely preventing NRTI incorporation into viral DNA C) By altering the NNRTI-binding pocket of RT to reduce drug binding D) By blocking viral entry at the CD4 binding domain

C) By altering the NNRTI-binding pocket of RT to reduce drug binding

Primary NNRTI Resistance MutationsWhich pair of mutations in HIV reverse transcriptase confers significant resistance to first-generation NNRTIs? A) M184V and T215Y B) Q151M and K65R C) L90M and I50V D) K103N and Y181C

D) K103N and Y181C

Efavirenz Toxicity & Drug InteractionsWhich NNRTI is notable for causing prominent central nervous system (CNS) side effects and significant CYP450-mediated drug-drug interactions? A) Efavirenz B) Doravirine C) Rilpivirine D) Nevirapine

A) Efavirenz

INSTI Class NomenclatureAntiretroviral medications belonging to the Integrase Inhibitor (INSTI) class can be recognized by which common suffix? A) -navir B) -gravir C) -virine D) -citabine

B) -gravir

INSTI Mechanism of Action at the Molecular LevelIntegrase inhibitors block HIV integration into host chromosomes by binding the integrase active site and interacting with which essential divalent ions? A) $Fe^{2+}$ ions B) $Zn^{2+}$ ions C) $Mg^{2+}$ ions D) $Ca^{2+}$ ions

C) $Mg^{2+}$ ions

Structural Motif in INSTIsINSTI molecules specifically possess functional groups designed to interact with metal ions by coordinating: A) $Fe^{3+}$ ions required for reverse transcription B) $Cu^{2+}$ ions required for capsid uncoating C) $Zn^{2+}$ ions required for protease dimer cleavage D) $Mg^{2+}$ ions required for integrase activity

D) $Mg^{2+}$ ions required for integrase activity

Role of HIV Protease in Viral Life CycleWhy is HIV protease essential for the viral replication cycle? A) It synthesizes viral RNA from host DNA templates B) It translocates viral DNA into the host nucleus C) It is essential for the maturation of newly formed HIV virions D) It attaches viral particles to host CD4 receptors

C) It is essential for the maturation of newly formed HIV virions

HIV Maturation SequenceWhat is the correct sequence of steps involved in HIV maturation? A) Viral budding $\rightarrow$ Gag/Gag-Pol polyproteins $\rightarrow$ HIV protease cleavage $\rightarrow$ Functional viral proteins $\rightarrow$ Mature infectious HIV B) HIV protease cleavage $\rightarrow$ Viral budding $\rightarrow$ Strand transfer $\rightarrow$ Mature infectious HIV C) Gag/Gag-Pol cleavage $\rightarrow$ Attachment $\rightarrow$ Membrane fusion $\rightarrow$ Mature infectious HIV D) Integration $\rightarrow$ Viral budding $\rightarrow$ Transcription $\rightarrow$ Mature infectious HIV

A) Viral budding $\rightarrow$ Gag/Gag-Pol polyproteins $\rightarrow$ HIV protease cleavage $\rightarrow$ Functional viral proteins $\rightarrow$ Mature infectious HIV

Consequence of Protease Inhibitor ActionInhibition of HIV protease by PIs blocks Gag/Gag-Pol polyprotein cleavage, directly producing: A) Hyperactive, rapidly replicating viral clones B) Immature, noninfectious virions C) Completely unencapsulated naked viral RNA D) Host cell apoptosis without viral particle release

B) Immature, noninfectious virions

Protease Inhibitor Side Effect ProfileWhich cluster of adverse events is commonly associated with Protease Inhibitor (PI) therapy? A) Bone marrow suppression, anemia, and myopathy B) Peripheral neuropathy, QTc prolongation, and tendinopathy C) CNS vivid dreams, dizziness, and hallucinations D) GI effects, hepatotoxicity, and dyslipidemia

D) GI effects, hepatotoxicity, and dyslipidemia