Drug Classification · Questions 1–6
Identify the pharmacological class or categorical label for each drug or receptor. Vocabulary preparation is sufficient to answer every question in this section.
Question 1
Which of the following antiretroviral drugs is classified as a protease inhibitor?
Correct Answer
B — Darunavir
Rationale
Darunavir is a protease inhibitor. Dolutegravir is a second-generation integrase strand transfer inhibitor. Maraviroc is a CCR5 antagonist and entry inhibitor. Rilpivirine is a second-generation non-nucleoside reverse transcriptase inhibitor.
Question 2
Which of the following drugs is classified as a pharmacokinetic booster rather than an active antiretroviral agent when used at low doses in combination regimens?
Correct Answer
D — Ritonavir
Rationale
Ritonavir at low boosting doses (100 to 200 mg) is classified as a pharmacokinetic booster. At these doses it provides no meaningful antiviral activity and is used solely to inhibit cytochrome P450 3A4 and P-glycoprotein, raising concentrations of co-administered protease inhibitors. Darunavir is the active protease inhibitor it most commonly boosts. Dolutegravir is an integrase strand transfer inhibitor requiring no booster. Enfuvirtide is a fusion inhibitor.
Question 3
Which of the following drugs is classified as a second-generation integrase strand transfer inhibitor?
Correct Answer
A — Dolutegravir
Rationale
Dolutegravir is a second-generation integrase strand transfer inhibitor, along with bictegravir and cabotegravir. Raltegravir and elvitegravir are first-generation integrase strand transfer inhibitors with lower genetic resistance barriers. Maraviroc is a CCR5 antagonist and entry inhibitor, not an integrase inhibitor.
Question 4
Which of the following drugs is classified as a first-generation integrase strand transfer inhibitor?
Correct Answer
C — Raltegravir
Rationale
Raltegravir is a first-generation integrase strand transfer inhibitor, along with elvitegravir. Dolutegravir, bictegravir, and cabotegravir are all classified as second-generation integrase strand transfer inhibitors with substantially higher genetic resistance barriers than the first-generation agents.
Question 5
Which of the following antiretroviral drugs is classified as a CCR5 antagonist?
Correct Answer
A — Maraviroc
Rationale
Maraviroc is classified as a CCR5 antagonist and entry inhibitor. Enfuvirtide is a fusion inhibitor that blocks gp41-mediated membrane fusion. Fostemsavir is an attachment inhibitor that binds gp120 directly. Ibalizumab is a monoclonal antibody that blocks HIV entry by targeting the CD4 receptor without impairing immune function.
Question 6
Which of the following drugs is classified as a pharmacokinetic booster that has no intrinsic antiviral activity against HIV?
Correct Answer
C — Cobicistat
Rationale
Cobicistat is classified as a pharmacokinetic booster developed specifically to inhibit cytochrome P450 3A4 and P-glycoprotein; it has no intrinsic antiviral activity against HIV. Atazanavir, darunavir, and lopinavir are all active protease inhibitors that target the HIV aspartyl protease.
Core Pharmacology · Questions 7–14
Apply your understanding of drug mechanisms, pharmacokinetics, and adverse effects. Each question requires one reasoning step.
Question 7
Integrase strand transfer inhibitors block HIV integration into host chromosomal deoxyribonucleic acid. Which of the following best explains the molecular mechanism by which these drugs achieve this effect?
Correct Answer
B — They chelate two magnesium ions in the integrase active site, specifically blocking the strand transfer step while leaving the prior 3′-processing step unaffected
Rationale
HIV integrase performs two sequential reactions: 3′-processing in the cytoplasm and strand transfer in the nucleus. Integrase strand transfer inhibitors contain a diketo acid pharmacophore that chelates two magnesium ions in the integrase active site. This chelation specifically blocks the strand transfer step — insertion of viral deoxyribonucleic acid into the host chromosome — while 3′-processing proceeds normally. The mechanism is not allosteric, not covalent, and does not involve competition with host chromosomal deoxyribonucleic acid.
Question 8
A patient with HIV infection is stable on a boosted protease inhibitor regimen and develops hypercholesterolemia. The prescriber considers adding a statin. Which of the following best explains why simvastatin and lovastatin are absolutely contraindicated in this patient?
Correct Answer
D — The pharmacokinetic booster inhibits CYP3A4, raising simvastatin and lovastatin plasma concentrations up to 50-fold and producing a high risk of rhabdomyolysis
Rationale
Simvastatin and lovastatin are extensively metabolized by CYP3A4. Pharmacokinetic boosters — ritonavir and cobicistat — are potent CYP3A4 inhibitors. Co-administration raises simvastatin and lovastatin plasma concentrations up to 50-fold, dramatically increasing the risk of myopathy and rhabdomyolysis. These statins are absolutely contraindicated with boosted protease inhibitor regimens. Pravastatin, rosuvastatin, and pitavastatin are preferred alternatives because they are not extensively metabolized by CYP3A4 and are less affected by booster-mediated inhibition.
Question 9
A patient starting dolutegravir is noted to have a rise in serum creatinine of 0.1 to 0.2 mg/dL within the first four weeks of therapy. Repeat testing confirms the elevation is stable and the patient has no symptoms or signs of kidney disease. Which of the following best explains this laboratory finding?
Correct Answer
A — Dolutegravir inhibits renal tubular secretion of creatinine, raising serum creatinine without reducing true glomerular filtration rate
Rationale
Dolutegravir inhibits the renal tubular transporter responsible for creatinine secretion, producing a modest rise in serum creatinine that does not reflect a reduction in true glomerular filtration rate. This is the same mechanism as cobicistat-mediated creatinine elevation. The effect is predictable, benign, and stabilizes within the first four weeks. Cystatin C-based estimates of glomerular filtration rate, which are unaffected by tubular secretion, remain stable and confirm that true kidney function is preserved. The other options describe mechanisms that would represent genuine renal injury, which this finding does not.
Question 10
Antacids containing magnesium or aluminum, calcium supplements, and iron supplements substantially reduce the absorption of integrase strand transfer inhibitors when taken at the same time. Which of the following best explains this interaction?
Correct Answer
C — The diketo acid pharmacophore of integrase strand transfer inhibitors chelates divalent and trivalent cations in the gastrointestinal tract, forming insoluble complexes that are not absorbed
Rationale
The same diketo acid pharmacophore that chelates magnesium ions in the integrase active site also chelates dietary and supplemental divalent cations (calcium, magnesium, iron) and trivalent cations (aluminum) in the gastrointestinal tract. The resulting insoluble drug-cation complexes cannot be absorbed, dramatically reducing integrase strand transfer inhibitor bioavailability. This is not a pH-dependent, P-glycoprotein-mediated, or transporter-competitive interaction. For dolutegravir and raltegravir, cation-containing products must be separated from dosing by at least two hours before or six hours after.
Question 11
Rifampin reduces dolutegravir plasma exposure by approximately 54 percent when the two drugs are co-administered. Which of the following best explains the mechanism of this interaction and the approved compensatory strategy?
Correct Answer
B — Rifampin induces UGT1A1 and CYP3A4, accelerating dolutegravir metabolism; the approved strategy is to double the dolutegravir dose to 50 mg twice daily
Rationale
Rifampin is a potent inducer of UGT1A1 and CYP3A4, both of which are involved in dolutegravir metabolism. Induction accelerates dolutegravir clearance, reducing plasma exposure by approximately 54 percent. The approved compensatory strategy is to double the dolutegravir dose from 50 mg once daily to 50 mg twice daily, which restores adequate plasma concentrations. Bictegravir is not an appropriate alternative because rifampin reduces bictegravir exposure by approximately 75 percent and dose doubling within the fixed-dose combination has not been validated, making bictegravir contraindicated with rifampin.
Question 12
A physician considers adding maraviroc to the regimen of a patient with treatment-experienced HIV infection. Before prescribing maraviroc, the physician must order a co-receptor tropism assay. Which of the following best explains why this testing is required?
Correct Answer
D — Maraviroc is only active against CCR5-tropic virus; if the patient harbors CXCR4-tropic or dual-tropic virus, maraviroc will fail to suppress replication
Rationale
Maraviroc blocks the CCR5 co-receptor, preventing CCR5-tropic (R5-tropic) HIV from completing membrane fusion. HIV uses either CCR5 or CXCR4 as a co-receptor, and some patients harbor CXCR4-tropic or dual/mixed-tropic virus — particularly those with advanced disease. Because maraviroc has no activity against CXCR4-tropic virus, prescribing it without confirming CCR5 tropism risks complete treatment failure. Co-receptor tropism assays confirm R5 tropism before maraviroc is used. The other options describe conditions that do not apply to maraviroc prescribing requirements.
Question 13
Protease inhibitors allow HIV virions to bud from infected cells but render those virions non-infectious. Which of the following best explains why virions produced in the presence of a protease inhibitor cannot establish new infections?
Correct Answer
A — HIV protease cleaves the Gag and Gag-Pol polyproteins after budding; without this cleavage, structural and enzymatic proteins remain immature and the virion cannot replicate
Rationale
HIV protease is an aspartyl protease that cleaves the Gag and Gag-Pol polyproteins into mature structural proteins (capsid, matrix, nucleocapsid) and functional enzymes (reverse transcriptase, integrase, protease itself) after virion budding. When a protease inhibitor blocks this cleavage, the polyproteins remain intact and the virion is morphologically immature. These immature particles can bud and are released but cannot establish productive infection in new cells. This is a mechanistic distinction from reverse transcriptase and integrase inhibitors, which block earlier steps and prevent proviral formation. Options B, C, and D describe mechanisms that do not reflect protease inhibitor pharmacology.
Question 14
Patients switching to integrase strand transfer inhibitor-based antiretroviral regimens frequently gain weight, with greater weight gain observed when the integrase strand transfer inhibitor is combined with tenofovir alafenamide rather than tenofovir disoproxil fumarate. Which of the following best explains the greater weight gain seen with the tenofovir alafenamide combination?
Correct Answer
C — Tenofovir disoproxil fumarate suppresses appetite through off-target effects; switching to tenofovir alafenamide removes this suppression, contributing to greater weight gain
Rationale
Weight gain on integrase strand transfer inhibitor-based regimens reflects a combination of factors: immune reconstitution effects as health returns, direct metabolic effects of integrase inhibition, and removal of tenofovir disoproxil fumarate-mediated appetite suppression. Tenofovir disoproxil fumarate appears to have off-target effects that modestly suppress appetite and body weight; tenofovir alafenamide, with its far lower systemic tenofovir exposure, does not produce this suppression. The result is greater weight gain when integrase strand transfer inhibitors are combined with tenofovir alafenamide versus tenofovir disoproxil fumarate. Options A, B, and D describe mechanisms not supported by current evidence for either tenofovir formulation.
Clinical Correlations · Questions 15–18
Apply pharmacological knowledge to clinical scenarios. Each vignette presents a patient situation; the question tests mechanism of action or drug selection.
Question 15
A 38-year-old woman with HIV infection is virologically suppressed on a dolutegravir-based antiretroviral regimen. Her physician recommends she begin a calcium supplement for bone health. The pharmacist advises her not to take the calcium supplement at the same time as her dolutegravir. Which of the following best explains why timing separation is required?
Correct Answer
D — The diketo acid pharmacophore of dolutegravir chelates calcium ions in the gastrointestinal tract, forming an insoluble complex that cannot be absorbed
Rationale
Dolutegravir contains a diketo acid pharmacophore that chelates the two magnesium ions in the integrase active site — the same chemical group also chelates divalent cations such as calcium in the gastrointestinal tract. When dolutegravir and calcium are taken together, chelation forms an insoluble drug-calcium complex that is not absorbed, substantially reducing dolutegravir bioavailability and risking virologic failure. Calcium supplements, antacids containing magnesium or aluminum, and iron supplements must all be separated from dolutegravir dosing by at least two hours before or six hours after. Options A, B, and C describe mechanisms that do not apply to this interaction.
Question 16
A 41-year-old man with HIV infection is virologically suppressed on dolutegravir 50 mg once daily. He is newly diagnosed with pulmonary tuberculosis and must begin rifampin-based therapy. Which of the following best describes the appropriate adjustment to his dolutegravir regimen and the mechanism that requires it?
Correct Answer
A — Increase dolutegravir to 50 mg twice daily, because rifampin induces UGT1A1 and CYP3A4 and reduces dolutegravir exposure by approximately 54 percent
Rationale
Rifampin is a potent inducer of UGT1A1 and CYP3A4, both of which metabolize dolutegravir. Co-administration reduces dolutegravir plasma exposure by approximately 54 percent, risking subtherapeutic concentrations and virologic failure. The approved strategy is to double the dolutegravir dose to 50 mg twice daily, which restores adequate drug exposure. Bictegravir is not a suitable substitute because rifampin reduces bictegravir exposure by approximately 75 percent and dose adjustment within the fixed-dose tablet has not been validated, making bictegravir contraindicated with rifampin. Rifampin is an inducer, not an inhibitor, of CYP3A4.
Question 17
A 36-year-old man with HIV infection has been virologically suppressed on an atazanavir-based antiretroviral regimen for eight months. He presents to clinic reporting that his eyes have turned yellow. His total bilirubin is 3.4 mg/dL with a direct fraction of 0.3 mg/dL. Liver enzymes, hemoglobin, and reticulocyte count are within normal limits. Which of the following best explains this finding?
Correct Answer
C — Atazanavir inhibits the hepatic enzyme responsible for bilirubin conjugation, causing unconjugated bilirubin to accumulate in plasma without hepatocellular injury
Rationale
Atazanavir inhibits UGT1A1, the hepatic enzyme that conjugates unconjugated bilirubin to the water-soluble glucuronide form required for biliary excretion. When UGT1A1 is inhibited, unconjugated bilirubin accumulates in plasma, producing jaundice and scleral icterus. The fractionated bilirubin confirms the pattern: the elevated total bilirubin with a minimally elevated direct (conjugated) fraction is consistent with unconjugated hyperbilirubinemia. Normal liver enzymes and normal hemolysis markers exclude hepatocellular injury and hemolysis. This is a benign, reversible, and drug-class-specific effect — patients with underlying Gilbert syndrome, who have reduced baseline UGT1A1 activity, experience more pronounced hyperbilirubinemia with atazanavir. The finding does not indicate liver damage and does not require drug discontinuation unless the cosmetic effect is unacceptable to the patient.
Question 18
A physician is selecting an integrase strand transfer inhibitor for a treatment-naive patient newly diagnosed with HIV infection. She considers raltegravir but chooses dolutegravir instead. Which of the following best explains the pharmacological basis for preferring dolutegravir over raltegravir in a treatment-naive patient?
Correct Answer
B — Dolutegravir has a higher genetic resistance barrier than raltegravir, requires no pharmacokinetic booster, and can be dosed once daily
Rationale
Dolutegravir is classified as a second-generation integrase strand transfer inhibitor and is preferred over raltegravir in treatment-naive patients for three pharmacological reasons. First, it has a substantially higher genetic resistance barrier — virologic failure on dolutegravir rarely selects for integrase resistance mutations in treatment-naive patients, whereas resistance emerges more readily during raltegravir failure. Second, dolutegravir does not require a pharmacokinetic booster, simplifying the regimen and avoiding the drug-drug interaction burden that boosters introduce. Third, dolutegravir is dosed once daily, whereas raltegravir requires twice-daily dosing, which is a meaningful adherence advantage. Option C incorrectly attributes co-receptor tropism selectivity to integrase inhibitors — tropism is relevant only to CCR5 antagonists such as maraviroc. Option D is incorrect because both first- and second-generation integrase strand transfer inhibitors selectively inhibit the strand transfer step; neither class inhibits 3′-processing.