Chapter 36 — Antiviral Pharmacology — Module 3 — HIV Pharmacology Part 3: ARV Drug Interactions, Toxicity, and Special Populations
1. [CASE 1 — QUESTION 1]
A 35-year-old man with newly diagnosed HIV (CD4 40 cells/mm3, viral load 220,000 copies/mL) presents with cough, weight loss, and night sweats. Sputum confirms pulmonary tuberculosis, and he is started on standard four-drug therapy with isoniazid, rifampin, pyrazinamide, and ethambutol. He is antiretroviral-naive. The team initially considers a ritonavir-boosted darunavir regimen. What is the correct assessment of combining rifampin with a boosted protease inhibitor (PI)?
A) Rifampin can be combined with the boosted PI without adjustment because ritonavir overcomes the interaction
B) Rifampin raises PI concentrations, so the PI dose must be halved
C) Rifampin is contraindicated with boosted PIs because it reduces PI exposure by 75 to 90%
D) Rifampin has no effect on protease inhibitors
ANSWER: C
Rationale:
Option C is correct. Rifampin is the most potent clinically available CYP3A4 inducer and reduces protease inhibitor exposure by 75 to 90% regardless of pharmacokinetic boosting, driving concentrations to subtherapeutic levels. All boosted PI regimens are therefore contraindicated with rifampin, and an alternative antiretroviral strategy or rifabutin must be used.
Option A: Option A is incorrect. Boosting does not overcome the magnitude of rifampin induction on protease inhibitors.
Option B: Option B is incorrect. Rifampin lowers rather than raises protease inhibitor concentrations, so dose reduction is the wrong direction.
Option D: Option D is incorrect. Rifampin profoundly reduces protease inhibitor exposure and is far from inert in this setting.
2. [CASE 1 — QUESTION 2]
Continuing with the same patient. The team elects to use a dolutegravir-based regimen and rifampin cannot be replaced by rifabutin. How should the dolutegravir be dosed?
A) Dolutegravir 50 mg twice daily
B) Dolutegravir 50 mg once daily, unchanged
C) Dolutegravir 25 mg once daily
D) Dolutegravir held until rifampin is completed
ANSWER: A
Rationale:
Option A is correct. Rifampin induces UGT1A1 and CYP3A4 and reduces dolutegravir exposure by approximately 54%. Doubling the dose to dolutegravir 50 mg twice daily restores adequate trough concentrations and is the recommended strategy when rifampin must be co-administered with dolutegravir.
Option B: Option B is incorrect. Standard once-daily dosing gives inadequate dolutegravir exposure during rifampin co-administration.
Option C: Option C is incorrect. Lowering the dose would worsen the induction-driven loss of exposure.
Option D: Option D is incorrect. Both infections require concurrent treatment; dolutegravir is dose-adjusted rather than withheld.
3. [CASE 1 — QUESTION 3]
Continuing with the same patient. He is now on dose-adjusted dolutegravir plus a tenofovir-based backbone together with his four-drug tuberculosis regimen. Which monitoring is most important during the intensive phase of co-treatment?
A) Weekly electrocardiograms for QT prolongation
B) No additional laboratory monitoring beyond routine viral load
C) Monthly bone densitometry
D) Hepatic transaminase monitoring every 2 to 4 weeks given overlapping hepatotoxic potential
ANSWER: D
Rationale:
Option D is correct. Isoniazid, rifampin, and pyrazinamide each carry hepatotoxic potential, and several antiretrovirals add to that risk, creating a high-risk hepatotoxicity window during the intensive phase. Hepatic transaminase monitoring every 2 to 4 weeks during this period is essential to detect drug-induced liver injury early.
Option A: Option A is incorrect. Weekly electrocardiograms are not the priority; this regimen's dominant overlapping risk is hepatotoxicity, not QT prolongation.
Option B: Option B is incorrect. Overlapping hepatotoxicity makes additional liver monitoring necessary rather than optional.
Option C: Option C is incorrect. Monthly bone densitometry is not indicated during the intensive phase and does not address the principal co-treatment risk.
4. [CASE 1 — QUESTION 4]
Continuing with the same patient. Given his CD4 count of 40 cells/mm3, what is the recommended timing of antiretroviral therapy relative to tuberculosis treatment?
A) Defer antiretroviral therapy until tuberculosis treatment is complete
B) Initiate antiretroviral therapy within about 2 weeks of starting tuberculosis treatment
C) Start both on the same day before any tuberculosis control is established
D) Wait at least 6 months before starting antiretroviral therapy
ANSWER: B
Rationale:
Option B is correct. With a CD4 count below 50 cells/mm3, antiretroviral therapy is initiated within about 2 weeks of starting tuberculosis treatment. Although early initiation carries some immune reconstitution inflammatory syndrome risk, the mortality benefit of prompt therapy at this very low CD4 count outweighs that risk.
Option A: Option A is incorrect. Deferring antiretrovirals until tuberculosis treatment is complete would dangerously prolong profound immunodeficiency.
Option C: Option C is incorrect. Tuberculosis treatment is established first; same-day initiation is not the recommended approach.
Option D: Option D is incorrect. A 6-month delay is not recommended and would be especially harmful at a CD4 of 40.
5. [CASE 2 — QUESTION 1]
A 28-year-old woman who is 10 weeks pregnant is newly diagnosed with HIV. She is also chronically infected with hepatitis B virus (HBV) and is antiretroviral-naive. The team is selecting a nucleoside backbone. Which backbone is preferred for her, and why?
A) Abacavir/lamivudine, because it avoids renal effects
B) Tenofovir disoproxil fumarate/emtricitabine, because it is the preferred pregnancy backbone and provides dual anti-HBV activity
C) Zidovudine/lamivudine, because it is the only backbone safe in pregnancy
D) Lamivudine monotherapy until after delivery
ANSWER: B
Rationale:
Option B is correct. Tenofovir disoproxil fumarate/emtricitabine is the preferred backbone in pregnancy, supported by the largest body of safety and efficacy data, and it provides dual activity against HBV, which is essential in a co-infected patient.
Option A: Option A is incorrect. Abacavir/lamivudine lacks the robust HBV coverage that tenofovir provides.
Option C: Option C is incorrect. Zidovudine/lamivudine is not the only safe backbone and is not the preferred choice here.
Option D: Option D is incorrect. Lamivudine monotherapy is never appropriate for HIV and risks resistance and inadequate HBV treatment.
6. [CASE 2 — QUESTION 2]
Continuing with the same patient. The team must choose an integrase strand transfer inhibitor (INSTI). Which agent is recommended throughout pregnancy, including at the time of conception, under current guidelines?
A) Elvitegravir boosted with cobicistat
B) Cabotegravir long-acting injectable
C) Bictegravir
D) Dolutegravir
ANSWER: D
Rationale:
Option D is correct. Current Department of Health and Human Services and World Health Organization guidelines recommend dolutegravir throughout pregnancy, including at conception, after the Tsepamo data showed periconceptional neural tube defect rates of approximately 0.19%, not significantly different from background in most analyses.
Option A: Option A is incorrect. Cobicistat-boosted regimens have reduced and variable exposures in pregnancy and are not preferred.
Option B: Option B is incorrect. Cabotegravir long-acting injectable is not recommended in pregnancy because of absent safety data and an unmanageable pharmacokinetic tail.
Option C: Option C is incorrect. Bictegravir has less pregnancy data and is not the guideline-recommended INSTI at conception.
7. [CASE 2 — QUESTION 3]
Continuing with the same patient. She adheres well and her HIV viral load is below 50 copies/mL at 36 weeks' gestation. What is the appropriate delivery plan with respect to HIV transmission risk?
A) Vaginal delivery is appropriate; intrapartum intravenous zidovudine and cesarean section are not required on HIV grounds
B) Elective cesarean section at 38 weeks with intrapartum intravenous zidovudine is mandatory
C) Intrapartum intravenous zidovudine is required even though cesarean is not
D) Antiretrovirals should be stopped before delivery to protect the neonate
ANSWER: A
Rationale:
Option A is correct. With a maternal viral load below 50 copies/mL near term, vaginal delivery carries transmission risk equivalent to cesarean section, so intrapartum intravenous zidovudine and cesarean section are not required on HIV grounds. Durable viral suppression is the single most effective intervention against mother-to-child transmission.
Option B: Option B is incorrect. Elective cesarean with intrapartum zidovudine is reserved for viral load above 1,000 copies/mL or unknown viral load, not for an undetectable load.
Option C: Option C is incorrect. Intrapartum intravenous zidovudine is not required when the viral load is undetectable.
Option D: Option D is incorrect. Antiretrovirals are continued through delivery; stopping them would risk viral rebound and increased transmission.
8. [CASE 2 — QUESTION 4]
Continuing with the same patient. She delivers a healthy infant vaginally with an undetectable maternal viral load. What is the standard neonatal antiretroviral prophylaxis?
A) No neonatal prophylaxis is needed because the maternal viral load was undetectable
B) Triple-drug prophylaxis with zidovudine, nevirapine, and lamivudine for 12 weeks
C) Zidovudine prophylaxis for 4 to 6 weeks
D) Lifelong antiretroviral therapy started at birth
ANSWER: C
Rationale:
Option C is correct. Neonatal zidovudine prophylaxis for 4 to 6 weeks is standard for all infants born to HIV-positive mothers, including those with undetectable maternal viral loads, to further reduce transmission risk.
Option A: Option A is incorrect. Even with an undetectable maternal viral load, standard neonatal zidovudine prophylaxis is still given.
Option B: Option B is incorrect. Dual or triple prophylaxis is reserved for higher-risk infants, such as those whose mothers had a viral load above 1,000 copies/mL or received no prenatal antiretroviral therapy.
Option D: Option D is incorrect. Prophylaxis is a defined short course; lifelong therapy is started only if the infant is confirmed to be HIV-infected.
9. [CASE 3 — QUESTION 1]
A 59-year-old man with HIV has been on tenofovir disoproxil fumarate (TDF) plus a cobicistat-boosted regimen for four years. He reports fatigue and diffuse bone pain. Laboratory studies show normoglycemic glucosuria, hypophosphatemia with phosphaturia, aminoaciduria, low-molecular-weight tubular proteinuria, and a rising serum creatinine. What is the most likely diagnosis?
A) Tenofovir-associated proximal tubular injury (Fanconi syndrome)
B) Diabetic nephropathy
C) Benign cobicistat-related creatinine elevation alone
D) Acute post-streptococcal glomerulonephritis
ANSWER: A
Rationale:
Option A is correct. The combination of normoglycemic glucosuria, phosphaturia with hypophosphatemia, aminoaciduria, tubular proteinuria, and a rising creatinine is the classic picture of tenofovir disoproxil fumarate proximal tubular injury (Fanconi syndrome), and the cobicistat booster increases the risk by raising tubular tenofovir concentrations.
Option B: Option B is incorrect. Diabetic nephropathy causes glucosuria only with hyperglycemia and does not produce the full proximal tubular wasting pattern.
Option C: Option C is incorrect. The benign cobicistat creatinine artifact is an isolated creatinine rise without glucosuria, phosphaturia, or tubular proteinuria.
Option D: Option D is incorrect. Post-streptococcal glomerulonephritis presents with hematuria, red cell casts, and hypertension rather than proximal tubular solute wasting.
10. [CASE 3 — QUESTION 2]
Continuing with the same patient. What is the cellular mechanism underlying his tenofovir-associated proximal tubular injury?
A) Immune-complex deposition along the glomerular basement membrane
B) Crystal precipitation within the distal tubule lumen
C) Organic anion transporter 1 (OAT1)-mediated uptake into proximal tubular cells with inhibition of mitochondrial DNA polymerase gamma
D) Osmotic injury from contrast-induced vacuolization
ANSWER: C
Rationale:
Option C is correct. Tenofovir is concentrated in proximal tubular cells through organic anion transporter 1 (OAT1)-mediated uptake, where it inhibits mitochondrial DNA polymerase gamma, impairing mitochondrial function and producing proximal tubule injury.
Option A: Option A is incorrect. Immune-complex deposition is a glomerular mechanism, not the basis of tenofovir tubular toxicity.
Option B: Option B is incorrect. The injury is mitochondrial within proximal tubular cells, not distal luminal crystal precipitation.
Option D: Option D is incorrect. Osmotic contrast injury is unrelated to tenofovir's transporter-mediated mitochondrial mechanism.
11. [CASE 3 — QUESTION 3]
Continuing with the same patient. Why did his cobicistat-boosted regimen heighten the risk of tenofovir nephrotoxicity beyond that of tenofovir disoproxil fumarate alone?
A) Cobicistat increased renal blood flow and glomerular filtration of tenofovir
B) Cobicistat converted tenofovir disoproxil fumarate into tenofovir alafenamide
C) Cobicistat accelerated tenofovir clearance, shortening tubular exposure
Option D is correct. Boosters such as cobicistat and ritonavir inhibit the apical efflux transporter MRP2 (multidrug resistance-associated protein 2), so tenofovir accumulates to higher intracellular concentrations within proximal tubular cells, compounding mitochondrial injury beyond tenofovir disoproxil fumarate alone.
Option A: Option A is incorrect. Cobicistat does not increase glomerular filtration of tenofovir; it raises tubular drug exposure by blocking efflux.
Option B: Option B is incorrect. Cobicistat does not convert one tenofovir prodrug into another.
Option C: Option C is incorrect. Impaired efflux increases, rather than shortens, tubular tenofovir exposure.
12. [CASE 3 — QUESTION 4]
Continuing with the same patient. His tenofovir disoproxil fumarate is to be replaced. Which change best reduces ongoing proximal tubular exposure while maintaining antiviral activity?
A) Increase the tenofovir disoproxil fumarate dose to overcome reduced clearance
B) Switch to tenofovir alafenamide, which produces about 90% lower plasma tenofovir while delivering adequate active metabolite to target cells
C) Continue tenofovir disoproxil fumarate but add a second booster
D) Switch to high-dose tenofovir disoproxil fumarate given every other day
ANSWER: B
Rationale:
Option B is correct. Tenofovir alafenamide delivers the active metabolite to target cells while producing roughly 90% lower plasma tenofovir concentrations, markedly reducing proximal tubular exposure and the associated nephrotoxicity and bone loss, making it the appropriate switch.
Option A: Option A is incorrect. Increasing the tenofovir disoproxil fumarate dose would raise tubular exposure and worsen injury.
Option C: Option C is incorrect. Adding a second booster would further inhibit tubular efflux and increase tenofovir accumulation.
Option D: Option D is incorrect. Higher intermittent tenofovir disoproxil fumarate dosing does not reduce tubular exposure and is not an appropriate strategy.
13. [CASE 4 — QUESTION 1]
A 42-year-old woman with HIV is maintained on methadone for opioid use disorder and takes a daily proton pump inhibitor (PPI) for gastroesophageal reflux disease. She is started on an efavirenz-based regimen. About ten days later she develops yawning, rhinorrhea, myalgias, and craving. What is the most likely cause of these symptoms?
A) Methadone accumulation causing early toxicity
B) An allergic reaction to efavirenz
C) Opioid withdrawal from efavirenz-induced reduction in methadone concentrations
D) Proton pump inhibitor-induced malabsorption of methadone
ANSWER: C
Rationale:
Option C is correct. Efavirenz is an enzyme inducer that lowers methadone concentrations by 50 to 60%, precipitating opioid withdrawal within days to weeks of initiation. The timing and symptom pattern are characteristic of this predictable interaction.
Option A: Option A is incorrect. Efavirenz lowers methadone concentrations, so withdrawal rather than accumulation and toxicity results.
Option B: Option B is incorrect. The symptoms are classic opioid withdrawal, not an allergic reaction.
Option D: Option D is incorrect. The interaction is enzyme induction lowering methadone exposure, not proton pump inhibitor-induced malabsorption.
14. [CASE 4 — QUESTION 2]
Continuing with the same patient. What is the enzymatic mechanism by which efavirenz reduced her methadone concentrations?
A) Induction of CYP3A4 and CYP2B6, accelerating methadone metabolism
B) Inhibition of CYP3A4, slowing methadone metabolism
C) Displacement of methadone from plasma protein binding
D) Blockade of intestinal P-glycoprotein efflux of methadone
ANSWER: A
Rationale:
Option A is correct. Efavirenz induces CYP3A4 and CYP2B6, the principal enzymes that metabolize methadone, accelerating its clearance and lowering plasma concentrations by 50 to 60%, which precipitates withdrawal.
Option B: Option B is incorrect. Efavirenz induces rather than inhibits these enzymes; inhibition would raise methadone concentrations.
Option C: Option C is incorrect. Protein-binding displacement is not the mechanism of this interaction.
Option D: Option D is incorrect. The interaction is metabolic induction, not altered P-glycoprotein-mediated transport.
15. [CASE 4 — QUESTION 3]
Continuing with the same patient. The team considers switching her to a rilpivirine-based regimen, but she requires her daily proton pump inhibitor for severe reflux. Why is rilpivirine a poor choice here?
A) Rilpivirine raises methadone concentrations to toxic levels
B) Rilpivirine absorption is reduced about 76% by proton pump inhibitors because it requires gastric acidity, making the combination contraindicated
C) Rilpivirine cannot be used with any integrase inhibitor
D) Rilpivirine is contraindicated in all patients with reflux disease regardless of acid suppression
ANSWER: B
Rationale:
Option B is correct. Rilpivirine requires an acidic gastric environment for absorption, and proton pump inhibitors reduce its concentrations by roughly 76% throughout the day, making the combination contraindicated with no workaround by dose separation. Because she needs continuous proton pump inhibitor therapy, rilpivirine is inappropriate.
Option A: Option A is incorrect. The problem is impaired rilpivirine absorption, not a rise in methadone concentrations.
Option C: Option C is incorrect. Rilpivirine is not categorically incompatible with integrase inhibitors; the issue is the proton pump inhibitor interaction.
Option D: Option D is incorrect. Rilpivirine is not contraindicated in reflux per se; the specific issue is concurrent proton pump inhibitor acid suppression.
16. [CASE 4 — QUESTION 4]
Continuing with the same patient. Which regimen best resolves both her opioid-substitution interaction and her need for continuous acid suppression?
A) Nevirapine-based regimen
B) Boosted atazanavir with the proton pump inhibitor
C) Continue efavirenz and reduce the methadone dose
D) Dolutegravir-based regimen
ANSWER: D
Rationale:
Option D is correct. Dolutegravir has minimal interaction with methadone and its absorption is independent of gastric acidity, so a dolutegravir-based regimen simultaneously avoids precipitating opioid withdrawal and allows continued proton pump inhibitor use.
Option A: Option A is incorrect. Nevirapine also reduces methadone concentrations and adds hepatotoxicity risk.
Option B: Option B is incorrect. Even boosted atazanavir tolerates only low-dose, carefully timed acid suppression and is unsuitable for a patient needing daily proton pump inhibitor therapy.
Option C: Option C is incorrect. Continuing efavirenz and lowering the methadone dose would worsen withdrawal rather than resolve the interaction.
17. [CASE 5 — QUESTION 1]
A 47-year-old man with advanced AIDS (CD4 35 cells/mm3) starts antiretroviral therapy. Six weeks later, while adherent and with a falling viral load, he develops fever and worsening cervical and mediastinal lymphadenopathy; biopsy shows granulomatous inflammation with cultures growing Mycobacterium avium complex (MAC). What is the most likely explanation for this clinical worsening?
A) Antiretroviral treatment failure
B) Direct antiretroviral hepatotoxicity
C) Immune reconstitution inflammatory syndrome (IRIS) triggered by recovering immunity against MAC
D) A drug hypersensitivity reaction to the nucleoside backbone
ANSWER: C
Rationale:
Option C is correct. In a patient with advanced immunodeficiency who develops inflammatory worsening within weeks of starting antiretroviral therapy while the viral load falls, immune reconstitution inflammatory syndrome is the most likely explanation; recovering immune function mounts an exaggerated inflammatory response, here against Mycobacterium avium complex.
Option A: Option A is incorrect. A falling viral load indicates effective antiretroviral therapy, arguing against treatment failure.
Option B: Option B is incorrect. Direct hepatotoxicity would not produce inflammatory lymphadenopathy with granulomatous MAC histology.
Option D: Option D is incorrect. A nucleoside hypersensitivity reaction does not present as MAC-driven inflammatory lymphadenopathy during immune recovery.
18. [CASE 5 — QUESTION 2]
Continuing with the same patient. After recovery, his immune status improves, but he is noted to have a 10-year cardiovascular risk of 24%, normal renal function, and is HLA-B*57:01-negative. The team is choosing a nucleoside backbone. What is the most appropriate decision regarding abacavir?
A) Use abacavir preferentially because it is renally safe
B) Avoid abacavir because it is associated with increased myocardial infarction risk in high-cardiovascular-risk patients when alternatives are available
C) Use abacavir only if combined with a boosted protease inhibitor
D) Abacavir choice is irrelevant to cardiovascular risk
ANSWER: B
Rationale:
Option B is correct. Abacavir has been associated with increased myocardial infarction risk, most pronounced in patients with high baseline cardiovascular risk. With a 24% 10-year risk and available alternatives, abacavir is best avoided in favor of a tenofovir-based backbone.
Option A: Option A is incorrect. Renal safety does not override the cardiovascular concern in a high-risk patient when alternatives exist.
Option C: Option C is incorrect. Combining abacavir with a boosted protease inhibitor does not mitigate its cardiovascular signal and could worsen lipids.
Option D: Option D is incorrect. The abacavir cardiovascular association is precisely what makes the backbone choice relevant here.
19. [CASE 5 — QUESTION 3]
Continuing with the same patient. He is ultimately maintained on a ritonavir-boosted protease inhibitor regimen and needs lipid-lowering therapy. His primary physician proposes simvastatin. Why is this choice inappropriate?
A) Simvastatin is contraindicated with boosted protease inhibitors because CYP3A4 inhibition causes dangerous accumulation and rhabdomyolysis risk
B) Simvastatin has no effect on cholesterol in patients with HIV
C) Simvastatin induces protease inhibitor metabolism and causes virologic failure
D) Simvastatin requires gastric acidity that the regimen suppresses
ANSWER: A
Rationale:
Option A is correct. Simvastatin is highly dependent on CYP3A4 metabolism, so a boosted protease inhibitor raises its concentrations to dangerous levels, risking myopathy and rhabdomyolysis; it is contraindicated with boosted protease inhibitor regimens.
Option B: Option B is incorrect. Simvastatin remains pharmacologically active; the issue is dangerous accumulation, not loss of effect.
Option C: Option C is incorrect. Simvastatin does not induce protease inhibitor metabolism or cause virologic failure.
Option D: Option D is incorrect. Simvastatin absorption is not acid-dependent; the problem is CYP3A4-mediated accumulation.
20. [CASE 5 — QUESTION 4]
Continuing with the same patient. Which lipid-lowering choice is most appropriate given his boosted protease inhibitor regimen?
A) Lovastatin at standard dose
B) Simvastatin at reduced dose
C) Any statin at maximum dose, since the regimen does not affect statins
D) Rosuvastatin or pravastatin, with attention to the OATP1B1 transporter interaction that can raise rosuvastatin levels
ANSWER: D
Rationale:
Option D is correct. Rosuvastatin and pravastatin are the safest statins with boosted protease inhibitors. Rosuvastatin levels can roughly double through OATP1B1 inhibition, so dose attention is warranted, but these agents are appropriate choices, unlike the CYP3A4-dependent statins.
Option A: Option A is incorrect. Lovastatin is CYP3A4-dependent and contraindicated with boosted protease inhibitors.
Option B: Option B is incorrect. Simvastatin is contraindicated with boosted protease inhibitors even at reduced dose.
Option C: Option C is incorrect. The regimen does affect statins; maximum dosing without regard to interactions is unsafe.
21. [CASE 6 — QUESTION 1]
A 61-year-old woman with HIV and decompensated cirrhosis (Child-Pugh C) from prior hepatitis C requires a new antiretroviral regimen. The team considers a ritonavir-boosted protease inhibitor such as darunavir or lopinavir. What is the correct assessment of these agents in Child-Pugh C disease?
A) They are preferred because hepatic metabolism is reduced and exposures are lower
B) They are contraindicated in Child-Pugh C because of substantially elevated and unpredictable exposures
C) They require only routine monitoring with no dose concern
D) They are safe if the ritonavir dose is doubled
ANSWER: B
Rationale:
Option B is correct. Darunavir and lopinavir are extensively hepatically metabolized and are contraindicated in severe hepatic impairment (Child-Pugh C) because of substantially elevated and unpredictable drug exposures.
Option A: Option A is incorrect. Reduced hepatic metabolism raises exposures to dangerous levels, which is why these agents are contraindicated rather than preferred.
Option C: Option C is incorrect. The risk is significant enough to contraindicate use, not merely to require routine monitoring.
Option D: Option D is incorrect. Increasing ritonavir would further raise exposures and worsen the risk.
22. [CASE 6 — QUESTION 2]
Continuing with the same patient. Which integrase strand transfer inhibitor (INSTI) is preferred in her Child-Pugh C disease?
A) Elvitegravir boosted with cobicistat
B) Bictegravir in a fixed-dose combination
C) Dolutegravir at a doubled dose
D) Raltegravir
ANSWER: D
Rationale:
Option D is correct. Raltegravir pharmacokinetics are minimally altered by hepatic impairment, making it the preferred integrase inhibitor in Child-Pugh C disease.
Option A: Option A is incorrect. Cobicistat-boosted elvitegravir is not preferred in severe hepatic impairment due to altered metabolism of the boosted components.
Option B: Option B is incorrect. Bictegravir is delivered in fixed-dose combinations unsuited to severe hepatic impairment and lacks raltegravir's favorable hepatic profile.
Option C: Option C is incorrect. Dolutegravir is not recommended in Child-Pugh C due to insufficient data, and dose-doubling addresses enzyme induction, not hepatic impairment.
23. [CASE 6 — QUESTION 3]
Continuing with the same patient. The team considers an abacavir-containing backbone. What is the correct assessment of abacavir in her degree of hepatic impairment?
A) Abacavir is contraindicated in moderate to severe hepatic impairment because it depends on hepatic metabolism for elimination
B) Abacavir is preferred because it bypasses the liver entirely
C) Abacavir requires no consideration of hepatic function
D) Abacavir is safe in Child-Pugh C if the dose is doubled
ANSWER: A
Rationale:
Option A is correct. Abacavir is eliminated through hepatic alcohol dehydrogenase and glucuronidation and is contraindicated in moderate to severe hepatic impairment because impaired metabolism leads to unpredictable, elevated exposures.
Option B: Option B is incorrect. Abacavir depends on hepatic metabolism and does not bypass the liver.
Option C: Option C is incorrect. Hepatic function is directly relevant; significant impairment contraindicates abacavir.
Option D: Option D is incorrect. Dose-doubling does not make abacavir safe in Child-Pugh C; it remains contraindicated.
24. [CASE 6 — QUESTION 4]
Continuing with the same patient. She is stabilized on raltegravir plus a tenofovir alafenamide-based backbone and now develops focal seizures requiring an anticonvulsant. Which agent minimizes interactions with her antiretroviral regimen?
A) Carbamazepine
B) Phenytoin
C) Levetiracetam
D) Phenobarbital
ANSWER: C
Rationale:
Option C is correct. Levetiracetam has minimal cytochrome P450 interaction potential and does not meaningfully alter antiretroviral concentrations, making it a preferred anticonvulsant in patients on antiretroviral therapy.
Option A: Option A is incorrect. Carbamazepine is a potent CYP3A4 and UGT1A1 inducer that markedly reduces antiretroviral exposure.
Option B: Option B is incorrect. Phenytoin is a strong enzyme inducer that lowers antiretroviral concentrations.
Option D: Option D is incorrect. Phenobarbital is a potent inducer that reduces antiretroviral exposure.
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