NAPLEX Question of the Week: Work of ART

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NAPLEX Question of the Week: Work of ART

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EV, a 49-year-old female, presents to the Pharmacotherapy clinic for a monthly follow-up visit. She was diagnosed last month with HIV-1 and was initiated on Dovato based on her viral load and hepatitis B status.

PMH: Hypertension, Depression

Vitals: BP 122/71 mmHg, HR 76 bpm

Initial labs when HIV diagnosis was made:

CD4+: 127 cells/mm3

HIV-1 RNA viral load 425,700 copies/mL 

Negative HLA-B*5701

Current medications:

Microzide 25 mg PO QD

Prozac 20 mg PO QD

Dovato 1 tablet PO QD

Another HIV-1 RNA viral load was obtained today, which turns out to be 212,000 copies/mL (CD4 pending). EV was adherent to her regimen but revealed that she has been experiencing some indigestion after eating, which gets better when she takes some Tums and famotidine.

Which of the following statement(s) is/are correct regarding Dovato? Select all that apply.

A. Dolutegravir is an integrase strand transfer inhibitor (INSTI) that works by preventing incorporation of viral DNA into CD4+ host cell genome

B. Lamivudine is a non-nucleoside reverse transcriptase inhibitor (NNRTI) that works by directly binding reverse transcriptase enzyme to block transcription of viral RNA

C. Dolutegravir absorption may be decreased by the Tums

D. Lamivudine absorption may be decreased due to the famotidine

E. Dovato discontinuation may exacerbate hepatitis B virus (HBV) 

Answer with Rationale

Human immunodeficiency virus (HIV or HIV-1) is a zoonotic retrovirus that causes acquired immunodeficiency syndrome (AIDS). HIV attacks CD4 cell causing cell dysfunction and depletion, which consequently results in greater susceptibility to other infections and diseases. CDC recommends that everyone between the ages of 13 and 64 get tested for HIV at least once. However, people with certain risk factors, such as men who have sex with men (MSM), multiple sex partners, etc., should get tested more frequent, ideally at least once a year. Currently, there is no treatment to eradicate HIV, but initiation of ART has shown to improve morbidity, mortality, as well as risk of transmission. While on ART, plasma HIV-1 RNA viral load is the most important indicator of initial, sustained response to therapy. The ultimate goal is to reduce viral load to < 200 copies/mL, which is when virologic suppression is achieved. However, virologic suppression in HIV does not equal cure!

Answer A is correct. Dolutegravir is an integrase strand transfer inhibitor (INSTI). It inhibits HIV integrase by binding to magnesium at the integrase active site and blocking the strand transfer step of retroviral DNA integration.

Answer B is incorrect. Lamivudine is a nucleoside reverse transcriptase inhibitor (NRTI). It inhibits HIV reverse transcription via viral DNA chain termination.

Answer C is correct. Common di- and trivalent cations, which include aluminum, calcium, magnesium, and iron-containing products, are often found in antacids (Tums, etc.), laxatives (magnesium citrate, etc.), and supplements (multivitamins, etc.). They can bind with dolutegravir and consequently decrease its serum concentration. It is recommended to take dolutegravir 2 hours before or 6 hours after administration of those agents.

Answer D is incorrect. Certain agents, such as itraconazole, ketoconazole, or atazanavir require an acidic environment for absorption. Lamivudine does not require an acidic environment and therefore would not be affected by the Tums or the famotidine. 

Answer E is correct. Severe acute exacerbations of HBV have been reported in patients who are co-infected with HIV-1 and HBV and have discontinued lamivudine. Closely monitor hepatic function in these patients and, if appropriate, initiate anti-HBV treatment.

Generic/Brand: Dolutegravir/Lamivudine (Dovato), Hydrochlorothiazide (Microzide), Fluoxetine (Prozac), Calcium carbonate (Tums), Famotidine (Pepcid)

NAPLEX Core Competencies Covered:

  • 1.1 – From instruments, screening tools, laboratory, genomic or genetic information, or diagnostic findings
  • 1.2 – From patients: treatment adherence, or medication-taking behavior; chief complaint, medication history, medical history, family history, social history, lifestyle habits, socioeconomic background
  • 2.1 – Pharmacology, mechanism of action, or therapeutic class
  • 2.2 – Commercial availability; prescription or non-prescription status; brand, generic, or biosimilar names; physical descriptions; or how supplied
  • 2.3 – Boxed warnings or REMS
  • 3.8 – Drug interactions
  • 3.10 – Drug pharmacokinetics or pharmacodynamics

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