II. Class

  1. Anti-retroviral agent
  2. Integrase Strand Transfer Inhibitor

III. Mechanism

  1. Integrase Strand Transfer Inhibitor prevents viral DNA from integrating into host DNA
    1. Blocks the integrase enzyme

IV. Indications

  1. Anti-retroviral naive patients
  2. Anti-retroviral experienced patients

V. Preparations: Single Agents

  1. Bictegravir (Biktarvy)
  2. Dolutegravir (Tivacay)
  3. Cabotegravir (Vocabria)
    1. Available as oral agent, as well as monthly IM Injection (administered as part of Cabenuva)
  4. Raltegravir (Isentress)
    1. Dose: One 400 mg tablet orally twice daily

VI. Preparations: Cabenuva (Cabotegravir and Rilpivirine)

  1. Cabenuva combines Integrase Inhibitor and Non-Nucleoside Reverse Transcriptase Inhibitor (NNRTI)
    1. Integrase Inhibitor: Cabotegravir
    2. Non-Nucleoside Reverse Transcriptase Inhibitor (NNRTI): Rilpivirine)
  2. Dosing
    1. Two Intramuscular Injections in gluteal Muscle (one for each drug) once monthly
    2. Administered in clinic, at $4000 per month
    3. Requires one month of oral "lead-in" daily therapy to evaluate tolerability before IM Injection
  3. Efficacy
    1. Appears as effective as triple therapy combinations
  4. Drug Interactions
    1. Less effective when combined with CYP 3A4 inducers (e.g. Phenytoin)
  5. References
    1. Orkin (2020) N Engl J Med 382(12):1124-35 [PubMed]
    2. Swindells (2020) N Engl J Med 382(12):1112-23 [PubMed]
    3. (2021) presc lett 28(3): 18

VII. Efficacy

  1. Drug resistance is common

VIII. Adverse Effects: Raltegravir

  1. Diarrhea
  2. Nausea
  3. Headache
  4. Serum Creatinine phosphokinase (CPK) increases
  5. Mild Serum Creatinine increase without affecting Renal Function (Dolutegravir)
  6. Myopathy
  7. Rhabdomyolysis
  8. Insomnia

IX. Drug Interactions

  1. Typically fewer Drug Interactions than other Anti-Retroviral Agents
  2. Phenytoin
  3. Rifampin
  4. St John's Wort
  5. Avoid taking at the same time as Calcium, Magnesium, aluminum and iron containing agents

Images: Related links to external sites (from Bing)

Related Studies

Cost: Medications

isentress (on 2/22/2017 at Medicaid.Gov Survey of pharmacy drug pricing)
ISENTRESS 400 MG TABLET $22.34 each
ral (on 5/17/2017 at Medicaid.Gov Survey of pharmacy drug pricing)
RALOXIFENE HCL 60 MG TABLET Generic $1.24 each

Ontology: Integrase Inhibitors (C0376601)

Definition (MSH) Compounds which inhibit or antagonize biosynthesis or actions of integrase.
Concepts Pharmacologic Substance (T121) , Biologically Active Substance (T123)
MSH D019429
SnomedCT 427965001, 428617003
English Inhibitors, Integrase, INTEGRASE INHIB, INHIB INTEGRASE, Integrase strand transfer inhibitor (substance), Integrase inhibitor, Integrase strand transfer inhibitor (product), Integrase strand transfer inhibitor, Integrase Inhibitors, integrase inhibitors, integrase inhibitor
French Inhibiteurs de l'intégrase
Swedish Integrashämmare
Czech integrasa - inhibitory
Finnish Integraasinestäjät
Spanish inhibidor de la integrasa, inhibidor de la transferencia de cadenas por la integrasa (sustancia), inhibidor de la transferencia de cadenas por la integrasa, inhibidor de la transferencia de cadenas por la integrasa (producto), Inhibidores de Integrasa
Polish Inhibitory integrazy
Japanese インテグラーゼ阻害剤, インテグラーゼインヒビター
German Integrase-Inhibitoren
Italian Inibitori dell'integrasi
Portuguese Inibidores de Integrase

Ontology: raltegravir (C1871526)

Definition (NCI) A small molecule with activity against human immunodeficiency virus (HIV). Raltegravir is an integrase inhibitor that blocks the integration of the viral genome into the host DNA, a critical step in the pathogenesis of HIV.
Concepts Pharmacologic Substance (T121) , Nucleic Acid, Nucleoside, or Nucleotide (T114)
MSH C507898
SnomedCT 429707008, 429368003
LNC LP102418-3, MTHU036457
English Raltegravir (substance), Raltegravir, Raltegravir (product), N-(2-(4-(4-Fluorobenzylcarbamoyl)-5-hydroxy-1-methyl-6-oxo-1,6-dihydropyrimidin-2-yl)propan-2-yl)-5-methyl-1,3,4-oxadiazole-2-carboxamide, raltegravir, RALTEGRAVIR
Spanish raltegravir (producto), raltegravir, raltegravir (sustancia)

Ontology: dolutegravir (C3253985)

Concepts Organic Chemical (T109) , Pharmacologic Substance (T121)
MSH C562325
LNC LP157327-0, MTHU045713
English dolutegravir, (4R,9aS)-5-hydroxy-2-methyl-6,10-dioxo-3,4,6,9,9a,10-hexahydro-2H-1-oxa-4a,8a-diaza-anthracene-7-carboxylic acid- 2,4 difluorobenzylamide, 2H-Pyrido(1',2':4,5)pyrazino(2,1-b)(1,3)oxazine-9- carboxamide, N-((2,4-difluorophenyl)methyl)-3,4,6,8,12,12a- hexahydro-7-hydroxy-4-methyl-6,8-dioxo-, (4R,12aS)-, Dolutegravir, antiretrovirals dolutegravir, dolutegravir (medication), DOLUTEGRAVIR