Can art have drug-to-drug interactions?

Drug-Drug Interactions with Antiretroviral Therapy (ART)

Yes, antiretroviral therapy (ART) can have significant drug-drug interactions that can impact morbidity, mortality, and quality of life in patients with HIV, particularly those undergoing cancer treatment.

Mechanisms of ART Drug Interactions

ART medications can interact with other drugs through various mechanisms:

• Different ART drug classes have distinct metabolic pathways that can lead to interactions 1:

  • HIV-1 protease inhibitors affect CYP450 enzymes, ATP-binding cassette transporters, and UDP-glucuronosyltransferase 1
  • Non-nucleoside reverse-transcriptase inhibitors interact with CYP450 enzymes, UDP-glucuronosyltransferases, and ATP-binding cassette transporters 1
  • Integrase strand-transfer inhibitors interact with UDP-glucuronosyltransferases and various transporters 1

• The most concerning interactions occur with regimens containing pharmacologic boosters (ritonavir, cobicistat) and protease inhibitors, which strongly inhibit CYP3A/4 1

• Non-nucleoside reverse transcriptase inhibitors (NNRTIs) typically induce CYP3A/4, potentially reducing the efficacy of drugs metabolized through this pathway 1

Clinical Significance and Management

The clinical impact of these interactions ranges from minimal to potentially life-threatening:

• Interactions may be classified as 1:

  • Interaction unlikely: No modification needed
  • Interaction possible: Close monitoring recommended
  • Potential for significant interaction: Close monitoring essential
  • Potential critical interaction: Dose adjustments or therapy modification required
  • Major clinically significant interaction: Co-administration contraindicated

• When treating HIV patients with cancer, drug interactions can lead to severe consequences including 1:

  • Transplant rejection
  • Delayed emergence from anesthesia
  • Cardiovascular collapse
  • Renal and liver toxicity
  • Death

Management Strategies

When managing patients on ART who require additional medications:

• A multidisciplinary approach involving oncologists, HIV specialists, and both oncology and HIV pharmacists is strongly recommended 1

• If potential drug interactions exist, options include (in order of preference) 1:

  1. Substituting a different antiretroviral with less interaction potential
  2. Selecting an alternative medication with less interaction potential
  3. Temporarily discontinuing ART (only in specific circumstances and in consultation with an HIV specialist)

• Integrase inhibitor-based ART regimens without pharmacologic boosters are preferred in patients requiring cancer treatment due to lower interaction potential 1

• Certain antiretrovirals should be avoided in specific situations 1:

  • Ritonavir, cobicistat, and protease inhibitors should be avoided when possible due to high interaction potential
  • Zidovudine should be avoided with myelosuppressive therapies
  • Didanosine and stavudine may cause additive peripheral neuropathy

Monitoring Recommendations

Patients on ART requiring additional medications should have:

• More frequent HIV viral load testing (e.g., monthly for the first 3 months, then every 3 months) 1

• More frequent CD4+ T-cell count monitoring, especially when receiving treatments that may cause lymphopenia 1

• Regular review of all medications by specialists in both HIV care and the relevant medical specialty 1

• Careful clinical, physiological, and biochemical monitoring 2

Special Considerations

• Patients with HIV and cancer represent a particularly challenging population due to the complexity of both conditions and their treatments 1

• Hepatitis co-infection adds additional complexity, as some antiretrovirals also treat hepatitis B, and hepatitis C treatment requires careful consideration of drug interactions 1

• Warfarin and statins are examples of medications with significant potential for interactions with ART due to their metabolism through CYP450 pathways 3, 4

Remember that while computerized systems can help identify potential drug interactions, clinical judgment and careful monitoring remain essential for managing patients on ART who require additional medications 2.