How can we revise the Human Immunodeficiency Virus (HIV) treatment regimen in patients with co-existing oncologic or rheumatologic conditions?

Revising HIV Treatment in Oncologic and Rheumatologic Patients

HIV antiretroviral therapy (ART) should be continued during cancer or rheumatologic treatment, but must be modified to integrase inhibitor-based regimens without pharmacologic boosters (ritonavir or cobicistat) to minimize drug-drug interactions and overlapping toxicities, while avoiding specific agents like zidovudine, didanosine, and stavudine that compound treatment-related adverse effects. 1

Core Principle: Never Interrupt ART

ART interruptions must be avoided due to risk of immunologic compromise, opportunistic infection, and death. 1 Continuation of ART results in better tolerance of cancer treatment, higher response rates, and improved survival. 1

• Only consider holding ART when alternate regimens are absolutely unavailable and only until completion of chemotherapy. 1
• This represents a last-resort option after exhausting all modification strategies. 1

Mandatory Multidisciplinary Co-Management

All patients with HIV and cancer or rheumatologic disease require co-management by an HIV specialist, oncologist/rheumatologist, HIV pharmacist, and oncology pharmacist. 1

• Review all proposed therapies for drug-drug interactions and overlapping toxicities prior to initiation. 1
• This consultation is non-negotiable and must occur before starting treatment. 1

Preferred ART Regimen Modifications

First-Line Choice: Integrase Inhibitors Without Boosters

Switch to integrase inhibitor-based ART regimens without ritonavir or cobicistat boosters as the preferred strategy. 1, 2

• Integrase inhibitors have the lowest potential for drug-drug interactions with chemotherapy and immunosuppressive agents. 1
• Dolutegravir 50 mg once daily is an excellent option with proven efficacy in treatment-experienced patients. 3
• Small case series favor integrase inhibitor-based ART during cancer therapy. 1

Agents to Avoid

Ritonavir, cobicistat, and protease inhibitors must be avoided due to CYP3A/4 inhibition causing dangerous interactions with most chemotherapy agents. 1

• These agents increase substrate exposure of chemotherapy drugs, resulting in potentially life-threatening toxicity. 1
• Adverse reactions from drug interactions are most common with these boosted regimens. 1

Non-nucleoside reverse transcriptase inhibitors (NNRTIs) should be used with caution as they induce CYP3A/4, causing decreased efficacy of chemotherapy. 1

• NNRTIs cause the opposite interaction from inhibitors—they decrease chemotherapy exposure. 1

Zidovudine is absolutely contraindicated when myelosuppressive chemotherapy or immunosuppressive therapy is planned. 1, 4, 2

• Zidovudine causes or exacerbates myelosuppression, compounding bone marrow toxicity. 1, 4
• Vancomycin is preferred for bacterial infections when patients are on zidovudine-containing regimens to avoid additive myelosuppression. 4

Didanosine and stavudine must be avoided due to additive peripheral neuropathy with chemotherapy agents. 1, 4, 2

• Many HIV combination pills contain one or more of these problematic medications requiring regimen change. 1

Timing of ART Initiation or Modification

ART should be offered immediately if not already receiving it, but adapted according to the cancer or rheumatologic treatment plan. 1

• Consider initiating ART ≥7 days prior to cancer treatment OR after cancer therapy tolerance is established to separately assess tolerability. 1
• Exceptions requiring immediate ART start regardless of timing include progressive multifocal leukoencephalopathy (PML). 1
• Cancer or rheumatologic treatment should not be delayed for HIV workup when possible. 1

Enhanced Monitoring Requirements

More frequent HIV viral load testing (monthly for first 3 months, then every 3 months) is needed due to potential ART-chemotherapy interactions. 1

• Drug interactions may decrease ART effectiveness, requiring closer virologic monitoring. 1

CD4+ T-cell counts should be measured more frequently in patients receiving lymphopenia-inducing treatments. 1

• Decreases in CD4+ counts from cancer therapy are not reflective of HIV control (use viral load instead). 1
• However, decreased CD4+ counts still predict increased opportunistic infection risk regardless of cause. 1

Opportunistic Infection Prophylaxis

If CD4+ count <200 cells/μL, initiate prophylaxis for Pneumocystis jiroveci pneumonia (PCP) and gram-negative bacteria. 1, 2

• If CD4+ count <100 cells/μL, consider dose reduction of chemotherapy in early cycles. 1
• Follow standard opportunistic infection prophylaxis guidelines based on CD4+ count. 1

Special Considerations for Hepatitis B Co-infection

In patients co-infected with hepatitis B, select an ART regimen that treats both HIV and hepatitis B. 1

• This prevents hepatitis B flare during cancer or immunosuppressive therapy. 1

Hierarchical Approach to Drug-Drug Interactions

When potential drug-drug interactions or overlapping toxicities exist, use this order of preference: 1

1. Substitute a different antiretroviral with less interaction potential (switch to integrase inhibitor-based regimen). 1, 2
2. Adjust dosing of cancer therapy or ART based on pharmacokinetic data.
3. Consider holding ART only as absolute last resort until chemotherapy completion. 1

Common Pitfalls to Avoid

Never discontinue ART during cancer or rheumatologic therapy unless absolutely necessary. 1, 4

• Risk of immunologic compromise and opportunistic infections outweighs most drug interaction concerns. 1

Do not assume HIV patients require dose-reduced cancer therapy. 5

• PWH should receive the same standard, full-dose cancer therapy used in the general population unless specific data exist for dose adjustments. 5
• Inappropriate dose reductions contribute to worse cancer outcomes in this population. 5

Recognize that poor performance status may be from HIV, cancer, or other causes. 1

• Treatment with ART may improve poor performance status related to HIV. 1
• Determine the cause before making treatment decisions. 1

Avoid linezolid with zidovudine due to myelosuppression. 4

• Monitor platelet counts after linezolid initiation, particularly after 7.5 days of treatment. 4
• Avoid didanosine and stavudine with linezolid due to additive peripheral neuropathy. 4