What are the recommended screening and treatment strategies for HIV‑associated malignancies, including antiretroviral therapy considerations and drug‑interaction management?

HIV-Associated Malignancies: Screening and Treatment Strategies

Antiretroviral Therapy Management During Cancer Treatment

All patients with HIV-associated malignancies must continue antiretroviral therapy (ART) throughout cancer treatment, as ART interruptions increase the risk of immunologic compromise, opportunistic infection, and death. 1

Mandatory Co-Management Structure

• Every HIV patient with cancer requires co-management by an HIV specialist, oncologist, HIV pharmacist, and oncology pharmacist to review all proposed therapies for drug-drug interactions and overlapping toxicities before initiation. 1, 2
• Communication between the oncology team and HIV specialist must be established immediately, with all HIV patients linked to an HIV specialist if not already connected. 1
• Cancer treatment should not be delayed for HIV workup when possible. 1

Preferred ART Regimen Modifications

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

• Integrase inhibitors (dolutegravir, raltegravir, bictegravir) have the lowest potential for drug-drug interactions with chemotherapy agents. 1, 2
• Small case series demonstrate favorable outcomes with integrase inhibitor-based ART during cancer therapy. 1

Antiretrovirals to Absolutely Avoid

The following antiretrovirals must be avoided or used with extreme caution during cancer treatment:

• Ritonavir, cobicistat, and protease inhibitors should be avoided due to CYP3A/4 inhibition causing dangerous interactions with most chemotherapy agents metabolized by that pathway. 1, 2
• Non-nucleoside reverse transcriptase inhibitors (NNRTIs) should be used with caution as they induce CYP3A/4, potentially decreasing chemotherapy efficacy. 1, 2
• Zidovudine is absolutely contraindicated when myelosuppressive chemotherapy is planned due to additive myelosuppression. 1, 2
• Didanosine and stavudine must be avoided due to additive peripheral neuropathy with chemotherapy agents. 1, 2
• Many HIV combination pills contain one or more of these medications and require modification. 1

Timing of ART Initiation or Modification

For patients not yet on ART, initiate therapy ≥7 days before starting cancer treatment OR after the first cycle of cancer therapy to facilitate separate assessment of tolerability. 1, 2

• ART should be offered immediately if the patient is not already receiving it, but adapted according to the cancer treatment plan. 1, 2
• Exceptions exist where ART should be started immediately regardless of cancer therapy timing, such as with progressive multifocal leukoencephalopathy (PML). 1
• For patients already on ART, continue therapy but modify the regimen as needed to minimize drug interactions. 1

Hierarchical Approach to Drug-Drug Interactions

When potential drug-drug interactions or overlapping toxicities exist, use this order of preference: 1, 2

1. First choice: Substitute a different antiretroviral with less drug-drug interaction potential (preferably integrase inhibitor-based regimen)
2. Second choice: Select an alternative cancer therapy regimen with less drug-drug interaction potential
3. Last resort only: Temporarily discontinue ART in consultation with an HIV specialist, but only if:
   • The above options are not advisable AND cure for the malignancy is the intent AND the chemotherapy course is of short duration, OR
   • The above options are not advisable AND the malignancy has a poor prognosis AND palliation is the goal 1

Enhanced Monitoring Requirements

HIV viral load testing must be performed more frequently during cancer treatment: 1, 2

• Check HIV viral load monthly for the first 3 months, then every 3 months during systemic cancer therapy due to potential ART-chemotherapy interactions affecting ART effectiveness. 1, 2
• CD4+ T-cell counts should be measured more frequently in patients receiving cancer treatments anticipated to cause lymphopenia. 1, 2
• Decreases in CD4+ counts attributable to cancer therapy are not necessarily reflective of HIV control, which is better measured by HIV viral load, but still predict increased risk for opportunistic infections. 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 simultaneously. 1, 2

Cancer Treatment Approach

General Principles

HIV-infected patients should receive the same standard, full-dose cancer therapy used in the general population unless specific data exist for dose adjustments. 2, 3

• Continuation of ART during cancer treatment may result in better tolerance of cancer treatment, higher response rates, and improved survival. 1
• Poor performance status in HIV patients may be from HIV, cancer, or other causes—determine the cause before making treatment decisions, as treatment with ART may improve poor performance status related to HIV. 1, 2

Opportunistic Infection Prophylaxis

Patients should receive prophylaxis indicated by their HIV status and cancer treatment: 1

• If CD4+ count <200 cells/μL: Initiate prophylaxis for Pneumocystis jirovecii pneumonia (PCP) and gram-negative bacteria in addition to appropriate opportunistic infection prophylaxis. 1, 2
• If CD4+ count <100 cells/μL: Consider dose reduction in early cycles of chemotherapy. 1
• The risk of opportunistic infections is elevated in cancer patients due to immunosuppression from both HIV and cancer treatment, with chemotherapy-induced neutropenia being a major risk factor. 1
• Low CD4+ T-cell counts increase the risk of febrile neutropenia after chemotherapy. 1

Screening Strategies for HIV-Associated Malignancies

AIDS-Defining Malignancies

The incidence of AIDS-defining malignancies has dropped precipitously since the introduction of highly active antiretroviral therapy (HAART): 4, 5

• Kaposi sarcoma incidence has declined dramatically with HAART. 4, 6, 5
• Primary central nervous system lymphoma (PCNSL) incidence has dropped significantly. 4, 5
• Systemic non-Hodgkin lymphoma (NHL) appears to be declining but to a lesser degree than Kaposi sarcoma and PCNSL. 4, 5
• Invasive cervical carcinoma incidence has not significantly changed in the HAART era. 4, 5

Non-AIDS-Defining Malignancies

Non-AIDS-defining malignancies now account for an increasing number of cancer cases in HIV-infected patients: 7, 5

• HIV-infected patients have a 1.7-3-fold higher risk of developing non-AIDS malignancies compared with the general population. 7
• These include Hodgkin lymphoma, lung cancer, anal cancer, head and neck cancers, hepatocellular carcinoma, and conjunctival cancers. 7, 5
• Most HIV-related malignancies manifest at an earlier age with a more aggressive course than non-HIV-related malignancies. 5

Prevention and Screening Interventions

Tailored cancer-prevention strategies are needed for the HIV-infected population: 8

• Smoking cessation should be discussed with all patients. 1
• Interventions known to be efficacious in other populations should systematically be used or adapted, including alcohol and tobacco cessation programs and viral coinfection management. 7
• All patients with a cancer diagnosis should be screened for HIV. 1

Common Pitfalls to Avoid

Critical errors that compromise outcomes: 2

• Never discontinue ART during cancer therapy unless absolutely necessary as a last resort after exhausting all other options. 1, 2
• Do not assume HIV patients require dose-reduced cancer therapy—they should receive standard full-dose therapy unless specific data support dose adjustments. 2, 3
• Do not delay cancer treatment for HIV workup when possible. 1
• Recognize that PET/CT findings can be confounded by non-malignant causes such as opportunistic infections and immune deficiency-related lymphoid hyperplasia in HIV patients. 1, 3