NCCN Guidelines for Managing HIV‑Associated Malignancies

ART Management During Cancer Therapy

• All patients with HIV‑associated malignancies should maintain antiretroviral therapy (ART) throughout cancer treatment; interruptions increase the risk of immunologic compromise, opportunistic infection, and death. (NCCN) 1
• Co‑management by an HIV specialist, oncologist, HIV pharmacist, and oncology pharmacist is required to review drug‑drug interactions and overlapping toxicities before any cancer therapy is started. (NCCN) 1
• Immediate communication between the oncology team and an HIV specialist must be established; every HIV‑positive cancer patient should be linked to an HIV specialist if not already connected. (NCCN) 2
• Cancer treatment should not be delayed for HIV work‑up when feasible. (NCCN) 1
• For patients not yet on ART, initiate therapy at least 7 days before the first cancer treatment cycle or after the first cycle to allow separate assessment of tolerability. (NCCN) 1
• ART should be offered immediately to ART‑naïve patients, with the regimen adapted to the planned cancer therapy. (NCCN) 1
• Exceptions requiring immediate ART initiation regardless of cancer timing include conditions such as progressive multifocal leukoencephalopathy (PML). (NCCN) 1
• Patients already receiving ART should continue therapy but modify the regimen as needed to minimize drug‑drug interactions. (NCCN) 1

Preferred and Contraindicated ART Regimens

• Preferred regimen: switch to an integrase inhibitor‑based ART without ritonavir or cobicistat boosters during cancer treatment. (NCCN) 3
• Integrase inhibitors (e.g., dolutegravir, raltegravir, bictegravir) have the lowest potential for interactions with chemotherapy agents. (NCCN) 3
• Small case series report favorable outcomes when integrase inhibitor‑based ART is used concurrently with cancer therapy. (NCCN) 3
• Avoid ritonavir, cobicistat, and protease inhibitors because CYP3A/4 inhibition creates dangerous interactions with most chemotherapy agents. (NCCN) 1
• Use non‑nucleoside reverse transcriptase inhibitors (NNRTIs) with caution; they induce CYP3A/4 and may reduce chemotherapy efficacy. (NCCN) 4
• Zidovudine is contraindicated when myelosuppressive chemotherapy is planned due to additive myelosuppression. (NCCN) 4
• Didanosine and stavudine must be avoided because they add to peripheral neuropathy risk when combined with neurotoxic chemotherapy. (NCCN) 4
• Many fixed‑dose combination pills contain the above agents and therefore require regimen modification. (NCCN) 4

Hierarchical Approach to Drug‑Drug Interactions

Monitoring During Cancer Treatment

• HIV viral load should be measured monthly for the first three months, then every three months throughout systemic cancer therapy to detect ART‑chemotherapy interaction effects. (NCCN) 1
• CD4+ T‑cell counts should be obtained more frequently in patients receiving lymphopenic cancer regimens. (NCCN) 1
• Declines in CD4+ counts due to cancer therapy do not necessarily reflect HIV control; viral load remains the primary marker, although low CD4+ predicts higher opportunistic infection risk. (NCCN) 1

Co‑infection Considerations

• In patients co‑infected with hepatitis B, choose an ART regimen that is active against both HIV and hepatitis B (e.g., tenofovir‑based combinations). (NCCN) 1

Cancer Treatment Principles

• Continuation of ART during cancer therapy is associated with better tolerance, higher response rates, and improved survival. (NCCN) 1
• Poor performance status in HIV‑positive patients may stem from HIV, cancer, or other causes; initiating or optimizing ART can improve performance status when HIV‑related. (NCCN) 4

Opportunistic Infection Prophylaxis

• CD4+ < 200 cells/µL: start prophylaxis for Pneumocystis jirovecii pneumonia and gram‑negative bacterial infections, in addition to standard opportunistic infection prophylaxis. (NCCN) 4
• CD4+ < 100 cells/µL: consider dose reduction in the early cycles of chemotherapy. (NCCN) 4
• Cancer patients have an elevated risk of opportunistic infections due to combined immunosuppression from HIV and chemotherapy; chemotherapy‑induced neutropenia is a major contributor. (NCCN) 2
• Low CD4+ counts increase the risk of febrile neutropenia after chemotherapy. (NCCN) 2

Prevention, Screening, and Lifestyle

• Smoking cessation should be discussed with all patients. (NCCN) 1
• All patients diagnosed with cancer should be screened for HIV to identify undiagnosed infection. (NCCN) 4

Critical Pitfalls to Avoid

• Never discontinue ART during cancer therapy unless absolutely necessary after exhausting all alternative strategies. (NCCN) 1
• Do not delay cancer treatment for HIV work‑up when it can be avoided. (NCCN) 1
• Be aware that PET/CT findings in HIV‑positive patients can be confounded by opportunistic infections and immune‑deficiency‑related lymphoid hyperplasia. (NCCN) 4

Managing HIV Infection in Patients with Cancer or Rheumatologic Disease

Core Principles

• The National Comprehensive Cancer Network recommends continuing HIV antiretroviral therapy (ART) during cancer or rheumatologic treatment, but modifying the regimen to minimize drug-drug interactions and overlapping toxicities 5, 6, 7
• ART interruptions should be avoided due to the risk of immunologic compromise, opportunistic infection, and death, and instead, the regimen should be adapted to the cancer or rheumatologic treatment plan 5, 6, 7

Mandatory Multidisciplinary Co-Management

• The National Comprehensive Cancer Network recommends co-management by an HIV specialist, oncologist/rheumatologist, HIV pharmacist, and oncology pharmacist for all patients with HIV and cancer or rheumatologic disease 5, 6, 7, 8
• All proposed therapies should be reviewed for drug-drug interactions and overlapping toxicities prior to initiation 9

Preferred ART Regimen Modifications

• The National Comprehensive Cancer Network recommends switching to integrase inhibitor-based ART regimens without ritonavir or cobicistat boosters as the preferred strategy 9, 10
• Integrase inhibitors have the lowest potential for drug-drug interactions with chemotherapy and immunosuppressive agents 9

Agents to Avoid

• Ritonavir, cobicistat, and protease inhibitors should be avoided due to CYP3A/4 inhibition causing dangerous interactions with most chemotherapy agents 5, 6, 7, 11, 12, 8
• Non-nucleoside reverse transcriptase inhibitors (NNRTIs) should be used with caution as they induce CYP3A/4, causing decreased efficacy of chemotherapy 5, 6, 7, 11, 12, 8
• Zidovudine is absolutely contraindicated when myelosuppressive chemotherapy or immunosuppressive therapy is planned 5, 6, 7, 11, 12, 8, 13, 10
• Didanosine and stavudine must be avoided due to additive peripheral neuropathy with chemotherapy agents 5, 6, 7, 11, 12, 8, 13, 10

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 5, 6, 7, 11, 12, 8
• Consider initiating ART ≥7 days prior to cancer treatment OR after cancer therapy tolerance is established to separately assess tolerability 5, 6, 7, 11, 12, 8

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 5, 6, 7, 11, 9, 12, 8
• CD4+ T-cell counts should be measured more frequently in patients receiving lymphopenia-inducing treatments 5, 6, 7, 9, 12

Opportunistic Infection Prophylaxis

• If CD4+ count <200 cells/μL, initiate prophylaxis for Pneumocystis jiroveci pneumonia (PCP) and gram-negative bacteria 11, 8, 10
• Follow standard opportunistic infection prophylaxis guidelines based on CD4+ count 5, 11, 8

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 5, 6, 7, 11, 9, 12, 8

Hierarchical Approach to Drug-Drug Interactions

• When potential drug-drug interactions or overlapping toxicities exist, use this order of preference: substitute a different antiretroviral with less interaction potential, adjust dosing of cancer therapy or ART based on pharmacokinetic data, and consider holding ART only as absolute last resort until chemotherapy completion 9, 10, 6, 11, 12

Common Pitfalls to Avoid

• Never discontinue ART during cancer or rheumatologic therapy unless absolutely necessary 5, 6, 7, 11, 12, 8, 13
• Do not assume HIV patients require dose-reduced cancer therapy, as they should receive the same standard, full-dose cancer therapy used in the general population unless specific data exist for dose adjustments 5, 6, 7, 11, 12
• Recognize that poor performance status may be from HIV, cancer, or other causes, and determine the cause before making treatment decisions 5, 6, 7, 11, 12
• Avoid linezolid with zidovudine due to myelosuppression, and monitor platelet counts after linezolid initiation, particularly after 7.5 days of treatment 13