What is the management of AIDS-defining illnesses in patients with advanced HIV infection?

Management of AIDS-Defining Illnesses in Advanced HIV Infection

All patients with advanced HIV disease should be treated with antiretroviral therapy regardless of plasma viral levels, with specific attention to managing opportunistic infections and preventing drug interactions. 1

Initial Approach to AIDS-Defining Illnesses

Antiretroviral Therapy (ART)

• Initiate a maximally suppressive antiretroviral regimen consisting of two nucleoside reverse transcriptase inhibitors (NRTIs) and a protease inhibitor (PI) 1
• Start all drugs simultaneously at full dose except for:
  • Ritonavir (requires dose escalation)
  • Nevirapine (requires dose escalation)
  • Ritonavir plus saquinavir combinations 1

Timing of ART Initiation

• For patients presenting with an acute opportunistic infection (OI):
  • Consider clinical factors before starting ART:
    • Potential drug toxicity
    • Ability to adhere to treatment regimens
    • Drug interactions
    • Laboratory abnormalities 1
  • Do not discontinue existing ART during acute OI treatment unless there are concerns about drug toxicity, intolerance, or significant interactions 1

Management of Specific Opportunistic Infections

Common AIDS-Defining Opportunistic Infections

• Pneumocystis pneumonia (PCP)
• Mycobacterium avium complex (MAC)
• Tuberculosis
• Cytomegalovirus (CMV) retinitis
• Cryptococcal infection
• Toxoplasmosis
• Esophageal candidiasis 1, 2

Special Considerations for Drug Interactions

• Rifampin (for tuberculosis) has significant interactions with PIs:
  • Consider using reduced dose rifabutin instead 1
• Monitor for interactions between antiretrovirals and medications for OIs, particularly with PIs and NNRTIs that affect hepatic cytochrome P450 pathways 1

Immune Reconstitution Inflammatory Syndrome (IRIS)

IRIS is a significant complication that can occur after initiating ART in patients with advanced HIV infection:

Management of IRIS

• First-line treatment for moderate to severe IRIS:
  • Begin with NSAIDs 3
  • If symptoms persist or are severe, use short-term corticosteroids (prednisone 20-40 mg daily for 4-8 weeks) 3
• Continue ART in most cases unless life-threatening IRIS develops 3
• For CNS involvement, use higher doses of corticosteroids and consider neurosurgical consultation for increased intracranial pressure 3
• Avoid corticosteroids in Kaposi sarcoma-associated IRIS due to potential exacerbation 3

Common IRIS-Associated Infections

• Mycobacterium avium complex
• Tuberculosis
• Cryptococcosis
• Cytomegalovirus retinitis
• Pneumocystis pneumonia
• Kaposi sarcoma 3

Monitoring and Follow-up

Laboratory Monitoring

• Assess toxicity at least twice during the first month of therapy
• Continue monitoring every 3 months thereafter 1
• Regular assessment of CD4 counts and viral load 1

Patient Education

• Inform patients about potential immune reconstitution syndrome:
  • Signs and symptoms of inflammation from previous infections may occur after starting ART 4, 5
  • Advise patients to report any new symptoms immediately 4, 5
• Warn about potential drug interactions between ART and medications for opportunistic infections 1

Special Challenges in Advanced HIV Disease

• Wasting and anorexia may interfere with medication adherence and absorption of PIs 1
• Bone marrow suppression from zidovudine (ZDV) may compound HIV-related hematologic effects 1
• Neuropathic effects of certain NRTIs (ddC, d4T, ddI) may worsen HIV-related neuropathy 1
• Hepatotoxicity from PIs may be problematic in patients with underlying liver dysfunction 1

Long-term Considerations

• Despite effective ART, some risk of opportunistic infections remains even at CD4 counts >200 cells/μL, particularly for:
  • Tuberculosis
  • Herpes zoster
  • Pneumococcal disease
  • Kaposi sarcoma 1
• Monitor for emerging non-AIDS-defining cancers which have increased in the era of effective ART 6, 7

By implementing comprehensive management of both HIV infection and its associated opportunistic infections, clinicians can significantly improve outcomes for patients with advanced HIV disease.