What is the management of AIDS-defining illnesses?

Management of AIDS-Defining Illnesses

All patients with AIDS-defining illnesses must immediately initiate antiretroviral therapy (ART) regardless of CD4 count or viral load, using a maximally suppressive regimen consisting of two NRTIs plus a potent third agent (integrase inhibitor, NNRTI, or boosted PI), while simultaneously treating the specific opportunistic infection. 1

Immediate ART Initiation

• Start ART immediately in all patients with AIDS-defining conditions, which includes any condition meeting the 1993 CDC definition of AIDS 1
• Use a preferred regimen: two NRTIs combined with dolutegravir, bictegravir, or a boosted protease inhibitor 1
• Do not delay ART while treating the opportunistic infection, except in specific circumstances detailed below 1
• All antiretroviral drugs should be started simultaneously at full dose (exceptions: ritonavir, nevirapine require dose escalation) 1

Timing Considerations Based on Specific Opportunistic Infections

Tuberculosis Co-infection

• For CD4 <50 cells/μL without CNS tuberculosis: Start ART within 2 weeks of tuberculosis treatment initiation to reduce mortality, despite increased IRIS risk 1, 2
• For CD4 ≥50 cells/μL: Initiate ART at 8-12 weeks after starting tuberculosis treatment 1, 2
• Use dolutegravir 50 mg twice daily (not once daily) when co-administered with rifampin-containing regimens 1
• Alternative: ritonavir-boosted atazanavir or lopinavir with rifabutin 150 mg daily if dolutegravir cannot be used 1

Cryptococcal Meningitis

• Manage increased intracranial pressure aggressively, as this is a common IRIS manifestation 2
• Continue both ART and antifungal therapy unless life-threatening complications develop 2

Disseminated MAC Disease

• Consider withholding ART until after the first 2 weeks of antimycobacterial therapy to reduce drug interactions, pill burden, and IRIS complications 2

Management of Immune Reconstitution Inflammatory Syndrome (IRIS)

Recognition and Risk Factors

• IRIS typically occurs within 3-6 months after ART initiation, presenting as paradoxical worsening of clinical symptoms despite appropriate antimicrobial therapy 1, 2
• Highest risk: CD4 <50 cells/μL at ART initiation, early ART start (within 2 weeks of OI treatment), disseminated disease with high pathogen burden 1, 2
• Common manifestations: tuberculosis (high fevers, worsening respiratory symptoms, enlarging lymphadenopathy), cryptococcal disease (increased intracranial pressure), MAC (fever, lymphadenitis) 1, 2

IRIS Treatment Algorithm

• For mild to moderate IRIS: Continue both ART and antimicrobial therapy 1, 2
• Initiate NSAIDs (ibuprofen) for symptomatic relief 2
• For severe IRIS: Administer prednisone 0.5-1.0 mg/kg/day (or 1.25 mg/kg/day for tuberculosis IRIS) for 2-6 weeks with gradual taper 2
• Only discontinue ART if life-threatening complications develop 1, 2

Specific Opportunistic Infection Management

Standard 6-Month Tuberculosis Regimen

• For HIV-infected patients receiving ART: Use standard 6-month daily regimen (2 months INH/RIF/PZA/EMB, then 4 months INH/RIF) 1
• For HIV-infected patients NOT receiving ART: Extend continuation phase to 7 months (total 9 months of therapy) 1

Prophylaxis Considerations

• Screen and treat opportunistic infections before initiating ART when feasible 2
• In the era of potent ART, prophylactic drug use has decreased significantly as the hazard of opportunistic infections has declined by 77-81% compared to monotherapy era 3
• Consider discontinuing prophylaxis in patients with sustained viral suppression and immune reconstitution 3

Drug Interaction Management

• Pay meticulous attention to drug interactions between protease inhibitors and other agents, as these are extensive and often require dose modification 1
• Rifampin is contraindicated or not recommended with all protease inhibitors; use rifabutin at reduced doses or dolutegravir twice daily instead 1
• Consult drug interaction databases (University of Liverpool, Toronto General Hospital resources) when managing cancer or other complex comorbidities 1

Monitoring During Treatment

• Do not discontinue ART during acute opportunistic infections or malignancies unless drug toxicity, intolerance, or severe drug interactions occur 1
• Monitor for new or worsening symptoms within the first 3-6 months after ART initiation 2
• Track CD4 count recovery and viral load suppression every 3-4 months 1
• Assess toxicity at least twice during the first month of therapy and every 3 months thereafter 1

Special Populations

Cancer Co-infection

• Immediately initiate ART in people with HIV and newly diagnosed cancer 1
• Prioritize cancer screening including cervical and anal cancer 1
• Assess need for opportunistic infection prophylaxis based on CD4 count, cancer type, and treatment regimen 1

Hepatitis B/C Co-infection

• The incidence of adverse events in co-infected patients receiving darunavir/ritonavir is comparable to non-co-infected patients, except for increased hepatic enzymes requiring monitoring 4

Common Pitfalls to Avoid

• Never use antiretroviral monotherapy except during pregnancy to reduce perinatal transmission 1
• Do not assume clinical deterioration with a new AIDS-defining diagnosis always indicates ART failure—it may reflect persistent severe immunocompromise despite adequate viral suppression 1
• Avoid delaying ART initiation due to concerns about pill burden or drug interactions—the mortality benefit outweighs these concerns 1
• Do not automatically discontinue prophylaxis without assessing sustained immune reconstitution 3