In which phase of HIV (Human Immunodeficiency Virus) infection, acute or advanced, is a patient more likely to experience persistent chickenpox (varicella)?

Persistent Chickenpox Occurs in Advanced HIV Disease

Persistent chickenpox (varicella) is a manifestation of advanced-stage HIV infection, not acute HIV. This occurs when patients have severe immunosuppression with CD4 counts typically below 200 cells/mm³, representing an AIDS-defining condition with high morbidity and mortality.

Understanding the Immunologic Context

Advanced HIV Disease Definition

• Advanced HIV disease is defined by the 1993 CDC AIDS criteria, which includes opportunistic infections and severe immunosuppression 1
• Patients with symptomatic HIV infection, including thrush or unexplained fever, are considered to have advanced disease requiring treatment 1
• The critical threshold for severe varicella complications occurs when CD4 counts fall below 200 cells/mm³, with the highest risk at CD4 <100 cells/mm³ 2

Why Advanced Disease, Not Acute HIV

During acute HIV infection, CD4 counts may be temporarily reduced but immune function remains relatively intact. In contrast, advanced HIV represents profound, sustained immunosuppression where:

• Chronic varicella develops in patients with severe immunodeficiency, manifesting as persistent, atypical lesions that fail to resolve despite standard therapy 3, 4
• Disseminated varicella with systemic complications (pneumonia, hepatitis, necrotizing skin lesions) occurs predominantly in those with CD4 <200 cells/mm³ 2, 5
• Mortality from varicella reaches 43% in hospitalized HIV/AIDS patients with advanced immunosuppression, despite antiviral therapy 5

Clinical Manifestations in Advanced HIV

Atypical Presentations

• Chronic varicella presents as persistent pinpoint-sized papular lesions that continue despite oral acyclovir 3
• Hyperkeratotic lesions develop in patients with severe immunodeficiency who received subtherapeutic acyclovir doses 4
• Necrotizing skin lesions occur in 54% of patients with CD4 <100 cells/mm³ versus only 7% in those with CD4 >300 cells/mm³ 2

Systemic Complications

• Varicella pneumonia develops in 58% of hospitalized HIV/AIDS patients with chickenpox, with diffuse reticulonodular infiltrates 5
• Lung involvement with nodules occurs in 29% of patients with CD4 <100 cells/mm³ 2
• Secondary infections and sepsis complicate 44% of cases with CD4 <100 cells/mm³ versus 9% with CD4 >300 cells/mm³ 2

Treatment Implications for Advanced Disease

Aggressive Antiviral Therapy Required

• Intravenous acyclovir is mandatory for persistent or disseminated varicella in advanced HIV, not oral therapy 3, 4
• High-dose IV acyclovir (10 mg/kg every 8 hours) remains the treatment of choice for severely compromised hosts 6
• Each withdrawal of IV treatment results in rapid relapse in chronic cases 3

Resistance and Alternative Agents

• Acyclovir resistance develops in patients with advanced HIV receiving prolonged therapy 4
• Foscarnet 40 mg/kg IV every 8 hours is required for acyclovir-resistant cases 6
• Cidofovir may be used as an alternative for resistant VZV infection 1

Immune Reconstitution Considerations

• Immune reconstitution inflammatory syndrome (IRIS) to varicella occurs in 25% of patients initiated on ART during active infection 2
• Among those developing IRIS, 57% died, highlighting the complexity of managing varicella in advanced HIV 2
• Antiretroviral therapy should not be discontinued during acute opportunistic infections unless drug toxicity or interactions necessitate it 1

Prevention in HIV-Infected Patients

Post-Exposure Prophylaxis

• VZIG should be administered within 96 hours to VZV-susceptible HIV-infected patients after exposure to chickenpox or shingles 1
• If VZIG is unavailable or >96 hours post-exposure, a 7-day course of oral acyclovir beginning 7-10 days after exposure is recommended 6

Vaccination Contraindications

• Live varicella vaccine is contraindicated in HIV-infected adults and children due to risk of disseminated viral infection 1
• Household contacts of susceptible HIV-infected persons should be vaccinated to prevent transmission 1

Critical Pitfalls to Avoid

• Do not use oral acyclovir monotherapy for persistent or disseminated varicella in advanced HIV—IV therapy is required 3, 4
• Do not assume standard 7-10 day treatment courses are adequate—chronic varicella requires prolonged IV therapy until complete resolution 3
• Do not delay ART initiation indefinitely, but recognize IRIS risk when starting therapy during active varicella 2
• Do not overlook drug interactions between protease inhibitors and other medications in patients with advanced disease requiring multiple therapies 1