What are the guidelines for HIV management, including AIDS definition, CD4 count thresholds, and prophylaxis for opportunistic infections like Pneumocystis jirovecii and Mycobacterium avium complex?

HIV Categorization, AIDS Definition, and Opportunistic Infection Prophylaxis

HIV Categorization and AIDS Definition

AIDS is defined by a CD4 count <200 cells/µL or the presence of an AIDS-defining illness, regardless of CD4 count. 1

• HIV infection is categorized based on CD4+ T lymphocyte counts, with severe immunosuppression occurring when CD4 counts fall below 200 cells/µL 1
• The CD4 count threshold of 200 cells/µL represents the critical point where risk for severe opportunistic infections dramatically increases 2
• AIDS-defining illnesses include conditions such as Pneumocystis pneumonia, toxoplasmic encephalitis, disseminated MAC, and others that occur with advanced immunosuppression 1

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Pneumocystis jirovecii Prophylaxis

When to Start Prophylaxis

Start PCP prophylaxis when CD4 count is <200 cells/µL, or when CD4 percentage is <14%, or with a history of oropharyngeal candidiasis (thrush). 1

• Additional indications include any history of AIDS-defining illness, even if CD4 count subsequently rises 1
• For children, age-specific thresholds apply: infants <12 months need prophylaxis if CD4 <750 cells/mm³ or <15%; children 1-5 years if CD4 <500 cells/mm³ or <15%; children 6-12 years if CD4 <200 cells/mm³ or <15% 1

Prophylactic Regimen and Dosing

The preferred prophylactic regimen is trimethoprim-sulfamethoxazole (TMP-SMZ) 1 double-strength tablet (160/800 mg) daily. 1, 3

• Alternative dosing schedules for prophylaxis include TMP-SMZ 1 double-strength tablet three times weekly 1
• Alternative agents if TMP-SMZ cannot be used: dapsone 100 mg daily, or atovaquone 1,500 mg daily 1
• For dual prophylaxis against both PCP and toxoplasmosis: dapsone 50 mg daily plus pyrimethamine 50 mg weekly plus leucovorin 25 mg weekly 1

Treatment Dosing (vs. Prophylaxis)

Treatment doses for active PCP are substantially higher than prophylactic doses: TMP-SMZ 15-20 mg/kg/day (based on trimethoprim component) divided into 3-4 doses, compared to the single daily double-strength tablet used for prophylaxis. 3

• Treatment typically requires TMP-SMZ 2 double-strength tablets orally three times daily (or IV equivalent) for 21 days 3
• This represents approximately 6-fold higher daily dosing compared to prophylaxis 3

Duration of Prophylaxis

Continue prophylaxis for life unless immune reconstitution occurs with HAART, defined as CD4 count rising to >200 cells/µL for ≥3 months. 1

• Primary prophylaxis can be safely discontinued when CD4 count increases to >200 cells/µL for ≥3 months on HAART, with median CD4 count at discontinuation typically >300 cells/µL 1
• Restart prophylaxis if CD4 count decreases back to <200 cells/µL 1
• For secondary prophylaxis (after prior PCP episode), the same discontinuation criteria apply: CD4 >200 cells/µL for ≥3 months 1
• Critical caveat: If PCP occurred at a CD4 count >200 cells/µL, continue prophylaxis for life regardless of how high the CD4 count rises 1

Special Considerations for Prophylaxis

• HIV-infected infants born to HIV-positive mothers should start TMP-SMZ prophylaxis at 4-6 weeks of age 1
• AIDS patients have significantly higher rates of adverse effects with TMP-SMZ, including rash, fever, leukopenia, and elevated liver enzymes 3
• Pregnant women should receive prophylaxis as for other adults; TMP-SMZ is preferred, though some providers withhold during first trimester due to theoretical teratogenicity concerns 1
• Aerosolized pentamidine can be considered in pregnancy due to lack of systemic absorption 1

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Steroids in Pneumocystis Infection

Corticosteroids are indicated for moderate-to-severe PCP, defined as PaO2 <70 mmHg or alveolar-arterial oxygen gradient ≥35 mmHg on room air. 3

• Steroids should be started as early as possible, ideally within 72 hours of initiating PCP treatment 3
• The standard regimen is prednisone 40 mg twice daily for 5 days, then 40 mg daily for 5 days, then 20 mg daily for 11 days (total 21-day course) 3
• Steroids reduce mortality and respiratory failure in moderate-to-severe PCP by dampening the inflammatory response that occurs with treatment 3
• Do not use steroids for mild PCP (PaO2 ≥70 mmHg), as benefit has not been demonstrated 3

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Mycobacterium avium Complex (MAC) Prophylaxis

When to Start MAC Prophylaxis

Start MAC prophylaxis when CD4 count is <50 cells/µL. 1

• This represents the critical threshold where risk of disseminated MAC disease becomes substantial 1, 2
• For children, age-specific thresholds apply: children ≥6 years need prophylaxis at CD4 <50 cells/µL; children 2-6 years at CD4 <75 cells/µL; children 1-2 years at CD4 <500 cells/µL; infants <12 months at CD4 <750 cells/µL 1

MAC Prophylaxis Regimen and Dosing

The preferred regimen is azithromycin 1,200 mg orally once weekly. 1

• Alternative regimens include clarithromycin 500 mg orally twice daily, or rifabutin 300 mg orally daily 1
• Azithromycin is preferred over clarithromycin due to once-weekly dosing, fewer drug interactions (not metabolized by CYP450 system), and better tolerability 1
• Rifabutin has significant drug interactions with protease inhibitors and NNRTIs, requiring dose adjustments, and should be avoided with certain antiretrovirals 1

Duration of MAC Prophylaxis

Continue MAC prophylaxis for life unless immune reconstitution occurs with HAART, defined as CD4 count rising to >100 cells/µL for ≥6 months. 1

• Primary prophylaxis can be discontinued when CD4 count increases to >100 cells/µL for ≥6 months on HAART 1
• Restart prophylaxis if CD4 count decreases back to <100 cells/µL 1
• For secondary prophylaxis (after prior MAC disease), discontinue after completing ≥12 months of MAC treatment, remaining asymptomatic, and achieving sustained CD4 increase to >100 cells/µL for ≥6 months 1
• Some specialists recommend obtaining blood culture for MAC before discontinuing secondary prophylaxis to confirm disease is no longer active 1

Special Considerations for MAC Prophylaxis

• Clarithromycin levels increase with protease inhibitors, but no dose adjustment is currently recommended 1
• Efavirenz reduces clarithromycin levels while increasing its active metabolite; this may reduce MAC prophylaxis efficacy, making azithromycin preferable 1
• For pregnant women, azithromycin is the drug of choice based on animal studies and anecdotal human safety data 1
• Clarithromycin should be used with caution in pregnancy due to demonstrated teratogenicity in animals 1
• Children with history of disseminated MAC should receive lifelong prophylaxis; safety of discontinuation in children on HAART has not been extensively studied 1

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Key Clinical Pearls

• The CD4 count remains the best surrogate marker of immune function in HIV patients 2
• Tuberculosis can occur at any CD4 level, though risk increases significantly with CD4 <300 cells/µL 2
• Herpes zoster and pneumococcal infections can occur even with CD4 >200 cells/µL 2
• When discontinuing prophylaxis based on immune reconstitution, most patients in studies had sustained HIV viral suppression below detection limits and median CD4 counts >300 cells/µL 1
• Integration into healthcare with ≥4 outpatient visits per year is strongly associated with receiving appropriate OI prophylaxis 4
• Drug interactions are critical considerations, particularly with rifamycins and antiretrovirals 1