Prophylactic Antimicrobial Regimen for HIV with CD4 Count of 35 cells/µL
An HIV-positive adult with a CD4 count of 35 cells/µL requires triple prophylaxis: trimethoprim-sulfamethoxazole (TMP-SMX) one double-strength tablet daily for Pneumocystis pneumonia and toxoplasmosis, plus azithromycin 1200 mg weekly (or clarithromycin 500 mg twice daily) for Mycobacterium avium complex, along with immediate initiation of antiretroviral therapy. 1
Primary Prophylaxis Requirements
Pneumocystis Pneumonia (PCP) Prophylaxis
- TMP-SMX one double-strength tablet daily is the preferred regimen for all patients with CD4 counts below 200 cells/µL 1, 2
- This regimen simultaneously provides protection against toxoplasmic encephalitis (TE) in Toxoplasma-seropositive patients 1
- Alternative regimens if TMP-SMX cannot be tolerated include dapsone 100 mg daily, dapsone 50 mg daily plus pyrimethamine 50 mg weekly plus leucovorin 25 mg weekly, or atovaquone 1500 mg daily 1
Mycobacterium avium Complex (MAC) Prophylaxis
- Azithromycin 1200 mg once weekly is the preferred prophylactic agent for CD4 counts below 50 cells/µL 1
- Clarithromycin 500 mg twice daily is an equally effective alternative 1
- Rifabutin 300 mg daily can be used if macrolides cannot be tolerated, but requires careful attention to drug interactions with antiretroviral therapy 1
- The combination of clarithromycin plus rifabutin should not be used due to higher adverse effects without improved efficacy 1
Toxoplasmosis Prophylaxis
- For Toxoplasma-seropositive patients with CD4 counts below 100 cells/µL, the daily TMP-SMX double-strength tablet provides adequate protection 1
- If TMP-SMX cannot be tolerated, use dapsone 50 mg daily plus pyrimethamine 50 mg weekly plus leucovorin 25 mg weekly 1
- Toxoplasma-seronegative patients should be retested when CD4 drops below 100 cells/µL to determine if prophylaxis is needed 1
Antiretroviral Therapy Initiation
Timing and Regimen Selection
- ART should be initiated immediately at diagnosis, even on the same day if the patient is ready to commit to therapy 1
- Blood samples for HIV-1 RNA level, CD4 count, HIV genotype, and hepatitis testing should be drawn before starting ART, but treatment may begin before results are available 1
- Recommended first-line regimens include: bictegravir/TAF/emtricitabine, dolutegravir plus tenofovir/emtricitabine, or dolutegravir/lamivudine (only if HIV RNA <500,000 copies/mL and no HBV co-infection) 1
Critical Considerations for Low CD4 Counts
- Primary MAC prophylaxis is no longer recommended if effective ART is initiated immediately, though many clinicians still prescribe it at CD4 counts below 50 cells/µL 1
- For most opportunistic infections, ART should be started within the first 2 weeks after diagnosis 1
- NNRTIs and abacavir should not be used for rapid ART start before genotype results are available 1
Important Clinical Pitfalls
Drug Interactions
- Rifabutin has significant interactions with protease inhibitors and requires dose adjustments 1
- Clarithromycin interacts with certain antiretroviral agents, particularly protease inhibitors 1
- Azithromycin has fewer drug interactions than clarithromycin, making it preferable in many situations 1
Prophylaxis Discontinuation Criteria
- PCP prophylaxis can be discontinued when CD4 count increases to >200 cells/µL for ≥3 months on ART 1
- Toxoplasmosis prophylaxis can be discontinued when CD4 count increases to >200 cells/µL for ≥3 months 1
- MAC prophylaxis can be discontinued when CD4 count increases to >100 cells/µL for ≥3 months (though some guidelines use >50 cells/µL threshold) 1
Monitoring Requirements
- Exclude active tuberculosis before starting rifabutin, as it can lead to rifampin resistance 1
- Rule out disseminated MAC disease by clinical assessment before initiating prophylaxis 1
- Monitor for immune reconstitution inflammatory syndrome (IRIS) after ART initiation, particularly with very low CD4 counts 1