What is the best next step for a patient with HIV (Human Immunodeficiency Virus) and latent tuberculosis, currently taking bictegravir (Biktarvy)/emtricitabine (Emtriva)/tenofovir alafenamide (Vemlidy) with a suppressed viral load and normal CD4 count?

Best Management for HIV Patient with Latent TB on Bictegravir/Emtricitabine/Tenofovir Alafenamide

Change ART to dolutegravir plus emtricitabine/tenofovir disoproxil fumarate and start isoniazid 900mg once weekly plus rifapentine 900mg once weekly for 12 weeks (Option C).

Rationale for ART Regimen Change

The critical issue is that bictegravir cannot be safely used with rifapentine-based latent TB treatment due to significant drug-drug interactions:

• Coadministration of bictegravir with rifampin for 28 days resulted in significantly decreased bictegravir AUC and Cmax, making this combination not recommended 1, 2
• While limited data suggest twice-daily dosing of bictegravir/TAF/FTC may maintain viral suppression with rifampin in active TB, this approach is not established for rifapentine and requires further evaluation 2
• Dolutegravir-based regimens should not be used with once-weekly rifapentine/isoniazid pending further evaluation, but this restriction applies specifically to the once-weekly dosing regimen 1

Why Dolutegravir with TDF/FTC is the Optimal Choice

Dolutegravir 50mg twice daily with TDF/FTC is the recommended regimen when rifamycin-based therapy is needed:

• For latent TB, a 1-month course of daily rifapentine plus isoniazid was equivalent to 9 months of isoniazid in persons with HIV 1
• The recommended regimens for initial ART in the setting of rifamycin-based therapy are 2 NRTIs (excluding TAF) plus dolutegravir 50mg twice daily 1
• TAF should be excluded because when administered with rifampin, plasma TAF concentrations and intracellular tenofovir diphosphate levels are decreased, though further evaluation is ongoing 1
• TDF (tenofovir disoproxil fumarate) does not require dose adjustment with rifamycins and is the preferred tenofovir formulation in this setting 1

Analysis of Each Option

Option A (Incorrect)

• Continuing bictegravir with rifapentine is contraindicated due to significantly decreased bictegravir drug levels 1, 2
• The 4-week daily rifapentine regimen is appropriate for latent TB, but cannot be used with bictegravir 1

Option B (Incorrect)

• Delaying latent TB treatment based on CD4 count is not recommended 1
• This patient has CD4 count of 321 cells/mm³, which is adequate for initiating TB treatment 1
• Latent TB treatment should be initiated promptly to prevent progression to active disease, especially in HIV-infected patients 1

Option C (Correct)

• Switching to dolutegravir plus TDF/FTC addresses the drug interaction issue 1
• The 12-week once-weekly isoniazid/rifapentine regimen (3HP) is safe and effective for latent TB in HIV patients 1
• Once-weekly rifapentine/isoniazid is safe, well-tolerated, and has an acceptable pharmacokinetic profile when used with raltegravir, and similar principles apply to dolutegravir with appropriate dosing 1

Option D (Incorrect)

• Boosted protease inhibitors should be avoided with rifampin due to significant drug interactions 1
• If a boosted PI must be used, rifabutin (150mg daily) should be substituted for rifampin, not rifapentine 1
• Darunavir/cobicistat is not the preferred option when unboosted integrase inhibitor regimens are available 1

Important Clinical Considerations

The patient's current viral suppression (<20 copies/mL) must be maintained during the switch:

• HIV viral load assessment is recommended 1 month after switching regimens 1
• This patient has no history of drug-resistant mutations, making the switch to dolutegravir straightforward 1
• The patient should continue current ART until the new regimen is available to avoid any treatment interruption 1

Timing of therapy initiation:

• TB treatment should generally be initiated first, but in latent TB (not active disease), both can be started together since the patient is already virologically suppressed 1
• The patient's CD4 count of 321 cells/mm³ indicates adequate immune function for concurrent therapy 1

Common Pitfalls to Avoid

• Do not continue bictegravir with any rifamycin-based regimen without switching ART, as this will result in subtherapeutic bictegravir levels and potential virologic failure 1, 2
• Do not use TAF-containing regimens with rifamycins; TDF is the preferred tenofovir formulation in this setting 1
• Do not delay latent TB treatment based on CD4 count thresholds, as this patient's CD4 count is adequate 1
• Ensure dolutegravir is dosed at 50mg twice daily (not once daily) when used with rifamycins 1