When taking the fixed‑dose combination tenofovir + lamivudine + dolutegravir (TLD), how should I time dolutegravir with meals, antacids or mineral supplements, and rifampicin, and what is the correct action if I miss a dose?

Timing and Administration of TLD (Tenofovir/Lamivudine/Dolutegravir)

Dolutegravir can be taken with or without food, has relatively few drug interactions, and does not require dose adjustment with antacids or mineral supplements when taken as part of standard once-daily TLD therapy. 1

Food Requirements

• TLD can be taken with or without food for standard once-daily dosing 1, 2
• No meal size requirements or caloric restrictions apply to dolutegravir, unlike some other antiretrovirals 1
• This flexibility provides significant convenience compared to regimens requiring specific food intake 2

Antacids and Mineral Supplements

• Polyvalent cations (calcium, iron, magnesium, aluminum) can reduce dolutegravir absorption 3
• However, when taking standard once-daily TLD, no specific timing restrictions or dose adjustments are required for these supplements in routine clinical practice 1
• The clinical significance of these interactions is minimal with standard dosing 1

Rifampicin Co-administration

TLD cannot be used with rifampicin without dose modification because rifampicin significantly reduces dolutegravir levels through CYP3A induction 3, 4

Management Options:

• Switch to dolutegravir 50 mg twice daily (12 hours apart) with tenofovir disoproxil fumarate/lamivudine when rifampicin-based tuberculosis treatment is required 4, 5
• Recent high-quality evidence from the RADIANT-TB trial (2023) demonstrates that standard once-daily dolutegravir may provide acceptable virological outcomes even with rifampicin, showing 83% virological suppression at 24 weeks without supplemental dosing 5
• However, twice-daily dolutegravir (50 mg every 12 hours) remains the guideline-recommended approach when rifampicin is used 4
• Do not use bictegravir-containing regimens with any rifamycin as this will cause treatment failure 3, 4

Important Caveat:

• Tenofovir disoproxil fumarate (TDF) is preferred over tenofovir alafenamide (TAF) when rifamycins are used, as TAF-containing regimens should be avoided in this setting 4

Missed Dose Management

If a dose is missed and remembered within 12 hours of the scheduled time, take it immediately and continue the regular schedule 1

If more than 12 hours have passed since the scheduled dose, skip the missed dose and take the next dose at the regular time - do not double dose 1

Key Principles:

• Maintaining consistent daily dosing is critical for sustained virological suppression 6, 7
• Missing multiple doses increases risk of virological failure and resistance development 6
• Dolutegravir has a high genetic barrier to resistance when taken consistently as part of a three-drug regimen 2, 7

Common Pitfalls to Avoid

• Do not continue standard TLD with rifampicin-based tuberculosis treatment without switching to twice-daily dolutegravir dosing, as this causes subtherapeutic drug levels 4, 5
• Do not confuse TLD dosing requirements with other integrase inhibitor regimens that may have different food or timing requirements 3
• Do not use TAF-containing formulations when rifamycins are needed - switch to TDF-based regimens 4
• Do not double dose if a dose is missed by more than 12 hours, as this does not improve outcomes and may increase adverse effects 1