Should the patient's antiretroviral therapy (ART) regimen be changed to Tenofovir (nucleotide reverse transcriptase inhibitor) + Dolutegravir (integrase inhibitor) + Emtricitabine (nucleoside reverse transcriptase inhibitor)?

Should the Patient's Regimen Be Changed to Tenofovir + Dolutegravir + Emtricitabine?

Yes, switching to tenofovir/emtricitabine/dolutegravir (TDF or TAF/FTC/DTG) is strongly recommended as this represents a guideline-recommended initial or switch regimen with superior efficacy, tolerability, and high barrier to resistance compared to older antiretroviral regimens. 1

Prerequisites Before Making the Switch

Before any regimen change, the following must be reviewed and confirmed 1:

• Complete antiretroviral treatment history including all prior regimens and duration of use 1
• Results of all prior resistance testing (genotypic and phenotypic if available) to ensure no integrase strand transfer inhibitor (InSTI) or nucleoside reverse transcriptase inhibitor (NRTI) resistance 1
• Current viral suppression status - confirm HIV-1 RNA <50 copies/mL if switching from a suppressive regimen 1
• Hepatitis B virus (HBV) co-infection status - if positive, tenofovir-containing regimens are mandatory to maintain HBV suppression 1
• Renal function assessment - estimated glomerular filtration rate (eGFR) to determine if tenofovir alafenamide (TAF) or tenofovir disoproxil fumarate (TDF) is preferred 1
• Bone density risk factors - TAF preferred over TDF in patients with osteopenia, osteoporosis, or at high risk for bone disease 1
• Co-medications review to identify potential drug-drug interactions 1

Choosing Between TAF and TDF Formulations

Tenofovir alafenamide (TAF) is preferred over tenofovir disoproxil fumarate (TDF) for most patients due to reduced renal and bone toxicity 1:

• Use TAF/FTC/DTG for patients with or at risk for kidney disease (eGFR <60 mL/min/1.73 m²) or bone disease 1
• Use TDF/FTC/DTG only if TAF is unavailable or cost considerations are paramount, and patient has normal renal function and no bone disease risk 1
• TAF can be used when creatinine clearance is above 30 mL/min/1.73 m² 1

Evidence Supporting This Regimen

The combination of dolutegravir with tenofovir/emtricitabine demonstrates 1:

• High virological efficacy with 89-93% achieving HIV-1 RNA <50 copies/mL at 48 weeks in treatment-naive patients 2
• High genetic barrier to resistance - no treatment-emergent resistance observed in clinical trials 2
• Once-daily dosing improving adherence and convenience 1
• Minimal drug-drug interactions compared to boosted protease inhibitor regimens 1

Special Clinical Scenarios

If Patient Has Viral Suppression on Current Regimen

Switching is appropriate to manage toxicity, improve tolerability, simplify dosing, or address patient preference, provided 1:

• No documented NRTI or InSTI resistance mutations on prior testing 1
• Current HIV-1 RNA <50 copies/mL confirmed 1
• If HBV co-infected, must continue tenofovir-containing regimen 1

If Patient Has Virological Failure

Dolutegravir plus tenofovir/emtricitabine is specifically recommended for failure of NNRTI-based first-line regimens 1, 3:

• Superior to boosted protease inhibitor regimens (84% vs 75% suppression at 48 weeks) 3
• Effective even with M184V/I mutation present in 80% of patients 1, 3
• Resistance testing must be performed while on failing regimen or within 4 weeks of stopping 1

If Patient Has NRTI Resistance

Dolutegravir with tenofovir/emtricitabine can be effective despite baseline NRTI resistance 4:

• 83% virological suppression achieved in patients with resistance to both tenofovir and lamivudine/emtricitabine 4
• 85% suppression with lamivudine/emtricitabine resistance alone 4
• The high barrier to resistance of dolutegravir compensates for reduced NRTI activity 4

If Patient Is Pregnant or Planning Pregnancy

Dolutegravir with TAF/FTC is the recommended regimen in pregnancy 1:

• High antiviral efficacy and low rates of adverse birth outcomes 1
• Should be initiated immediately for maternal health and prevention of perinatal transmission 1
• TDF/FTC acceptable if TAF unavailable 1

If Patient Has Tuberculosis Co-infection

Dolutegravir dosing must be adjusted with rifamycin-containing tuberculosis regimens 1:

• Increase dolutegravir to 50 mg twice daily during active tuberculosis treatment with rifampin 1
• Standard once-daily dosing during tuberculosis preventive therapy with 1HP (daily rifapentine + isoniazid for 1 month) 1

Post-Switch Monitoring Protocol

After switching to tenofovir/emtricitabine/dolutegravir 1:

• HIV-1 RNA at 1 month to confirm maintained or achieved viral suppression 1
• HIV-1 RNA every 3 months for the first year, then at least every 6 months if stable 5
• Renal function monitoring - serum creatinine and eGFR, particularly if using TDF 1
• Bone density assessment if risk factors present and using TDF 1
• Adherence support - transition from other regimens may require counseling 5

Critical Pitfalls to Avoid

• Do not switch without reviewing complete resistance testing history - archived InSTI or NRTI resistance may compromise efficacy 1, 5
• Do not discontinue tenofovir in HBV co-infected patients without alternative HBV suppressive therapy - risk of hepatitis flare 1
• Do not use standard dolutegravir dosing with rifampin - requires twice-daily dosing to overcome drug interaction 1
• Do not switch if eGFR <30 mL/min/1.73 m² without dose adjustment of individual components 1
• Do not use if HIV-1 RNA >500,000 copies/mL without additional considerations, though dolutegravir-based regimens have been effective in this setting 1, 3