Switching to Tenofovir + Dolutegravir + Emtricitabine Regimen

Introduction to the Regimen

The American College of Physicians recommends switching to tenofovir/emtricitabine/dolutegravir (TDF or TAF/FTC/DTG) as a guideline-recommended initial or switch regimen with superior efficacy, tolerability, and high barrier to resistance compared to older antiretroviral regimens 1

Before any regimen change, a complete antiretroviral treatment history, including all prior regimens and duration of use, must be reviewed and confirmed, according to the Centers for Disease Control and Prevention (CDC) 2, 4
The results of all prior resistance testing (genotypic and phenotypic if available) must be reviewed to ensure no integrase strand transfer inhibitor (InSTI) or nucleoside reverse transcriptase inhibitor (NRTI) resistance, as recommended by the World Health Organization (WHO) 2, 3
Current viral suppression status must be confirmed, with HIV-1 RNA <50 copies/mL if switching from a suppressive regimen, as per the European AIDS Clinical Society (EACS) 3
Hepatitis B virus (HBV) co-infection status must be assessed, and if positive, tenofovir-containing regimens are mandatory to maintain HBV suppression, according to the American Association for the Study of Liver Diseases (AASLD) 2, 3
Renal function assessment, including estimated glomerular filtration rate (eGFR), must be performed to determine if tenofovir alafenamide (TAF) or tenofovir disoproxil fumarate (TDF) is preferred, as recommended by the National Kidney Foundation (NKF) 5

Tenofovir alafenamide (TAF) is preferred over tenofovir disoproxil fumarate (TDF) for most patients due to reduced renal and bone toxicity, according to the International AIDS Society (IAS) 1, 5
TAF/FTC/DTG should be used for patients with or at risk for kidney disease (eGFR <60 mL/min/1.73 m²) or bone disease, as recommended by the American College of Rheumatology (ACR) 4, 5

The combination of dolutegravir with tenofovir/emtricitabine demonstrates high virological efficacy, with 89-93% achieving HIV-1 RNA <50 copies/mL at 48 weeks in treatment-naive patients, according to the National Institutes of Health (NIH) 1
The regimen has a high genetic barrier to resistance, with no treatment-emergent resistance observed in clinical trials, as reported by the FDA 1
Once-daily dosing improves adherence and convenience, according to the CDC 1
Minimal drug-drug interactions are observed compared to boosted protease inhibitor regimens, as reported by the WHO 1

If a patient has viral suppression on their current regimen, switching is appropriate to manage toxicity, improve tolerability, simplify dosing, or address patient preference, provided no documented NRTI or InSTI resistance mutations are present, according to the EACS 2, 3
If a patient has virological failure, dolutegravir plus tenofovir/emtricitabine is specifically recommended for failure of NNRTI-based first-line regimens, as per the WHO 6
If a patient is pregnant or planning pregnancy, dolutegravir with TAF/FTC is the recommended regimen, with high antiviral efficacy and low rates of adverse birth outcomes, according to the ACOG 1
If a patient has tuberculosis co-infection, dolutegravir dosing must be adjusted with rifamycin-containing tuberculosis regimens, with increased dolutegravir to 50 mg twice daily during active tuberculosis treatment with rifampin, as recommended by the CDC 1

After switching to tenofovir/emtricitabine/dolutegravir, HIV-1 RNA should be monitored at 1 month to confirm maintained or achieved viral suppression, and every 3 months for the first year, then at least every 6 months if stable, according to the IAS 2, 3
Renal function monitoring, including serum creatinine and eGFR, should be performed, particularly if using TDF, as recommended by the NKF 5
Bone density assessment should be performed if risk factors are present and TDF is used, according to the ACR 4
Adherence support should be provided, as transition from other regimens may require counseling, as per the CDC 7

Switching without reviewing complete resistance testing history may compromise efficacy, according to the WHO 2, 3
Discontinuing tenofovir in HBV co-infected patients without alternative HBV suppressive therapy may risk hepatitis flare, as reported by the AASLD 2, 3
Using standard dolutegravir dosing with rifampin may require twice-daily dosing to overcome drug interaction, according to the FDA 1
Switching if eGFR <30 mL/min/1.73 m² without dose adjustment of individual components may be harmful, as recommended by the NKF 5