What is the recommended treatment regimen for a patient with HIV using Tenofovir Disoproxil Fumarate (TDF)?

Tenofovir Disoproxil Fumarate (TDF) for HIV Treatment

Recommended TDF-Based Regimens for Initial HIV Treatment

For most treatment-naïve adults with HIV, TDF should be combined with emtricitabine (or lamivudine) plus an integrase strand transfer inhibitor (InSTI) as the preferred initial regimen. 1

First-Line Regimen Options (in order of preference):

• Dolutegravir plus TDF/emtricitabine - Highest level evidence for efficacy and tolerability 1
• Bictegravir/TAF/emtricitabine - Note: Uses TAF formulation rather than TDF 1
• Raltegravir plus TDF/emtricitabine - Alternative InSTI-based option 1

Alternative Regimens When InSTIs Are Not an Option:

• Darunavir (boosted with ritonavir) plus TDF/emtricitabine - Recommended when InSTI resistance is suspected, particularly after exposure to long-acting cabotegravir for PrEP 1
• Efavirenz/TDF/emtricitabine - Extensively studied with high efficacy, especially in patients with baseline HIV RNA >100,000 copies/mL 1
• Rilpivirine/TDF/emtricitabine - Only if HIV RNA <100,000 copies/mL and CD4 count >200/μL; must be taken with at least 390 calories 1

Critical Contraindications and Precautions

TDF is absolutely contraindicated in patients with creatinine clearance <60 mL/min, pre-existing kidney disease, osteopenia, or osteoporosis. 1, 2

Renal Monitoring Requirements:

• Baseline: Serum creatinine, estimated creatinine clearance, urinalysis with glycosuria and proteinuria testing 1
• Ongoing: Every 6 months once HIV RNA is stable 1
• Discontinue TDF immediately if renal function worsens or proximal tubular dysfunction develops 1, 2

Bone Health Considerations:

• Assess bone mineral density in patients with history of pathologic fracture or risk factors for osteoporosis 2
• Switch from TDF to TAF proactively in patients at high risk for renal or bone toxicity 1

Special Populations

Pregnancy:

Dolutegravir plus TAF/emtricitabine (or TDF/emtricitabine if TAF unavailable) is the recommended regimen during pregnancy. 1

• TDF-based regimens are acceptable alternatives when TAF is not available 1
• Cobicistat-boosted regimens should not be used during pregnancy due to inadequate drug levels 1

Tuberculosis Co-infection:

Dolutegravir (50 mg twice daily) plus TDF/emtricitabine is recommended during active tuberculosis treatment with rifamycin-containing regimens. 1

• Efavirenz (600 mg) plus TDF/emtricitabine is an alternative 1
• Avoid rilpivirine, doravirine, and cobicistat-containing regimens with rifampin 1

Hepatitis B Co-infection:

All HIV/HBV co-infected patients must receive a regimen containing TDF (or TAF) plus emtricitabine or lamivudine. 1

• Critical warning: Discontinuing TDF in patients with chronic hepatitis B risks acute hepatic flares or decompensation, particularly with cirrhosis 3
• Monitor hepatitis B surface antigen before initiating therapy 1

Monitoring Schedule

Initial Phase (First 6 weeks):

• HIV RNA level to confirm viral suppression 1

Maintenance Phase:

• HIV RNA: Every 3 months until <50 copies/mL for 1 year, then every 6 months 1
• CD4 count: Every 6 months until >250/μL for 1 year, then can discontinue if virus suppressed 1
• Renal function: Every 6 months (creatinine, eGFR, urinalysis) 1

Common Pitfalls to Avoid

1. Do not use TDF in patients with baseline creatinine clearance <60 mL/min - dose adjustment is insufficient; switch to TAF-based regimen instead 1, 2

2. Do not use rilpivirine/TDF/emtricitabine if HIV RNA >100,000 copies/mL or CD4 <200/μL - increased risk of virologic failure 1

3. Do not combine TDF with other nephrotoxic drugs without careful monitoring - includes NSAIDs, aminoglycosides, and high-dose acyclovir 2

4. Do not use efavirenz in patients with history of depression or suicidality - increased neuropsychiatric risk 1

5. Do not discontinue TDF in HBV co-infected patients without alternative HBV-active therapy - risk of severe hepatic flares 3

Drug Interactions

• Efavirenz: High rate of neuropsychiatric adverse effects including dizziness, headache, and sleep disturbances 1, 4
• Rilpivirine: Cannot be used with proton pump inhibitors; must stagger dosing with H2 blockers 1
• Cobicistat-boosted regimens: Extensive drug interactions due to strong CYP3A inhibition 5

Efficacy Data

In treatment-naïve patients, TDF/emtricitabine/efavirenz demonstrated superior virological suppression compared to zidovudine/lamivudine/efavirenz, with 84% achieving HIV RNA <50 copies/mL at 48 weeks and greater CD4 recovery (190 vs 158 cells/mm³). 6, 4