Can a patient who was virologically suppressed on Tenofovir (tenofovir disoproxil fumarate or tenofovir alafenamide) plus Efavirenz restart the same regimen after a one‑month interruption, assuming no drug resistance and adequate renal function?

Restarting Tenofovir and Efavirenz After One-Month Treatment Interruption

Yes, restart the same regimen immediately—a one-month interruption in a previously virologically suppressed patient does not require resistance testing or regimen change, provided renal function remains adequate. 1, 2

Immediate Restart Protocol

Restart tenofovir (TDF or TAF) plus efavirenz without delay. Treatment interruptions increase the risk of virological rebound and potential resistance development, particularly with efavirenz's low genetic barrier to resistance. 1 The one-month gap is concerning but does not automatically necessitate a regimen change if the patient was previously suppressed. 2

Pre-Restart Assessment Required

Before restarting, verify the following parameters:

• Renal function: Check serum creatinine, estimated glomerular filtration rate (eGFR), serum phosphorus, urine glucose, and urine protein. 1, 3
• Viral load: Obtain baseline HIV RNA to document any rebound during the interruption period. 1
• Hepatitis B status: If HBV coinfected, tenofovir must be continued to prevent HBV reactivation and flare. 1, 4

Renal Safety Considerations

If eGFR is ≥60 mL/min, restart the regimen without dose adjustment. 1, 5

For patients with renal impairment:

• eGFR 50-60 mL/min: Continue standard dosing but monitor more frequently (every 3 months). 1
• eGFR 30-50 mL/min: Adjust tenofovir dosing interval to every 48 hours. 5
• **eGFR <30 mL/min:** Consider switching from TDF to TAF (if eGFR >30 mL/min) or to an alternative regimen without tenofovir. 1, 3

Critical caveat: TDF should be avoided or dose-adjusted in patients with creatinine clearance below 60 mL/min, while TAF is not recommended below 30 mL/min. 1

Monitoring After Restart

Implement intensive monitoring to ensure viral resuppression:

• Week 4: Check HIV RNA to confirm viral suppression is being re-established. 1
• Months 3,6,9,12: Continue viral load monitoring every 3 months for the first year. 4
• Renal monitoring: Assess eGFR, serum phosphorus, urine glucose, and urine protein at least every 6 months, more frequently if baseline renal dysfunction exists. 1, 3

Resistance Risk Assessment

The one-month interruption poses moderate risk for efavirenz resistance development. 6 However, if the patient was virologically suppressed before the interruption and restarts promptly:

• Resistance testing is not routinely required before restart unless viral load is significantly elevated (>1000 copies/mL) or the patient had prior treatment failures. 1
• If virological failure occurs after restart (confirmed HIV RNA >200 copies/mL at 6 months), obtain resistance testing and consider switching to an integrase inhibitor-based regimen. 1

Special Considerations for HBV Coinfection

For patients with chronic hepatitis B, stopping tenofovir risks severe HBV reactivation and hepatic flare. 1

• Restart tenofovir immediately regardless of HIV viral load status. 1
• Monitor ALT and HBV DNA at restart and monthly for the first 3 months to detect any HBV flare. 1
• Never discontinue tenofovir in HBV-coinfected patients without substituting another anti-HBV agent (entecavir or TAF). 1, 3

When to Consider Regimen Change Instead

Switch to an alternative regimen rather than restarting tenofovir/efavirenz if:

• Renal dysfunction: eGFR <30 mL/min or evidence of Fanconi syndrome (glycosuria, phosphate wasting, proteinuria). 3
• Prior adherence issues: Consider switching to a more convenient regimen (e.g., bictegravir/TAF/emtricitabine single-tablet) to improve adherence. 4
• Documented resistance: If resistance testing shows NNRTI mutations (K103N, G190S), switch to an integrase inhibitor-based regimen. 6

Common Pitfalls to Avoid

• Do not delay restart while awaiting resistance testing in a previously suppressed patient—this prolongs the period of suboptimal therapy. 1
• Do not restart tenofovir without checking renal function—unrecognized renal impairment can worsen rapidly with TDF. 3, 5
• Do not assume adherence will improve without addressing the underlying cause of the one-month default—provide adherence counseling and support. 1
• Do not forget HBV screening—unrecognized HBV coinfection makes tenofovir continuation mandatory. 1