How should I restart antiretroviral therapy in a patient on tenofovir (TDF or TAF) plus efavirenz who had a one‑month interruption and was not virologically suppressed before the break?

Restarting ART After Treatment Interruption in a Patient Not Virologically Suppressed

Do not simply restart the same tenofovir plus efavirenz regimen—this patient requires resistance testing and a regimen change to a higher genetic barrier regimen, specifically dolutegravir plus NRTIs with at least one fully active agent. 1

Immediate Management Steps

Obtain Resistance Testing Before Restarting

• Perform genotype resistance testing immediately (ideally while still off therapy or within 4 weeks of the interruption) to identify NNRTI and NRTI mutations that likely developed during the period of non-suppression 1
• Review all prior resistance test results and complete treatment history to guide regimen selection 1
• The patient was not suppressed before the interruption, indicating pre-existing treatment failure with likely resistance mutations 1

Why the Original Regimen Failed and Should Not Be Restarted

• Efavirenz has a low genetic barrier to resistance—restarting the same NNRTI-based regimen after virologic failure will lead to rapid accumulation of additional resistance mutations 1
• The one-month interruption is less concerning than the fact that the patient was already failing therapy before the break 1
• Simply restarting efavirenz plus tenofovir in a patient with pre-existing virologic failure is contraindicated 1

Recommended New Regimen

First-Line Choice: Dolutegravir-Based Regimen

• Switch to dolutegravir plus 2 NRTIs (with at least 1 active by genotype) for failure of an initial NNRTI-based regimen 1
• Dolutegravir was superior to lopinavir plus NRTIs when the regimen included at least 1 active NRTI 1
• This provides a high genetic barrier to resistance with the integrase inhibitor backbone 1

Specific Regimen Options Based on Resistance Results

• If no significant NRTI resistance detected: Use dolutegravir/abacavir/lamivudine or dolutegravir with tenofovir alafenamide/emtricitabine 1
• If NRTI mutations present but ≥1 NRTI remains active: Use dolutegravir with that active NRTI plus a second NRTI 1
• If extensive resistance: Consider a boosted protease inhibitor (darunavir/ritonavir or darunavir/cobicistat) plus optimized NRTIs 1

Critical Pitfalls to Avoid

Do Not Restart the Same Failing Regimen

• Never add a single active agent to a failing regimen—this leads to rapid resistance development 1, 2
• Restarting efavirenz after NNRTI failure without resistance testing guarantees treatment failure with additional mutations 1
• The low genetic barrier of efavirenz makes it inappropriate for anyone with prior virologic failure 1

Address Adherence Issues

• Investigate reasons for non-suppression before the interruption: adherence barriers, drug-drug interactions, or malabsorption 1
• The treatment interruption itself suggests adherence challenges that must be addressed to ensure success of the new regimen 3
• Consider regimen simplification to single-tablet options to improve adherence 1

Monitoring After Restart

Early Virologic Response Assessment

• Check HIV RNA at 2-4 weeks after restarting therapy to confirm early virologic response 2
• Repeat viral load at 4-8 weeks, then monthly until viral suppression (<50 copies/mL) is achieved 1
• Goal is undetectable viral load by 12-24 weeks from restart 2

Ongoing Monitoring

• Once suppressed, monitor viral load every 3 months for the first year, then every 6 months 1
• Monitor CD4 count every 6 months until >250 cells/μL for 1 year while suppressed 1
• Assess renal and hepatic function regularly, especially with tenofovir-containing regimens 2

Special Considerations

If Resistance Testing Is Delayed or Unavailable

• Start a boosted protease inhibitor-based regimen (darunavir/ritonavir plus 2 NRTIs) as this provides the highest genetic barrier while awaiting results 1
• Consider proviral DNA genotyping if standard resistance testing fails due to low viral load, though interpretation requires caution 1

Hepatitis B Co-infection

• Ensure the new regimen includes agents active against HBV (tenofovir plus lamivudine or emtricitabine) if HBsAg positive 1, 4, 5
• Do not use dolutegravir/lamivudine dual therapy in HBV co-infection—requires tenofovir-based triple therapy 1, 4