Should a Patient Repeat Viral Load Before Switching to TLD?
Switch immediately to TLD without waiting for a repeat viral load—continuing a failing NNRTI-based regimen risks accumulation of additional resistance mutations, and dolutegravir's high genetic barrier to resistance makes it effective even in the presence of NRTI resistance. 1, 2
Immediate Switch is Recommended
The priority is to prevent further resistance development by promptly switching to an effective regimen. 1, 2 When virologic failure is confirmed (detectable viral load on current regimen), delaying the switch to obtain repeat testing allows ongoing viral replication and potential accumulation of resistance mutations. 2
Dolutegravir plus 2 NRTIs (with at least 1 active by genotype) is the recommended regimen after initial treatment failure with an NNRTI, which is the most common scenario when switching from regimens like ZLN (Zidovudine/Lamivudine/Nevirapine). 1, 2
The International Antiviral Society-USA Panel explicitly recommends that virologic failure should be confirmed and, if resistance is identified, a prompt switch to another active regimen is recommended to prevent accumulation of additional resistance mutations. 1
Why TLD Works Despite Detectable Viremia
Dolutegravir has a high genetic barrier to resistance that makes it effective even when NRTI resistance is present. 2, 3
In a prospective study of 60 adults switching to TLD after failing tenofovir/lamivudine/efavirenz or nevirapine, 85% achieved viral suppression at week 24 despite 89% having baseline NRTI resistance. 3
Among those with resistance to both tenofovir and lamivudine, 83% still achieved virologic suppression on TLD. 3
A larger Nigerian cohort study of 47,531 patients demonstrated that 57.8% of those with virologic failure on TLD resuppressed to undetectable levels without regimen change, highlighting the regimen's effectiveness. 4
Resistance Testing: Important But Should Not Delay Switch
While resistance testing is ideally recommended while taking the failing regimen or within 4 weeks of stopping, the absence of resistance testing should not prevent switching to TLD. 1, 2
The guidelines state that resistance testing is recommended while taking the failing ART regimen or within 4 weeks of stopping, but this is to guide optimal regimen selection, not to delay switching. 1
The high genetic barrier to resistance of dolutegravir makes it effective even when NRTI resistance is present, so waiting for resistance results is unnecessary when switching to TLD. 2
Critical Pitfall to Avoid
Never continue the failing regimen while waiting for repeat viral load or resistance testing results—this allows ongoing viral replication and resistance accumulation. 2
Never add dolutegravir alone to the failing regimen; always switch to a complete new regimen. 2
A single active agent added to a failing regimen is not recommended. 1
Post-Switch Monitoring
Check HIV viral load at 1 month after switching to TLD to confirm virologic response. 1, 2
Continue viral load monitoring every 3 months for the first year, then at least every 6 months thereafter if suppression is maintained. 2
Monitor renal function (serum creatinine and eGFR) at baseline and periodically, particularly given the switch to tenofovir. 2
Assess hepatitis B co-infection status, as the tenofovir/lamivudine combination in TLD provides dual activity against HBV. 2
Additional Benefits of Immediate Switch
TLD has superior tolerability compared to older regimens, eliminating zidovudine-related anemia and bone marrow suppression, and nevirapine-related hepatotoxicity and rash risks. 2
The single-pill regimen of TLD improves convenience and adherence. 2
Long-term follow-up data shows sustained efficacy: 75% maintained viral suppression <50 copies/mL at 72 weeks despite 89% having baseline NRTI resistance. 5
No integrase-inhibitor resistance was detected in studies despite low-level viremia in a minority of participants. 5