Dolutegravir Plus Tenofovir as Initial HIV Treatment
Yes, dolutegravir combined with tenofovir (either tenofovir alafenamide or tenofovir disoproxil fumarate) plus emtricitabine or lamivudine is a recommended initial treatment regimen for HIV infection, with an evidence rating of AIa. 1
Recommended Regimen Formulations
The specific recommended combinations are:
- Dolutegravir plus tenofovir alafenamide/emtricitabine (evidence rating: AIa) 1
- Dolutegravir plus tenofovir disoproxil fumarate/emtricitabine (alternative if tenofovir alafenamide is unavailable) 1
Both formulations achieve high rates of viral suppression with minimal toxicity, low risk of drug interactions, and a high barrier to resistance. 1
Choosing Between Tenofovir Formulations
Tenofovir alafenamide is generally preferred over tenofovir disoproxil fumarate due to:
- Fewer tenofovir-associated adverse effects, particularly proximal renal tubular toxicity 1
- Reduced impact on bone mineral density 1
- These differences are most pronounced when tenofovir is used with pharmacological boosters (not applicable with dolutegravir) 1
However, tenofovir disoproxil fumarate remains an effective option with similar virological efficacy, and may be preferred when cost is a consideration as generic formulations become more available. 1
Important Clinical Caveats
When NOT to Use This Regimen
Do not initiate dolutegravir plus tenofovir/emtricitabine if:
- Hepatitis B co-infection is present without appropriate HBV-active therapy (tenofovir plus lamivudine or emtricitabine provides HBV coverage, so this regimen is actually appropriate for HBV co-infection) 1, 2
- Resistance testing shows mutations to any component (wait for resistance results before starting) 1
Special Populations
Pregnancy: Dolutegravir with tenofovir alafenamide/emtricitabine (or tenofovir disoproxil fumarate if tenofovir alafenamide unavailable) is the recommended regimen in pregnancy and for persons planning to become pregnant (evidence rating: AIa). 1
High viral load or low CD4 count: This regimen maintains excellent efficacy even in patients with HIV RNA >100,000 copies/mL or CD4 <200 cells/μL, unlike some other regimens. 1
Tuberculosis co-infection: If receiving rifampin-based TB treatment, dolutegravir should be dosed at 50 mg twice daily (rather than once daily) when combined with tenofovir-based NRTIs. 2
Evidence Supporting This Recommendation
The superiority of dolutegravir-based regimens over older standards has been demonstrated in multiple high-quality trials:
- The SINGLE study showed dolutegravir plus nucleoside reverse transcriptase inhibitors was superior to efavirenz-based therapy 1, 3
- The SPRING-2 study demonstrated non-inferior efficacy compared to raltegravir with similar safety 4
- Dolutegravir consistently achieves viral suppression rates of 88-93% at 48 weeks 5, 4
Advantages of This Regimen
- High barrier to resistance: No treatment-emergent integrase resistance observed in multiple trials 1, 4
- Once-daily dosing: Improves adherence 4
- Minimal drug interactions: Unlike cobicistat-boosted regimens 1
- Excellent tolerability: Low discontinuation rates due to adverse events 5, 4
- Effective across viral load ranges: Maintains efficacy even with baseline HIV RNA >100,000 copies/mL 1
Common Pitfalls to Avoid
Do not use dolutegravir monotherapy or two-drug dolutegravir/lamivudine regimens as initial therapy in the following situations:
- When resistance testing is unavailable 1
- HIV RNA ≥500,000 copies/mL 1
- Hepatitis B co-infection (requires tenofovir-containing regimen) 1
- During pregnancy (limited data for two-drug regimen) 1
Do not use cobicistat-boosted regimens during pregnancy due to inadequate drug levels. 1
Do not overlook renal function monitoring when using tenofovir disoproxil fumarate, particularly in patients with baseline renal impairment or risk factors. 1