EFV400 is an alternative first-line option recommended in the current WHO ARV guidelines, and included in the WHO Essential Medicine List. Systematic reviews show that it has comparable efficacy and improved safety compared to EFV at the standard dose (EFV600). EFV400 is available as a single pill fixed-dose combination (TDF + 3TC + EFV400) at a similar price range to DTG-containing regimens. There is no direct study comparing DTG and EFV400, but a network meta-analysis concluded that both drugs are equivalent in terms of safety and efficacy when compared with EFV600 in first-line therapy. As with DTG, despite clinical and programmatic advantages when compared to EFV600, experience with EFV400 is limited, and more evidence is needed for specific populations (TB and PW).
The progressive increase in pretreatment HIVDR to EFV and nevirapine detected in many countries is important when considering the continued use of EFV as a preferred treatment. In countries with pretreatment HIVDR to NNRTIs below 10%, and no availability of low-cost generic DTG in a fixed-dose combination, transition from EFV600 to EFV400 might have some financial advantages. However, this would introduce the potential for 2 transition events (from EFV600 to EFV400, then from EFV400 to DTG-based regimens). Countries with pretreatment HIVDR to NNRTIs at or above 10% should avoid the use of EFV400-containing regimens, and move to DTG as the preferred first-line regimen. In both cases, long-term HIVDR and toxicity monitoring of new ARV drugs need to be regularly reviewed, until the evidence is sufficient to demonstrate that expanded use in public health programmes creates no excessive risks.
As for DTG regimens, recently reported data demonstrate that coformulated products with reduced-dose EFV (EFV400) attain effective drug levels when compared to standard EFV600-based regimens, and present cost savings relative to current first-line EFV600 products. However, the EFV400 regimen does not address the increasing burden of HIVDR in many countries, and its supply is currently dependent on a single manufacturer.