A 48 week randomized study has shown that a once daily efavirenz-based regimen is just as effective as continued protease inhibitor treatment in people who already have undetectable viral load.
The ALIZE study (ANRS 099) was presented yesterday at the Second International AIDS Society Conference on HIV Pathogenesis and Treatment in Paris. It compared a once daily regimen of ddI, FTC (emtricitabine) and efavirenz with continued protease inhibitor treatment. It was thus a true test of a once daily regimen, since all the drugs could be taken at the same time. In this study, patients who retained the protease inhibitor-based regimen were not receiving a boosted protease inhibitor such as lopinavir/ritonavir, and were generally receiving nelfinavir or indinavir.
The study recruited 355 patients on stable protease inhibitor therapy with viral load below 400 copies/ml for the previous 6 months. 46% had received nucleoside analogues alone prior to beginning their HAART regimen. 177 were randomised to continue their PI-containing regimen and 178 were randomized to switch to ddI (400mg), FTC (200mg) and efavirenz (600mg), all taken once daily at bedtime.
After 48 weeks on the assigned regimen, individuals receiving ddI/FTC/efavirenz were significantly more likely to have viral load below 50 copies/ml (95% vs 87%) by intent to treat analysis. However, the study was powered only to demonstrate that the once-daily regimen was non-inferior to continued PI-based treatment, so it is not possible to say that once daily treatment represents a superior option.
No significant difference in grade 3-4 adverse events was seen, but when the comparison was widened to include milder grade 2 events, the efavirenz arm performed less well than the PI-containing arm, due largely to central nervous system problems experienced during the first few weeks after switching to efavirenz.
Significantly more people on efavirenz had HDL cholesterol above 1.5mmol/L after week 48 compared to the PI-treated group (45% vs 18%, compared to 23% vs 20% at baseline, p<0.0001). Despite lipid elevations after commencing HAART, many patients continue to display low HDL cholesterol levels, increasing their risk of cardiovascular disease. The mechanism by which the NNRTIs (efavirenz and nevirapine) cause an increase in HDL cholesterol is unknown, but has been described as an important advantage of the drug class by some doctors.
References
Molina JM et al. Emtricitabine, didanosine and efavirenz once daily versus continued PI based HAART in HIV-infected adults with undetectable plasma HIV-RNA: 48 week results of a prospective randomized multicenter trial (ALIZE-ANRS 099). Antiviral Therapy 8 (Suppl 1), S193 (abstract 37), 2003.