Once daily therapy just as effective as continued PI therapy

Keith Alcorn
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This article is more than 21 years old.

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.

Glossary

protease inhibitor (PI)

Family of antiretrovirals which target the protease enzyme. Includes amprenavir, indinavir, lopinavir, ritonavir, saquinavir, nelfinavir, and atazanavir.

intent to treat analysis

All participants in a clinical trial are included in the final analysis, in the groups they were originally assigned to, whether or not they actually completed their course of treatment. This method provides a better estimate of the real-world effect of a treatment than an ‘on treatment’ analysis.

central nervous system (CNS)

The brain and spinal cord. CNS side-effects refer to mood changes, anxiety, dizzyness, sleep disturbance, impact on mental health, etc.

boosting agent

Booster drugs are used to ‘boost’ the effects of protease inhibitors and some other antiretrovirals. Adding a small dose of a booster drug to an antiretroviral makes the liver break down the primary drug more slowly, which means that it stays in the body for longer times or at higher levels. Without the boosting agent, the prescribed dose of the primary drug would be ineffective.

pathogenesis

The origin and step-by-step development of disease.

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

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.

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