Boosted and unboosted atazanavir maintain viral suppression equally well

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Unboosted atazanavir (Reyataz) taken once-daily as part of a combination antiretroviral regimen can keep viral load undetectable in patients who discontinue ritonavir, researchers reported on Wednesday at the Fifth International AIDS Society Conference on HIV Pathogenesis, Treatment, and Prevention in Cape Town, South Africa.

In the ARIES trial, more than 500 treatment-naive HIV patients started a regimen of boosted atazanavir/ritonavir (300/100 mg) taken once daily plus the fixed-dose abacavir/3TC combination pill (Kivexa).

After 36 weeks, 419 participants were randomly assigned in equal numbers to either continue on boosted atazanavir or to stop taking the ritonavir. Everyone continued to take abacavir/3TC. All patients had an undetectable viral load below 50 copies/ml at the time of randomisation, and none had a history of virological treatment failure.

Glossary

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.

lipid

Fat or fat-like substances found in the blood and body tissues. Lipids serve as building blocks for cells and as a source of energy for the body. Cholesterol and triglycerides are types of lipids.

p-value

The result of a statistical test which tells us whether the results of a study are likely to be due to chance and would not be confirmed if the study was repeated. All p-values are between 0 and 1; the most reliable studies have p-values very close to 0. A p-value of 0.001 means that there is a 1 in 1000 probability that the results are due to chance and do not reflect a real difference. A p-value of 0.05 means there is a 1 in 20 probability that the results are due to chance. When a p-value is 0.05 or below, the result is considered to be ‘statistically significant’. Confidence intervals give similar information to p-values but are easier to interpret. 

efficacy

How well something works (in a research study). See also ‘effectiveness’.

bilirubin

A substance produced during the normal breakdown of red blood cells. Bilirubin passes through the liver and is excreted in faeces. Elevated levels of bilirubin (jaundice) may indicate liver damage or disease.

Most randomised patients (about 80%) were men, nearly two-thirds were white, about one-third were black, and the average age was about 40 years.

Most patients (90%) in both arms had a low Framingham score, a measure of cardiovascular risk. People in the unboosted atazanavir arm, however, were twice as likely to have a past AIDS diagnosis.

Results from the randomised portion of the study were presented at the conference. The primary endpoint was the proportion of patients with undetectable viral load at week 84the original 36 weeks on boosted atazanavir plus the 48 week randomised phaseusing an analysis called "TLOVR" (time to loss of virological response). The open-label study had statistical power to show whether unboosted atazanavir was non-inferior to the boosted drug.

At the end of 84 weeks, in an intent-to-treat analysis, study, 86% of patients taking unboosted atazanavir had viral load below 50 copies/ml compared with 81% of those taking ritonavir-boosted atazanavir, a difference that did not reach statistical significance (p=0.140). Looking at viral load below 400 copies/ml, the corresponding rates were 92% vs. 86%, which was a significant difference (p=0.036)

The researchers did an analysis that separated people with high and low baseline viral load (above or below 100,000 copies/ml), and again found that similar proportions of patients taking unboosted and boosted atazanavir had viral suppression below 50 copies/ml at the end of the study.

Only one person in the unboosted atazanavir arm experienced confirmed virological failure, compared with seven in the atazanavir/ritonavir arm. The single patient in the unboosted arm develop a reverse transcriptase resistance mutation, but none develop major protease inhibitor resistance mutations.

Median CD4 cell counts gains from baseline were also comparable in the unboosted and unboosted arms, 240 cells/mm3 vs. 259 cells/mm3.

Treatment was well-tolerated in both arms. Similar proportions of patients in the unboosted and boosted atazanavir arms experienced moderate-to-severe side-effects (26% in both groups after the initial 36 weeks, then 10% vs. 14% during the next 48 weeks). The frequency of hyperbilirubinaemia (a non-dangerous, but cosmetically distressing side-effect of atazanavir caused by a build up of bilirubin and involving a yellowing of the eyes and skin) was more than twice as common in the atazanavir/ritonavir arm (4% vs. 10%).

Compared to lipid values at the time of randomisation, median total cholesterol fell during the next 48 weeks in patients taking unboosted atazanavir, whilst it increased slightly in the boosted atazanavir arm. Triglycerides likewise decreased more in the unboosted atazanavir arm.

The investigators concluded that unboosted and unboosted atazanavir demonstrated similar efficacy regardless of baseline viral load, but patients who simplified therapy by stopping ritonavir had a more favourable lipid profile.

Further information

A powerpoint presentation by Kathleen Squires and a webcast of the conference session in which it was presented are available on the IAS 2009 website.