Patients switching from other PIs to unboosted atazanavir maintain viral suppression

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Patients switching to unboosted atazanavir (Reyataz) from other protease inhibitors (PIs) were less likely to experience viral rebound or to have to change their regimen again than patients who stayed on their original PI, the EACS Conference in Dublin heard.

The conference heard the 48 week data from the SWAN (Switching to atazanavir non-boosted) study, a randomised but open-label study comparing atazanavir and other PIs.

Three hundred and seventy-two patients were randomised either to switch from their current PI or stay on it. Ninety per cent of those switching took unboosted atazanavir (400mg once a day). The other ten per cent took atazanavir boosted with ritonavir (Norvir)(300/100mg) because they were also taking tenofovir (Viread), a drug that reduces atazanavir levels in the blood.

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.

protease inhibitor (PI)

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

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.

equivalence trial

A clinical trial which aims to demonstrate that a new treatment is no better or worse than an existing treatment. While the two drugs may have similar results in terms of virological response, the new drug may have fewer side-effects, be cheaper or have other advantages. 

cholesterol

A waxy substance, mostly made by the body and used to produce steroid hormones. High levels can be associated with atherosclerosis. There are two main types of cholesterol: low-density lipoprotein (LDL) or ‘bad’ cholesterol (which may put people at risk for heart disease and other serious conditions), and high-density lipoprotein (HDL) or ‘good’ cholesterol (which helps get rid of LDL).

At randomisation 54% of the patients were taking boosted PIs, of which two-thirds were taking lopinavir/ritonavir (Kaletra), and 46% were taking unboosted PIs, of which 71% were taking nelfinavir (Viracept).

By the end of the study at 48 weeks, seven per cent of patients taking atazanavir had failed virologically (meaning they had a viral load over 50 copies/ml) compared with 16% taking the original PIs. This was statistically significant.

Of patients who had been taking boosted PIs, eight per cent failed on atazanavir versus eleven per cent on their original PI – essentially equivalent failure rates.

Of patients who had been taking unboosted PIs, only five per cent switching to atazanavir failed compared with 22% taking their original PI. This is not that surprising given the failure rates observed in other unboosted PIs.

In terms of a strict intent-to-treat analysis where any switch from the study protocol was regarded as failure, 21% of patients on the atazanavir arm failed compared with 34% on the comparator PIs (CPIs).

A high rate of ‘adverse events’ was recorded – 72% taking atazanavir versus 64% on CPIs – but these were essentially mild and did not lead to drug discontinuation in most cases. The rate of discontinuation due to adverse events was six per cent in both study arms.

Eleven per cent of those taking atazanavir experienced the jaundice which is this drug’s most characteristic side-effect but only one per cent stopped atazanavir because of it. Liver toxicity was essentially the same in both arms, with four per cent taking atazanavir versus six per cent on CPIs (14% versus 16% in patients co-infected with hepatitis C).

Blood lipids went down in patients taking atazanavir but not in those taking CPIs, though the presenters did not divide lipid results into patients taking boosted and unboosted CPIs.

At baseline 27% of the atazanavir group and 33% of the CPI group had total cholesterol above 240mg/dl (6.15 mmols/l); by the end of the study the figures were eight per cent and 29% respectively.

The results for triglycerides (TGs) were similar with 25% and 19% of patients in the atazanavir and CPI arms respectively having TGs above 250mg/dl (2.8 mmols/l) at baseline and 9% and 30% at 48 weeks.

References

Gatell G et al. Efficacy and Safety of atazanavir (ATV) based HAART in patients switched from a stable boosted/unboosted protease-inhibitor (PI) treatment. The SWAN Study. 10th European AIDS Conference, Dublin, abstract PS1/1, 2005.