Switching to once-daily etravirine a safe and effective option for individuals taking suppressive protease inhibitor therapy

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Patients taking a virologically suppressive HIV treatment combination can safely switch from a protease inhibitor to the new NNRTI etravirine, according to interim results from a small Spanish study presented to the 51st Interscience Conference on Antimicrobial Agents and Chemotherapy (ICAAC) in Chicago.

Six months after the switch, all patients still had an undetectable viral load. Encouragingly, changing to etravirine was associated with improvements in levels of total cholesterol and triglycerides.

Etravirine (Intelence) is a second-generation non-nucleoside reverse transcriptase inhibitor (NNRTI). It is highly effective against virus with resistance to older NNRTIs, and has been licensed for use by patients with previous experience of antiretroviral therapy. The drug is taken in combination with other anti-HIV drugs, and the approved dose is 200mg twice daily.

Glossary

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.

triglycerides

A blood fat (lipid). High levels are associated with atherosclerosis and are a risk factor for heart disease.

 

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).

concentration (of a drug)

The level of a drug in the blood or other body fluid or tissue.

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.

However, etravirine has also been shown to be effective in first-line HIV therapy, and in a once-daily dose. This ease of dosing, the drug’s high barrier to resistance and friendly lipid profile make it an attractive option for both treatment-naive and treatment-experienced patients.

Investigators from Barcelona wished to see if patients taking virologically suppressive HIV therapy based on a boosted protease inhibitor could safely and effectively switch to a combination that included etravirine.

They therefore designed a small, randomised study involving 46 patients. All the patients had been taking protease inhibitor-based therapy for at least twelve months with an undetectable viral load for at least six months.

Study participants were randomised to switch to once-daily etravirine or to continue taking a protease inhibitor. The study’s primary outcome was viral load 24 weeks after randomisation, and changes in CD4 cell count, cholesterol and triglycerides were also monitored. In addition, the investigators gathered data on patient satisfaction.

A total of 24 patients were randomised to receive etravirine, with the other 22 individuals continuing to take a protease inhibitor.

Six months after randomisation, all the patients still had an undetectable viral load. There was a slight increase in median CD4 cell count in both study arms (etravirine: 702 to 795 cells/mm3; protease inhibitor: 704 to 743 cells/mm3). But there seemed to be some immunological benefit from switching to etravirine, as a significant increase in CD4 cell percentage was observed in the patients switching to this drug (32 to 34%; p = 0.025).

The lipid profiles of patients who continued to take a protease inhibitor remained unchanged. However, median total cholesterol fell from 286 to 186 mg/dl (p = 0.037) for the patients in the etravirine arm, and these individuals also experienced a significant fall in their triglycerides (168 to 107 mg/dl; p = 0.004).

Once-daily dosing of etravirine achieved a trough concentration of 577 ng/ml, well within the therapeutic range, and no patient had a concentration of the drug below 4 ng/ml.

One patient in the etravirine arm voluntarily withdrew from the study, as did two individuals in the control arm. Answers to questionnaires showed that patients were highly satisfied with their switch to etravirine.

“Treatment simplification to once-daily etravirine seems to be safe and effective in HIV-infected patients with virological suppression while receiving protease inhibitor-based antiretroviral treatment,” conclude the investigators. “This strategy permits once-daily dosing and results in improvements in lipid profiles and patient satisfaction while maintaining viral suppression.”

References

Echeverria P et al. Pilot study to assess the efficacy and safety of switching protease inhibitor to once-daily etravirine in HIV-1-infected subjects with viral suppression: Etra-Switch study. 51st Interscience Conference on Antimicrobial Agents and Chemotherapy, abstract H2-785, Chicago, 2011. (Click here for the abstract.)