Once-a-day treatment: the consequences of poor adherence may be more serious

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Although once-a-day treatment regimes can be expected to make adherence easier to handle, if a person does miss doses, the clinical consequences are more serious than if a person misses doses from a twice-a-day regime. Tracy Glass reported these findings from the Swiss HIV Cohort at the Fifth International Conference on HIV Treatment Adherence in Miami on Monday.

Much effort has been taken in recent years to make antiretroviral therapy more tolerable and easier to take, in particular the development of once-daily therapy. Treatment regimes involving fewer doses are generally easier for people to adhere to.

Patients starting HIV therapy for the first time in Switzerland were recruited to the study between 2003 and 2009. Adherence was measured by self-report of missed doses over the last month. The investigators assessed the association of missed doses with viral rebound and death.

Glossary

viral rebound

When a person on antiretroviral therapy (ART) has persistent, detectable levels of HIV in the blood after a period of undetectable levels. Causes of viral rebound can include drug resistance, poor adherence to an HIV treatment regimen or interrupting treatment.

tolerability

Term used to indicate how well a particular drug is tolerated when taken by people at the usual dosage. Good tolerability means that drug side-effects do not cause people to stop using the drug.

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.

hazard

Expresses the risk that, during one very short moment in time, a person will experience an event, given that they have not already done so.

nucleoside

A precursor to a building block of DNA or RNA. Nucleosides must be chemically changed into nucleotides before they can be used to make DNA or RNA. 

A total of 2410 individuals were recruited to the study and were followed for a median of 2.7 years.

At approximately one-third (30%) of interviews, patients reported missing one or more dose of their antiretroviral therapy. Viral load rebounded to detectable levels in 8% of patients, and 3% of individuals died.

For patients taking once-daily treatment, missing any doses increased the risk of viral load rebounding. The risk increased with the number of doses missed (one dose missed, hazard ratio (HR) = 5.46; 95% CI, 1.69 to 17.67; two missed doses, HR = 6.87; 95% CI, 1.07 to 44.01; three or more missed doses, HR = 9.26; 95% CI, 2.26 to 37.99).

Moreover, patients taking their HIV treatment once a day who reported missing three or more doses had a significantly increased risk of death (HR = 2.90; 95% CI, 1.09 to 7.72).

On the other hand, missed doses did not have such serious consequences for patients taking twice-daily therapy. No statistically significant relationship was found between missed doses and either an increased risk of viral load, or an increased risk of death.

However during questions and answers, an audience member requested further information on the once-a-day regimes being taken. He suggested that it was possible that doctors were prescribing drugs which are optimally taken twice a day, but which are sometimes prescribed as once-a-day to people who request a simpler regimen. The problem is that these particular drugs are not active in the body for long enough to allow for lapses in adherence.

While the researcher could not clarify the nature of these regimes, she did confirm that the data were also analysed to see if the risk of these events varied according to whether the treatment regime featured a non nucleoside reverse transcriptase inhibitor, boosted protease inhibitor or unboosted protease inhibitor. No variation was found.

Concluding, Tracy Glass said she believed that missed doses on a twice-a-day regimen do not lead to clinical consequences as serious as those created by missed doses on a once-a-day regimen. She cautioned that once-a-day regimens are not necessarily best for all patients.

References

Glass T et al. Are once daily regimens really the magic bullet? Fifth International Conference on HIV Treatment Adherence, abstract 62223, Miami, 2010.