Drug interactions still common and often unrecognised in patients taking HIV treatment

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Clinically significant drug interactions are common amongst patients taking antiretroviral therapy, and often are not noticed by HIV doctors, UK investigators report in the May 15th edition of Clinical Infectious Diseases.

Researchers from Liverpool recorded clinically significant drug interactions in 27% of patients, and over a third of these were not noticed by doctors.

“Clinically significant drug interactions involving antiretrovirals are common…and their recognition is necessary for safe and effective prescribing practice,” comment the investigators.

Glossary

multivariate analysis

An extension of multivariable analysis that is used to model two or more outcomes at the same time.

therapeutic drug monitoring (TDM)

The measurement of plasma drug concentrations in an effort to provide the most effective dosage with the least possible side-effects; TDM can help guide decisions regarding changes in drug dosing.

drug interaction

A risky combination of drugs, when drug A interferes with the functioning of drug B. Blood levels of the drug may be lowered or raised, potentially interfering with effectiveness or making side-effects worse. Also known as a drug-drug interaction.

antibiotics

Antibiotics, also known as antibacterials, are medications that destroy or slow down the growth of bacteria. They are used to treat diseases caused by bacteria.

Many antiretroviral drugs can interact with both other anti-HIV drugs as well as medicines used to treat other conditions.

Unrecognised interactions can have serious consequences, resulting in inadequate drug levels to maintain control of HIV, or excess drug levels leading to side-effects.

Although it is recognised that clinically significant drug interactions are common amongst patients taking HIV treatment, no previous study has assessed the extent to which they are recognised by doctors.

Therefore investigators from the Royal Liverpool University Hospital collected data on potentially serious drug interactions seen amongst patients attending the hospital’s HIV clinic in the summer of 2008.

To be included in the study, patients had to be taking at least one antiretroviral drug.

A structured questionnaire was completed by the treating physician. They were asked to record the anti-HIV drugs being taken by the patient, and all other medicines and drugs being used by the individual. This included those prescribed by a healthcare professional, those bought over the counter, and recreational drugs. The treating physician was then asked to identify all potentially significant drug interactions, and to state if they had modified dosage or used therapeutic drug monitoring.

Information was also obtained on the patients’ demographics, and their viral load.

A total of 159 patients were included in the study. Their median age was 41 years and 56% were men. Viral load was undetectable (below 40 copies/ml) in 66% of patients.

Potentially significant interactions were identified in 43 patients (27%).

The investigators’ initial analysis showed that men (p = 0.029), white patients (p = 0.043), and those taking a protease inhibitor (p < 0.001) had the greatest risk of interactions.

In multivariate analysis, the association with protease inhibitor therapy remained highly significant (OR = 10.59; 95% CI, 2.86 to 31.87, p < 0.001). The investigators commented that this finding was “unsurprising”.

Male sex also remained significantly associated with a greater risk of interactions (OR = 3.03; 95% CI, 1.06 to 8.58, p = 0.038). However, the investigators recommended that this finding should be treated with caution. They noted that it lacked “biological plausibility” and has not been identified as a risk factor in any other research.

The recorded drug interactions could have resulted in reduced levels of antiretroviral drugs in 15% of patients.

Only 36% of interactions were correctly indentified by the treating physicians.

A broad range of interactions were observed, including those with other antiretroviral drugs, antidepressants, antibiotics, statins and recreational drugs.

Therapeutic drug monitoring was used to manage 26% of the patients with interactions. Patients who received such monitoring were significantly more likely to have the dosage of their medication altered than patients who did not (OR = 3.25; 95% CI, 1.16 to 9.16, p = 0.015).

The investigators conclude: “We recommend that all physicians are vigilant to the risks of clinically significant drug interactions, use available drug information resources, and that the pharmacy department aid in identification of clinically significant drug interactions and regularly audit prescribing practice.”

References

Evans-Jones JG et al. Recognition of risk of clinically significant drug interactions among HIV-infected patients receiving antiretroviral therapy. Clin Infect Dis 50: 1419-21, 2010.