Potential drug interactions among people with HIV taking statins

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Drug interactions remain a potential problem for HIV-positive people who are treated with statins, according to research. Potential interactions were detected between statins and modern antiretroviral drugs – especially cobicistat – and also medications used to treat other illnesses that are now common in people with HIV.

The research highlights the importance of both care providers and patients checking for potential interactions when starting or changing therapy.

“The proportion of patients with HIV taking contraindicated statins declined between 2007 and 2014, primarily as the result of lower use of protease inhibitors,” write the investigators at the Icahn School of Medicine at Mount Sinai, New York and the University of Alabama at Birmingham. “This decline was partially counteracted by increased use of cobicistat after 2012. As a consequence of the increased use of cobicistat, the proportion of HIV beneficiaries taking contraindicated statins did not continue to decrease through 2015.”

Many older HIV-positive people are now living with multiple illnesses requiring separate medications, complicating care and often involving a risk of drug interactions.

Treatment with statins is a mainstay of the prevention of cardiovascular disease. Statin use is highly prevalent among people with HIV, but several statins have the potential to interact with specific antiretrovirals and other medications routinely taken by people with HIV for conditions such as high blood pressure, elevated blood lipids and infections. The interactions happen because of the way these drugs are processed by the body, potentially increasing concentrations of statins, which could lead to muscle pains and acute kidney damage.

Antiretroviral treatment options have changed significantly over the past decade or so, especially due to the introduction of integrase inhibitors and the boosting agent cobicistat.

With these new antiretrovirals in mind, a team of investigators designed a retrospective study involving over 186,420 Americans who were treated with antiretrovirals between 2007 and 2015. Their aims were to describe trends in statin use, especially the use of statins contraindicated for use with antiretrovirals and other medications commonly taken by people with HIV.

Contraindicated statin use was defined as the prescription of an HIV protease inhibitor, cobicistat, a hepatitis C protease inhibitor, anti-infectives, calcium channel blockers (used to treat high blood pressure), amiodarone (a therapy for irregular heart beat), gemfibrozil (a lipid lowering agent) or nefazodone (an antidepressant), followed by prescription of a type or dose of a contraindicated statin within 90 days.

Over 80% of participants were male, and the proportion aged 60 years and older increased from 9% in 2007 to 16% in 2015. There was a steadying increase in the proportion of people diagnosed with coronary heart disease (3.2% in 2007; 3.9% in 2015), hypertension (31% in 2007; 36% in 2015), diabetes mellitus (3.4% in 2007; 6.7% in 2015) and chronic kidney disease (2.8% in 2007; 5.9% in 2015).

Patterns of antiretroviral prescribing changed significantly over the study period, with the proportion of people taking a protease inhibitor falling from 51% in 2007 to 26% in 2015. The use of cobicistat increased from 0% before 2012 (the year of its approval) to 16% in 2015, and the use of integrase inhibitors increased from 2% to 36% over the eight years of the study.

In each year, the most commonly used non-HIV medications with the potential to interact with a statin were calcium channel blockers (7.0%-9.5%), antifungals (5.0%-7.6%) and antibiotics (2.3%-4.8%). These findings are suggestive of the large numbers of separate medications that HIV-positive people are now taking to treat multiple long-term health conditions.

Despite the ageing of the study population and the increased prevalence of cardiovascular risk factors, prevalence of statin use between 2007 and 2015 remained stable at around 25%. The most commonly prescribed statins were atorvastatin, pravastatin and rosuvastatin.

Analysis of people treated with a statin showed that the proportion taking a contraindicated medication declined from 16.3% in 2007 to 9.0% in 2014. This fall was primarily due to decreased use of HIV protease inhibitors, which accounted for 64% of all contraindicated use in 2007 and 51% in 2015.

But prevalence of contraindicated statin use slightly increased to 9.8% in 2015. This was primarily due to increased use of cobicistat, which accounted for 21% of all contraindicated use in 2015.

Risk factors for contraindicated statin use included older age, male sex, hypertension and diabetes. This may reflect high statin doses given to individuals at higher risk of cardiovascular disease.

“Patients with HIV taking cobicistat who initiate statin therapy should be prescribed atorvastatin or rosuvastatin (statins with the lowest risk of interacting) at the lowest dosages and these medications should be titrated with close monitoring for adverse reactions,” recommend the authors.

They also suggest that alternatives to calcium channels blockers should be sought for people with HIV taking statins who require therapy for high blood pressure. Similarly, HIV-positive people with high triglycerides should receive fenofibrate and omega-3 fatty acids in preference to gemfibrozil, which was used in up to 5% of people.

“The current study supports the need to increase the appropriate use of statins among people living with HIV,” conclude the investigators. “Clinicians should be vigilant in prescribing statin types and dosages with no or minimal contraindications among adults living with HIV.”

The research also shows why it is important for people who are taking multiple medications to inform their healthcare providers – HIV doctors, other specialists, GPs and pharmacists – about all the medications they are taking when they are offered or prescribed a new treatment.

Abstract
Background: HIV is associated with an increased risk for atherosclerotic cardiovascular disease, which may result in many people living with HIV taking a statin. Some statins are contraindicated with certain antiretroviral therapies (ART) and other medications commonly used by HIV‐infected patients.
Methods and Results: We analyzed trends in the use of statins, including contraindicated statins, between 2007 and 2015 among HIV‐infected patients aged ≥19 years taking ART who had employer‐sponsored or Medicare supplemental health insurance in the Marketscan database (n=186 420). Statin use was identified using pharmacy claims. Contraindicated statin use was defined by a pharmacy claim for HIV protease inhibitors, cobicistat, hepatitis C protease inhibitors, anti‐infectives, calcium channel blockers, amiodarone, gemfibrozil, or nefazodone followed by a fill for a contraindicated statin type and dosage within 90 days. The percentage of beneficiaries with HIV taking a statin remained unchanged between 2007 (24.6%) and 2015 (24.7%). Among those taking a statin, the percentage taking a contraindicated statin declined from 16.3% in 2007 to 9.0% in 2014 and then increased to 9.8% in 2015. The proportion of contraindicated statin fills attributable to HIV protease inhibitors declined from 63.9% in 2007 to 51.0% in 2015, while those attributable to cobicistat increased from 0% before 2012 to 20.6% in 2015.
Conclusions: Changes in ART regimens resulted in a decline in contraindicated statin use from 2007 to 2014, but this favorable trend was attenuated in 2015 because of increased use of cobicistat‐containing ART regimens.

Authors
Robert S Rosenson, Lisandro D Colantonio, Greer A Burkholder, Ligong Chen, Paul Muntner

Aidsmap material
Journal of the American Heart Association abstract


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