Drug interactions remain a potential problem for HIV-positive people who are treated with statins, according to research published in the December issue of the Journal of the American Heart Association. 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. “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.
Visit the University of Liverpool's HIV Drug Interactions website to check possible drug interactions.
Rosenson RS et al. Trends in utilization of statin therapy and contraindicated statin use in HIV-infected adults treated with antiretroviral therapy from 2007 through 2015. Journal of the American Heart Association 7:e010345, 2018. (Full text freely available.)