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Drug-Drug Interactions
ART in Older Patients: How I Manage Drug–Drug Interactions With Concomitant Medications

Released: October 20, 2015

Expiration: October 18, 2016

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Due to the success of ART, increasing numbers of patients with HIV infection are older than 50 years of age. In addition, it is estimated that worldwide 120,000 people aged 50 years and older acquire HIV each year. As people age, they experience changes in renal function and more frequently develop conditions such as bone mineral density loss, cardiovascular disease, diabetes, and malignancies, all of which will affect the choice of first-line ART.

Safety, Tolerability First
What are the important issues to consider when choosing initial therapy for an older patient? In my opinion, safety and tolerability top the list, as all regimens classified as “recommended” by national and international guidelines are highly effective and capable of achieving undetectable HIV-1 RNA. To this end, I consider all concomitant medications patients are receiving, as many can become unsafe and/or intolerable when coadministered with certain antiretroviral regimens. In one study of HIV-infected patients older than 60 years of age, 70% of participants were receiving at least 1 pair of medications with a potential for drug–drug interactions. These data highlight the need for very close communication between patients, family doctors, other specialists, and the physician managing their HIV disease.

Pharmacoenhancers
The most important antiretrovirals to evaluate for drug–drug interactions are the pharmacoenhancers ritonavir and cobicistat. These agents may affect the pharmacologic levels of many commonly used therapies, such as statins, cardiovascular drugs, CNS agents, antidepressants, anticonvulsants, and fluorinated corticosteroids. Drug interactions with pharmacoenhancers are a major issue in patients who develop malignancy, as they may potentiate chemotherapy drug levels. Given the possible toxicity in bone marrow, kidneys, and liver, I will start or switch patients to an unboosted integrase inhibitor–based regimen if they require chemotherapy.

Tenofovir DF can have adverse effects on both bone and renal health and the use of this drug with others that affect renal function such as NSAIDs requires careful monitoring of eGFR. Based on recent data, I am hopeful that tenofovir AF will offer an improved safety profile once licensed.

Common Comorbidities in Older Patients
As patients with HIV infection grow older, cardiovascular disease becomes an important comorbidity, partly because of effects of the virus as well as a high prevalence of risk factors related to current or previous lifestyle among individuals infected with HIV. Again, drug–drug interactions are important in this setting. In particular, several ART agents can cause increases in calcium channel blockers, and several of the commonly used statins are best avoided in patients receiving pharmacoenhancers. For patients with cardiovascular disease, I favor unboosted integrase inhibitor–based regimens, which have the fewest drug–drug interactions. In addition, interactions between NNRTIs and cardiovascular medications are typically manageable. Like many physicians, I avoid abacavir in patients receiving cardiac drugs due to the unresolved question of its potential link to cardiovascular risk.

Because the incidence of diabetes increases with age, it is important to realize that coadministration of metformin and dolutegravir leads to increased exposure to metformin. Dose modification of metformin may be necessary in this setting.

ART regimens require careful planning in women who are perimenopausal and postmenopausal, in whom bone mineral density loss is an important issue. Moreover, drug–drug interactions with hormonal replacement therapies are an important concern. Here again, I prefer unboosted integrase inhibitors or rilpivirine, which can be used without dose modification of hormonal replacement therapies.

The incidence of neurocognitive disorders also increases as patients age. Efavirenz is best avoided in this setting, as it may cause dizziness, especially if patients wake at night. Although it has not been formally studied, there may be some utility of single-tablet regimens for patients who are developing dementia, due to the ease of use.

In summary, there is no one perfect regimen for the aging patient receiving multiple medications whose physiology is changing and who may have progressive conditions. Regarding the choice of nucleoside/nucleotide backbone, we must weigh the potential risk of cardiovascular events with abacavir against the risk of bone and renal issues with tenofovir DF. In my practice, the third agent is most commonly an unboosted integrase inhibitor due to the favorable tolerability and drug interaction profile of this class. Whatever the final choice, it is wise to thoroughly consider potential drug–drug interactions.

Your Thoughts?
How do you manage drug–drug interactions in older patients receiving ART and multiple concomitant medications? I encourage readers to post their thoughts in the comments section below.

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Approximately what percentage of your patients with HIV is 50 years of age or older?
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