Decisions Regarding Antiretroviral Drug Therapy in PWH With an Increased Risk of Cardiovascular Disease

Prevention of cardiovascular disease (CVD) in people with HIV (PWH) should be intensified when the underlying risk of CVD is high. European AIDS Clinical Society guidelines recommend determining the underlying CVD risk annually in any male PWH older than 40 years of age and any female PWH older than 50 years. Patient modifiable risk factors such as smoking may exacerbate CVD risk. Obesity also is associated with excess risk of diabetes, hypertension, and dyslipidemia. By modifying factors that may be within the patient’s control, the underlying risk of CVD can be reduced substantially.

Removing or Replacing Medicines Associated With CVD Risk
As prescribers, we can either add or replace medicine to reduce the underlying CVD risk. Medicines that reduce CVD risk include statins, antihypertensives, and diabetic medication, and the indication for the use of these medicines in PWH is similar to the use in the general population. Current HIV guidelines also provide detailed information on possible drug‒drug interactions with HIV medicines.

Antiretrovirals (ARVs) and CVD Risk
Although studies have shown that contemporary HIV medicines do not directly increase the risk of hypertension or diabetes, we still can remove or replace medicines associated with CVD if such modifications do not adversely affect other conditions. For antiretroviral therapy (ART), the 2 contemporaneously used drugs are abacavir (ABC) or boosted darunavir (DRV). Current guidelines recommend avoiding ABC and boosted DRV in patients with elevated risk of CVD, provided that the patient can be switched to other ARVs.

However, the strength of evidence associating certain ARVs with an increased CVD risk is growing.

• An observational study by Sabin and colleagues found a consistent association between the use of ABC and the risk of myocardial infarction. An independent cohort study presented at the 2021 European AIDS Conference by Jaschinski and colleagues showed that 1 in 200 people receiving ABC each year suffered a heart attack, stroke, or other serious cardiovascular event, regardless of whether the patient was at low or high risk of CVD.
• Ryom and colleagues also showed that boosted DRV, but not boosted atazanavir, used over a 5-year period was associated with an increase of CVD of approximately 60%.
• In addition, the TANGO trial demonstrated that lipid levels decreased markedly among patients receiving a suppressive boosted tenofovir alafenamide (TAF)‒containing ART regimen if patients were switched to a simplified regimen of dolutegravir (DTG) and lamivudine. However, a 2-drug regimen may not be ideal for all patients, and adding a third drug in these situations is usually a choice between TAF or tenofovir disoproxil fumarate (TDF).
• Bansi-Matharu and colleagues recently showed that DTG and TAF, but not TDF, is associated with weight gain in the RESPOND cohort (N = 14,703). Whether this weight increase relates to obesity-related CVD-adverse metabolic perturbations, which may then translate to an elevated CVD risk, remains to be clarified and is currently the focus of intense study. If in doubt, I use TDF and monitor kidney function.

Your Thoughts?
How often does CVD risk influence ART selection for your patients? Join the discussion by posting a comment.