Cocaine Use in Patients Taking Lenacapavir for HIV
Cocaine use poses significant cardiovascular risks in HIV-infected patients, and while no specific drug-drug interaction exists between cocaine and lenacapavir, the combination of long-term cocaine use with antiretroviral therapy substantially increases the risk of silent coronary artery disease and cardiovascular complications.
Primary Cardiovascular Concerns
Cocaine-Specific Risks in HIV Patients
Long-term cocaine use (≥15 years) is independently associated with a 7.75-fold increased risk of significant coronary stenosis (≥50%) in HIV-infected individuals, representing a much higher risk magnitude than antiretroviral therapy alone 1
Among HIV-infected African Americans who used cocaine long-term and received antiretroviral therapy for ≥6 months, the prevalence of significant coronary stenosis reached 42%, compared to much lower rates in those without these combined exposures 1
Animal research supports that cocaine may have an additive effect with HIV infection in developing pulmonary arteriopathy, suggesting cocaine can potentiate HIV-related vascular complications 2
Antiretroviral Therapy Contribution
Antiretroviral therapy exposure for ≥6 months is independently associated with a 4.35-fold increased risk of significant coronary stenosis, though this risk is substantially lower than the risk from long-term cocaine use 1
The combined effect of long-term cocaine use plus antiretroviral therapy creates a multiplicative cardiovascular risk that far exceeds either factor alone 1
Lenacapavir-Specific Considerations
No Direct Drug Interaction
Lenacapavir is metabolized by CYP3A and UGT1A1, and is a moderate inhibitor of CYP3A with weak P-glycoprotein inhibition 3
Cocaine is not metabolized through pathways that would create a direct pharmacokinetic interaction with lenacapavir, so no dose adjustment of lenacapavir is required 3
Monitoring Requirements for Lenacapavir Patients
Standard lenacapavir monitoring includes liver enzyme tests every 6 months, which becomes particularly important in cocaine users who may have hepatotoxicity risk 4, 5
Injection site reactions occur in 63% of lenacapavir recipients and are typically mild to moderate, but cocaine-induced vasoconstriction could theoretically affect subcutaneous absorption or increase local tissue complications 6
Clinical Management Algorithm
Cardiovascular Risk Assessment
Perform cardiovascular screening in all HIV patients with cocaine use history, particularly those with ≥15 years of use, even if asymptomatic 1
Assess for traditional cardiovascular risk factors (hypertension, hyperlipidemia, smoking, diabetes) as these compound the risk from cocaine and antiretroviral therapy 1
Consider computed tomography coronary angiography for patients with long-term cocaine use on antiretroviral therapy, as silent coronary disease is highly prevalent 1
Harm Reduction Approach
Aggressive cardiovascular risk factor modification is essential, including blood pressure control, lipid management, smoking cessation, and diabetes control 1
Develop and implement cocaine cessation programs, as the cardiovascular risk from cocaine far exceeds the risk from antiretroviral therapy itself 1
Continue lenacapavir as prescribed, since virologic suppression remains the priority for HIV outcomes and there is no contraindication to lenacapavir use in cocaine users 2, 6
Adherence Considerations
Lenacapavir's twice-yearly subcutaneous dosing (every 26 weeks) may be particularly advantageous for patients with substance use disorders who struggle with daily oral medication adherence 2, 5
The initial oral loading doses (600 mg on days 1 and 2) must still be completed to achieve adequate drug levels before the first injection 5
Intensive case management and adherence support for any companion antiretrovirals is critical, as lenacapavir should be used with at least one or two additional fully active agents 7
Critical Pitfalls to Avoid
Do not withhold effective antiretroviral therapy including lenacapavir due to cocaine use, as untreated HIV poses greater mortality risk than the cardiovascular complications from antiretroviral therapy 2, 1
Do not assume patients are asymptomatic for cardiovascular disease based on lack of chest pain complaints, as silent coronary stenosis is common in this population 1
Do not overlook the need for substance use disorder treatment referrals, as cocaine cessation provides the greatest cardiovascular risk reduction 1
Avoid complacency about cardiovascular monitoring simply because lenacapavir has no direct interaction with cocaine—the indirect cardiovascular risks from the combination of HIV, antiretroviral therapy, and cocaine remain substantial 2, 1