Discussion

Reports describing severe toxicity following EVG/COBI/FTC/TAF overdose remain limited [2]. Most previously reported overdoses have demonstrated relatively mild clinical courses managed with supportive care alone. In contrast, this patient developed shock requiring vasopressor support, acute hypoxic respiratory failure, metabolic acidosis, QTc prolongation, acute kidney injury, and reduced systolic cardiac function requiring ICU-level management. The fixed-dose composition of EVG/COBI/FTC/TAF complicates causal attribution because its components have distinct pharmacologic roles: elvitegravir is an integrase strand transfer inhibitor, cobicistat is a pharmacokinetic enhancer via CYP3A inhibition, and emtricitabine and tenofovir alafenamide are nucleos(t)ide reverse transcriptase inhibitors [1]. In the absence of quantitative drug concentrations, the relative contribution of each component to this patient’s clinical deterioration cannot be determined. Potential contributors to the observed multisystem toxicity are summarized in Figure 4. Mitochondrial toxicity has been described with nucleos(t)ide reverse transcriptase inhibitors; however, this mechanism could not be confirmed in this case [6].

Figure 4: Potential contributors to delayed multisystem toxicity following large-volume EVG/COBI/FTC/TAF ingestion. This proposed model does not establish causality or identify a specific toxic component.ATP: adenosine triphosphate; QTc: corrected QT interval; LVEF: left ventricular ejection fraction; EVG/COBI/FTC/TAF: elvitegravir, cobicistat, emtricitabine, and tenofovir alafenamide.

Although chronic amphetamine use may have contributed to baseline cardiac vulnerability, the delayed onset of profound hemodynamic instability after ingestion, together with the absence of evidence for an alternative acute etiology, raises concern for overdose-associated toxicity. Prior reports have described delayed metabolic abnormalities and prolonged observation requirements following EVG/COBI/FTC/TAF self-poisoning [2]. Consistent with these reports, our patient initially appeared clinically stable before deteriorating over the following 24 hours. This pattern may support extended observation following large-volume EVG/COBI/FTC/TAF ingestion, even in patients with an initially reassuring presentation.

Cardiac findings included left ventricular dilation and an ejection fraction of 25%-35%. HIV-associated cardiomyopathy and medication-induced stress cardiomyopathy have both been described previously [3-5]. Baseline cardiac imaging was unavailable, limiting definitive attribution of systolic dysfunction to the overdose alone. Respiratory decline was likely multifactorial, including pulmonary edema, volume overload, impaired cardiac function, and systemic toxic effects. Additional reports are needed to better characterize the cardiovascular and systemic manifestations associated with severe EVG/COBI/FTC/TAF overdose.