Combined antiretroviral therapy with low- or normal-protein, high-calorie diets appears to induce significant deleterious electrocardiographic changes in a rodent model.
This study examined how combination antiretroviral therapy (cART) interacts with calorie-dense diets to affect heart function in a rat model. One hundred and twenty weanling Sprague Dawley rats were assigned to one of three diets (normal chow, calorie-dense low-protein, or calorie-dense normal-protein) for 15 weeks, then subdivided into four treatment groups for an additional 9 weeks: saline control, dolutegravir (DTG) plus tesamorelin, DTG alone, or a classical cART regimen. At week 24, electrocardiographic (ECG) recordings and myocardial tissue analysis were performed. The study found statistically significant differences across groups in multiple ECG parameters, including Q, R, S, and T wave amplitudes, PR interval, QRS duration, ST height, and corrected QT interval. Myocardial fibrosis was notably observed in animals receiving DTG alone or classical cART while on calorie-dense diets. The authors suggest these structural changes may disrupt electrical conduction and predispose to arrhythmias. Notably, tesamorelin appeared to attenuate these cardiac effects, leading the authors to implicate growth hormone pathway dysfunction in the pathology. Key limitations include the exclusive use of an animal model, meaning findings may not directly translate to humans.
Why this grade: The study was conducted entirely in Sprague Dawley rats with no human participants, so its findings cannot be directly extrapolated to clinical outcomes in people living with HIV.
The introduction of combination antiretroviral therapy (cART) has significantly reduced AIDS-related morbidity and mortality. However, the prevalence of age-associated comorbidities, particularly cardiovascular diseases (CVD), has increased, becoming a leading cause of mortality in people living with HIV. This study investigated the interaction between cART regimens and dietary composition on electrocardiographic (ECG) parameters and myocardial histopathology. A total of 120 weanling Sprague Dawley rats were allocated to one of three diets for 15 weeks: normal chow, a calorie-dense low protein (CDLP) diet, or a calorie-dense normal protein (CDNP) diet. Each dietary group was then subdivided into four treatment groups for a further 9 weeks: a standard group (normal saline), Test group 1 (dolutegravir (DTG) plus tesamorelin), Test group 2 (DTG only), and a positive control (classical cART regimen). ECG recordings and histological assessments were performed at week 24. Significant intergroup variations in ECG indices were observed, including Q, R, S, and T wave amplitudes, PR interval, QRS duration, ST height, and QTc (all P<0.0001). Myocardial fibrosis (P<0.0001) was evident in animals from the TG2 (DTG only) and PC (classical regimen) groups maintained on CDLP and CDNP diets. These findings demonstrated that CDLP and CDNP diets, combined with DTG-based or classical cART regimens, exerted deleterious cardiac effects, promoting myocardial fibrosis that disrupts normal electrical conduction and may predispose to arrhythmogenesis. Tesamorelin prevented these effects, implicating growth hormone pathway dysfunction in the underlying pathology.
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