Diffuse myocardial fibrosis is uncommon in people with perinatally acquired human immunodeficiency virus infection

This is the first study to our knowledge to examine diffuse fibrosis in PLWH on ART, who acquired HIV perinatally. This group is of particular importance to study given three decades of HIV exposure, yet with few traditional CVD risk factors. Using historic controls to compare the prevalence of abnormal myocardial fibrosis, we found no statistically significant difference in ECV fraction between pnHIV group versus those unaffected by HIV.

As a part of CMR analysis in these patients, tissue characterization is performed through myocardial T1 and T2 mapping techniques, ECV calculation, and assessment of LGE by direct visualization. LGE is the gold standard for assessment of non-viable myocardium; however, LGE may not detect diffuse fibrosis due to lack of normal myocardium in extensive disease and limitations of spatial resolution [12]. ECV fraction is a marker of diffuse fibrosis, derived from native T1 values, shortened post-contrast T1 values (following administration of gadolinium-based contrast agents), and hematocrit. ECV provides an estimate of interstitial and extracellular matrix, which increases with ventricular remodeling and collagen deposition in disease states, such as myocarditis. CMR-based fibrosis in chronic HIV infection is well-established in patients that acquired HIV later in life [4].

Fibrosis in PLWH has important prognostic implications, including development of heart failure and death [13, 14]. Outcome studies in PLWH demonstrated higher prevalence of diffuse myocardial fibrosis by CMR in patients who had cardiac events compared to those that did not during short interval follow-up [14]. There was also statistically significant difference in myocardial edema and native T2 values in patients who had events compared to those who did not [14]. In our study, we found no differences in T1 mapping and ECV fraction between the patients with perinatal HIV from controls. Reasons are likely multifactorial and raises the question whether there are intrinsic differences between treated perinatal HIV infection and infection acquired later in life, as it relates to immune regulation, viral replication, antiretroviral exposures, and other mechanisms [15]. In a cross-sectional CMR-based study in South Africa, prolonged exposure to ART in perinatal infection is thought to be cardioprotective, causing less severe left ventricular remodeling, as evidenced by lower mass-to-volume ratio when compared to uninfected controls. No difference in tissue characterization was seen between groups [16]. Another possibility in our cohort is the low overall burden of fibrosis, which could yield non-significant difference in ECV. In a small prospective cohort study, LGE was seen in a majority of patients with HIV compared to controls; however, the overall volume of LGE was low at 3.4%. The authors suggested that the low extent of fibrosis, may also explain why there was nonsignificant difference in ECV fraction [17].

Our patient population with pnHIV is younger by decades than most published studies of PLWH who have undergone CMR to evaluate for fibrosis. Younger patients may lack traditional modifiable risk factors for early CVD, specifically dyslipidemia. In our study population, the prevalence of chronic metabolic conditions known to place patients at increased risk of CVD, such as obesity, diabetes mellitus, and hypertension, was low [17]. In addition, the majority of these patients had never smoked nor had coronary artery disease or myocardial infarction. When CVD risk factors are absent, adults with PLWH are less likely to have diastolic dysfunction by echocardiogram suggesting an important role of traditional CVD risk factors that may work in tandem with HIV to impair cardiac function [18]. While CVD in PLWH is likely related to viral infection, ART administration, and other co-morbidities, younger patients who have not acquired the compounded modifiable risks may lack CMR-based fibrosis.

Early and sustained exposure to ART is also likely to play a role in mitigating cardiac fibrosis. With pnHIV initiation of ART occurs sooner after infection than if infection acquired later life [19, 20]. Longer duration of ART results in less end-organ damage as the result of sustained undetectable viral load [21]. In a prospective study following serial CMR data in treatment naive patients with repeat exam after 9 months on ART, myocardial edema improved as evidenced by a decrease in native T1, T2 values, and ECV fraction [22]. Improvement in tissue composition was associated with a decrease in viral load and CRP, with an increase in CD4 cell count, suggesting that myocardial inflammation and edema are responsive to ART [22]. Improvement in inflammation supports that hypothesis that early initiation of ART in pnHIV improves cardiac tissue characteristics in these patients compared to infection acquired later.

There are several limitations to our study. This was a pilot study in an under-studied population that was limited in sample size. Our study may not have been sufficiently powered to detect difference in ECV, as it was difficult to recruit patients to undergo CMR examination during the COVID-19 epidemic. The patients recruited in our study are also likely to be the most compliant patients. As such, the findings may not be as generalizable to a broader context of PLWH. Our study was also a cross-sectional design, and did not prospectively follow patients longitudinally with serial CMRs to detect subtle changes in pre-contrast T1, LGE or ECV with time.