Acute onset myopericarditis as unusual presentation of primary HIV infection

Introduction

Up to 80% of subjects experiencing a primary HIV infection are either asymptomatic or paucisymptomatic. Signs and symptoms directly referable to HIV infection usually occur 2–6 weeks after exposure to HIV, and the primary infection often presents as a self-limiting mononucleosis-like syndrome. Only in rare cases, cardiac involvement has been associated with an acute, primary HIV infection, as reported by international literature records, which remain limited to seven cases, usually described as anecdotal reports, or as a part of more extensive observational studies devoted to the investigation of the natural history of HIV disease.^1–7

Here we report a case of acute myopericarditis as the initial clinical manifestation of a primary HIV infection, as an alert to physician to maintain an adequate attention to cardiac manifestation even in the first weeks from a suspected or ascertained primary HIV infection.

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Case report

A 30-year-old, caucasian homosexual man with a 7-day non-specific history of hyperpyrexia and sore throat empirically treated with broad spectrum antibiotic therapy, was admitted to hospital after complaining of a retrosternal burning pain, radiating to the jugular region, and to both upper limbs. An electrocardiography (ECG) examination showed a synusal rhythm with a slight ST segment elevation involving the lower-lateral leads. An ischemic damage was carefully excluded by our cardiologists, on the ground of different instrumental and laboratory examination (troponin curve). The same cardiologists did not consider a coronary angiography in their work-up.

A transthoracic ultrasonography made at day 3 showed a minimal mitral regurgitation and a right ventricle hypokinesia, in a comprehensive context compatible with an acute myopericarditis. A heart magnetic resonance imaging (MRI) was obtained at day 5: it confirmed both clinical and ultrasonographic findings of a myocarditis-pericarditis. In the meantime, all performed serological testings excluded other recent infections, including active or latent tuberculosis (by IGRA test, too). Among screening tests scheduled for a myocarditis, a peripheral lymphocyte subset analysis was performed, so that an inversion of the CD4/CD8 ratio was found, with a reduction of the absolute CD4 T-lymphocyte count (391 cells/µL). Therefore, HIV testing was finally performed and proved positive for HIV-1 antibodies, with plasma HIV-RNA levels of 46,701 copies/mL. The genotypic analysis disclosed the presence of HIV-1 wild type R5 tropic strain as master sequence both in plasma and PBMCs. The phylogenetic analysis identified a HIV-1 subtype CRF 24_BF.

The discovery of a primary, symptomatic HIV infection with involvement of a vital organ led us to start immediately a potent antiretroviral therapy, including tenofovir/emtricitabine, and darunarir/ritonavir. On day 20, our patient underwent a right heart catheterization and endomyocardial biopsy, but the procedure was complicated by cardiac tamponade which required an urgent pericardiocentesis and the placement of a pericardial drainage.

During the following days, the clinical conditions of our patient improved rapidly, and a further heart ultrasonography (performed after 19 days) documented a mild pericardial thickening in the absence of pericardial effusion, as a result of the recent myopericarditis. Also the evolving changes of ECG were compatible with a benign evolution of myopericarditis, in absence of any sign of ischemia. Concurrently, a complete re-absorption of the pericardial effusion was achieved during the next weeks.

The patient became fully asymptomatic and was discharged on day 24, with a well-tolerated antiretroviral therapy. Its clinical, laboratory, and instrumental situation remained unchanged until now (40 days after discharge).

The histopathologic studies of the biopsy specimen revealed a mild fibrosis of the myocardial right ventricular tissue, and inflammatory findings compatible with an active myocarditis. The real-time PCR analysis on bioptic sample excluded the presence of EBV, HSV-1/2, HHV8, CMV, PARVO B19, Enterovirus, and Adenovirus.

Only HHV6 DNA was reactive (<10 copies/µg DNA) and HIV-DNA (69 copies/µg). An immunofluorescence staining was performed to highlight the HIV p24 protein and a positive signal was detected in myocardial tissue. Considering the low avidity level of the anti-HIV IgG antibodies (0.5 AI) and the positivity of HIV-DNA in the endomyocardial tissue, we believe that the clinical manifestation presented by our patient in the absence of other causative agents can be referred to the recent primary HIV infection.

Discussion

Heart is a well recognized target for ischemic, opportunistic, neoplastic, and drug-related damage over the 30-year-long natural history of HIV disease, starting with the early description of multiple possible co-factors of heart damage identified before the era of highly active antiretroviral therapy (HAART). ⁸ The same situation occurred in a series from Africa, where the majority of patients did not have access to HAART. ⁹ Also in the pre-HAART era (year 1995), the first case of primary HIV infection presenting as myopericarditis and rhabdomyolisis was reported. ¹

Another anecdotal observation of a simultaneous primary infection with HIV and Cytomegalovirus leading to multiple-organ involvement and including also a perimyocarditis has been published in 1990. ² A lethal non-specific dilated cardiomyopathy was possibly attributed to a primary HIV infection in a case report of 1999. ³ Registry data reported this pathologic association in HIV-infected children too. ⁴ Later, a patient with a concurrent myocarditis and meningoencephalitis as the presentation of primary HIV-1 infection was reported from Spain. ⁵ An unusual, multisystemic presentation of primary HIV infection including a myocarditis was published in 2009 from Spain. ⁶ Finally, in the year 2012, a primary HIV infection induced an acute ventricular fibrillation, but the heart disease was accompanied by a disseminated multiorgan involvement. ⁷ No further reports were published after 2012, with regard to episodes of myocarditis–pericarditis attributed to a primary HIV infection. Moreover, our data include histopathology obtained by right cardiac catheterization, which was burdened by a rare, but self-limiting tamponade. This last complication is reported very infrequently by recent studies performed on large case series (<0.5%). ¹⁰

In our case, a well-documented primary HIV infection characterized by a very recent prior negative HIV serology, and a low antibody avidity index at the first detection of HIV disease (below 0.8), on the ground of an outstanding laboratory in-house assay performed at our University Division of Microbiology, ¹¹ was associated with a severe, potentially life-threatening myocarditis–pericarditis, which luckily went to a spontaneous resolution, probably aided by the concurrent HAART regimen.

In conclusion, an early onset myopericarditis is a possible, although uncommon manifestation of acute HIV infection, while the natural history of HIV disease showed a progressive involvement of cardiovascular system caused by premature aging, HIV infection itself, and several antiretroviral drugs. Our case presentation and the literature search underline the need for a careful cardiologic evaluation in patients with a recent diagnosis of HIV infection, in particular when subjects with thoracic pain or other possible cardiac signs and symptoms are of concern.