CARDIOVASCULAR JOURNAL OF AFRICA • Vol 24, No 6, July 2013
AFRICA
199
Editorial
Cardiotropic viral infection in HIV-associated
cardiomyopathy: pathogen or innocent bystander?
LORI A BLAUWET, LESLIE T COOPER
Clinical cardiovascular presentations associated with HIV
infectionincludemyocarditis,pericarditis,dilatedcardiomyopathy
(DCM), arrhythmias and vascular disease. The incidence of
cardiomyopathy, myocarditis and pericardial diseases correlates
with the severity of HIV infection as measured by low CD
4
count
or high viral titre. In retrospective series and autopsy studies
performed in the pre-HAART (highly active antiretroviral
therapy) era, the incidence of cardiac involvement in patients
with HIV ranged from 6–79%.
1-6
In areas where HAART is
readily available, the incidence of primary cardiomyopathy in
HIV-infected patients is decreasing, but the prevalence of all
cardiac disease, including atherosclerosis, in these patients is
increasing due to improved survival rates.
Myocarditis with lymphocytic infiltration has been reported
to be present in 40–52% of patients who died of AIDS in the
pre-HAART era.
4
In countries where HAART has been readily
available for a number of years, the prevalence of HIV-associated
cardiomyopathy has been reduced by approximately 30% due
to the prevention of opportunistic infections and a reduction
in the incidence of myocarditis.
7
However, in developing
countries where HAART is not readily available and nutritional
and environmental factors may have a greater impact on the
pathogenesis of cardiac disease, the prevalence of HIV-associated
cardiomyopathy is increasing.
6
Many HIV-infected patients who
do not receive HAART develop cardiac disease.
8
The pathogenesis of HIV-associated cardiomyopathy is
complicated by infection with pathogens that are associated
with immunosuppression, nutritional deficiencies and other
confounding factors. Although the mechanisms by which HIV
infection is associated with cardiac dysfunction remain unclear,
activation of cytokines and alteration of immune cells that affect
cardiac function likely play a significant role.
Another potential confounding factor in the current era is
that nucleoside reverse transcriptase inhibitors, a cornerstone
among the HAART medications used to treat HIV/AIDS,
have occasionally been implicated in the pathogenesis of
HIV-associated cardiomyopathy, possibly through mitochondrial
DNA toxicity.
9,10
In this issue of the
Cardiovascular Journal of Africa
,
Shaboodien
et al
. (page 218) report on associations between
myocarditis, viral infection and HIV-associated cardiomyopathy.
Endomyocardial biopsy specimens of 33 patients (14 with
HIV-associated cardiomyopathy, eight with idiopathic DCM
and 11 heart transplant recipients) were examined. Myocarditis
was present in 44% (6/14) of the patients with HIV-associated
cardiomyopathy (three acute and three chronic myocarditis),
25% (2/8) of the patients with DCM (both chronic myocarditis)
and 36% (4/11) of the heart transplant recipients (two acute
and two chronic myocarditis). Cardiotropic viral infection was
present in 90% of the heart transplant recipients and in all of
the HIV-associated cardiomyopathy and DCM cases. Multiple
viruses were present in most cases.
Several features of the study by Shaboodien
et al.
deserve
comment. First of all, the HIV-positive patients in the study had
not received antiretroviral therapy (ART) and their average CD
4
count was only 246 cells mm
3
. Therefore these observations
provide a contemporary and rare window into the pathogenesis
and natural history of HIV-associated cardiomyopathy in patients
who received no antiretroviral therapy.
Second, the distribution of cardiotropic viruses among the
patients in this series differs from that observed in patients in
more developed countries. The most common viruses present
in the HIV-associated cardiomyopathy patients in this study
were Epstein Barr and herpes simplex, while co-infection with
cytomegalovirus or adenovirus is more common in patients with
HIV-associated cardiomyopathy in North America and Europe.
The most common virus detected in DCM patients in the study
cohort was enterovirus, while Parvovirus B19 was among the
least detected. Among patients with chronic DCM studied in
North America and Europe, Parvovirus B19 is one of the most
common viruses currently being detected. The reason(s) for
these geographic differences is uncertain.
The observation that the number of viruses and the
percentage of patients with myocarditis were numerically higher
in the HIV-associated cardiomyopathy cases than in either
heart transplant recipients with a normal ejection fraction
on immunosuppression or patients with idiopathic DCM
on no immunosuppression suggests that both the state of
immunosuppression and the degree of damage to the left
ventricle contribute to inflammation and cardiotropic viral
infection in the HIV-infected population. Damaged myocardium
from either direct HIV infection or co-infection with other
viruses may provide a ‘danger signal’ to the immune system,
triggering pro-inflammatory cytokine release through toll-like
receptor activation by endogenous antigens such as cardiac
myosin.
HIV-infected patients with advanced cardiomyopathy
represent a high-risk cohort which may potentially benefit from
both additional antiretroviral treatment and tailored therapy
directed specifically at opportunistic viral infection, including
immunisation and/or antiviral drug therapy. The results of the
Shaboodien study are intriguing because they open the possibility
for novel tailored therapy in patients with HIV-associated
cardiomyopathy based on the results of endomyocardial biopsy.
