Infection

Case Report

Disappearance of an Intracerebral Arteriovenous
Malformation in an HIV-Infected Patient after
Initiation of HAART
K. Wolf, E.C. Kirsch, L. Sponagel, D.A. Rüfenacht, M. Battegay

Abstract
HIV infection or complications of HIV-induced immunodeficiency may affect the central nervous system (CNS). However,
vascular cerebral pathologies are very rare, in particular
intracerebral arteriovenous malformations (AVM). We report
the case of an HIV-infected patient who had a cerebral AVM
leading to symptoms such as recurring focal seizures. Only
after initiation of potent antiretroviral combination therapy,
but not antiretroviral monotherapy or bitherapy, could the
viral load be suppressed and immunodeficiency resolved. Two
years after the start of highly active antiretroviral therapy
(HAART) total occlusion of the AVM could be demonstrated.
Taken together, this case report may demonstrate the potent
angiogenic activity of HIV for AVM. Also, this case report
might show that inhibition of such a cofactor may lead to
resolution of an AVM.

Key Words
HIV · Arteriovenous malformation · Antiretroviral therapy
Infection 2002; 30: 101–103
DOI 10.1007/s15010-002-2100-7

Introduction
HIV infection or complications of immunodeficiency, including infection with opportunistic microorganisms and
malignancies, may affect the CNS [1]. Vascular cerebral
pathologies in HIV-infected patients include arterial fibrosis, calcification, vasculitis and rarely intracerebral arteriovenous malformations (AVM) [2].We report the case of an
HIV-infected patient who had a cerebral AVM which completely resolved 2 years after initiation of potent antiretroviral combination therapy.

Case Report
The 53-year-old patient had acquired HIV infection in 1984. An
oral hairy leukoplakia and a generalized lymphadenophathy were
found and considered as HIV-related diseases. In 1989 he complained of recurrent vertigo, focal seizures with dysesthesia and
weakness of his left leg. On cerebral magnetic resonance imaging
(MRI) no signs of infarction, bleeding, encephalitis or toxoplas-

Infection 30 · 2002 · No. 2 © URBAN & VOGEL

Figure 1. Right internal carotid digital subtraction angiography (lateral plane), before initiating a potent antiretroviral combination
therapy. A rolandic, moderate sized AVM (black arrow) is demonstrated, with arterial supply from the right anterior and middle cerebral arteries. Note the large venous varix (arrowheads), which conducts the venous drainage to the adjacent superior sagittal sinus.

K. Wolf, L. Sponagel, M. Battegay (corresponding author)
Basel Center for HIV Research, Outpatient Dept. of Internal Medicine,
University Hospital Basel, Petersgraben 4, CH-4031 Basel, Switzerland,
Phone: (+41/61) 265-5072, Fax: -4604, e-mail: mbattegay@uhbs.ch
E.C. Kirsch
Neuroradiology, Dept. of Radiology, University Hospital Basel,
Switzerland
D.A. Rüfenacht
Neuroradiology-HUG, University Hospital Geneva, Switzerland
Received: June 15, 2001 • Revision accepted: December 3, 2001

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K. Wolf et al. Intracerebral Arteriovenous Malformation and HIV

Figure 3. Right internal carotid digital subtraction angiography (lateral plane) 2 years after the antiretroviral combination therapy. Disappearance of the AVM (black arrow).
Figure 2. Unenhanced CT on the level of the high frontoparietal region. A hyperintense area, located in the right, parafalcine central
gyrus (white arrow) is demonstrated, consistent with thrombosis of
the former AVM.

mosis were detected. However, a cortical AVM was found in the
right parietal lobe in the parasagittal region. On digital subtraction angiography (DSA) a rolandic, moderate sized (< 3 cm) AVM
was confirmed, with arterial supply from the right anterior and
middle cerebral arteries. There was single venous drainage to the
adjacent superior sagittal sinus with a large varix. Additionally, a
flow-related aneurysm of the pericallosal artery was diagnosed.
After initiation of carbamazepine (400 mg bid), focal seizures recurred only sporadically. HIV infection remained stable for the
next few years with CD4 T-cell counts between 300/µl and 500/µl,
i.e. indicative of an intermediate immunodeficiency. In December
1990 an antiretroviral monotherapy with zidovudine (250 mg
twice a day) was initiated and changed to didanosine (200 mg
twice a day) in July 1991. In November 1996, the frequency of
seizures increased. A repeat brain MRI revealed no changes. On
DSA the right parietal AVM remained patent and was unchanged
in size (Figure 1). Importantly, the viral load was never suppressed
due to insufficient monotherapy. In July 1997 a potent antiretroviral combination therapy containing stavudine (40 mg twice a
day), lamivudine (150 mg twice a day) and indinavir (800 mg three
times a day) was started. Viral loads were suppressed for the first
time below the limit of detection of 20 copies/ml. For HIV quantification plasma samples were processed according to the published protocols of the Roche HIV monitor test kit (Roche Diagnostics, Rotkreuz, Switzerland), with the modification of the ultrasensitive assay [3]. Subsequently, CD4 T-cell counts rose significantly to above 500/µl. In summer 1999, the patient suffered
again from recurrent focal seizures to his left leg. The AVM was
demonstrated to trigger these seizures on electroencephalography. In November 1999, the patient was hospitalized for a generalized tonic-clonic seizure. On unenhanced computed tomogra-

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phy (CT) a hyperintense lesion was seen in the region of the earlier AVM, suspicious for a spontaneous thrombosis (Figure 2).
This was confirmed with cerebral DSA.The AVM had undergone
substantial changes without evidence for arteriovenous shunting.
In addition, feeding arteries were reduced in size and venous
structures only mildly increased (Figure 3). For persistence of sensible Jackson seizures, an antiepileptic therapy with oxcarbazepine (600 mg twice a day) was started. In June 2000, a followup MRI of the neurocranium showed a progressive organization
and resorption of the parietal thrombosis. On follow-up MR angiography and cerebral DSA examinations a total occlusion of
the AVM with normalization of the locoregional brain vasculature could be demonstrated at 1.5 years after diagnosis of thrombosis. The patient is clinically well and remains under anti-epileptic and anti-HIV medication. Electroencephalography in June
2000 showed a marginal change in normal activity, probably due
to anti-epileptic therapy. However, no focus and no sign of cerebral hyperexcitability could be detected. The efficacy of antiretroviral therapy is still excellent with a suppressed viral load
and a CD4 T-cell count of 616/µl.

Discussion
An intracerebral AVM is uncommon during HIV infection.
Most case reports of AVM in HIV-infected patients concern children [4–7]. Interestingly, in these patients viral activity was usually very high, or the stage of HIV disease advanced [4]. In one study, HIV antigen was demonstrated in
cells of the intima of an aneurysm of the circle of Willis of
a 6-year-old boy [5], supporting a possible association of
HIV and AMV. Significant angiogenic potential of virus
could be demonstrated in HIV-infected patients coinfected
with human herpesvirus 8, who developed Kaposi’s sarcoma [8]. The molecular pathogenesis is being elucidated

Infection 30 · 2002 · No. 2 © URBAN & VOGEL

K. Wolf et al. Intracerebral Arteriovenous Malformation and HIV

by recent findings, e.g. the potent trans-activator HIV protein Tat and its short core domain, Tat21-40, possesses potent angiogenic activity [9]. Tat also augments the activities of angiogenic molecules, such as basic fibroblast
growth factor, interferon gamma and vascular endothelial
growth factor [10]. Taken together, these results may
demonstrate a role of HIV in activating an AVM. Conversely, potent antiretroviral therapy may reduce the activity of the virus-driven angiogenic process and subsequently lead to thrombosis of the AVM and its resolution
as observed in our patient. First clinical signs of AVM 5
years after HIV diagnosis with active viral replication and
resolution 2 years after initiation of potent anti-HIV therapy may argue for our hypothesis. On the other hand, very
few spontaneous disappearances of AVM are reported
[11–15]. Thrombosis within the vessels of an AVM is believed to be the most frequent cause.This may be triggered
by intracerebral hemorrhage secondary to AVM rupture
[12], due to accompanying brain edema and vasospasm
[11], occlusion of a single draining vein with consecutive
venous outflow obstruction and lesion thrombosis [13] or
due to head injury [15]. Interestingly, immunohistochemical analysis of a thrombosed AVM revealed ongoing active
angiogenic changes within AVM vessels 1 month after
thrombosis [13]. This might suggest the possibility that
viruses are significant cofactors for angiogenic processes
and activation of AVM.The patient described in our report
highlights an uncommon but clinically relevant and potentially life-threatening pathology in HIV-infected patients. Options for treatment of a cerebral AVM generally
include watchful waiting, endovascular embolization,
surgery and radiosurgery. Although it is not possible to
construct a definite causal relationship upon a single case
report, potent antiretroviral therapy may offer an additional therapy option in HIV-infected patients presenting
with an AVM via inhibition of virus-induced angiogenic
stimulation.

Acknowledgments
The authors are thankful to Edouard Battegay and Ernst-Wilhelm
Radü for valuable discussions.

Infection 30 · 2002 · No. 2 © URBAN & VOGEL

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