Acute inflammatory demyelinating polyneuropathy following interruption of antiretroviral treatment and HIV rebound Free

Sir,

We present the case of a man diagnosed with HIV-1 infection in 2004. His nadir CD4 T cell count was 14 cells/mm³ (4%) and his baseline plasma viral load was 462 609 copies/mL. He had no history of opportunistic infections. Viral suppression had been maintained since 2005 and the patient had remained stable on ART since 2013. His most recent blood results (2 months prior to admission) showed undetectable viral load and a CD4 T cell count of 1373 cells/mm³.

He presented at the emergency department with a 1 week history of bilateral lower limb paraesthesia in the typical glove-and-stocking pattern, rapidly progressing motor weakness and abnormal gait. No other symptoms were reported. No vaccines had been administered recently. The patient reported he had interrupted ART approximately 45 days before the onset of symptoms.

Physical examination revealed slight dysarthria and mild distal tetraparesis. Upper and lower limb reflexes were abolished and hypoaesthesia in the glove-and-stocking pattern was recorded. No other remarkable neurological signs were observed. Full blood count and biochemistry were normal at baseline. A brain CT scan and brain and cervical-dorsal-lumbar MRI showed no abnormalities. CSF examination revealed the following: white cell count of 33 cells (95% lymphocytes); protein, 92 mg/dL; and glucose, 2.2 mmol/L. Gram stain and culture of CSF were negative, as was detection of neurotropic viruses in CSF using RT–PCR. HIV-1 RNA in CSF and blood plasma were 939 copies/mL and 31 207 copies/mL respectively. The CD4 T cell count was 700 cells/mm³.

The results of serology testing for Treponema pallidum, HBV, HCV and Borrelia were negative, as were stool cultures. There was no evidence of Campylobacter jejuni infection. The results of an extensive plasma viral panel performed using PCR were negative, as was the result of the QuantiFERON-TB test.

Electroneuromyography revealed results within the normal range. A comprehensive IgM and IgG antiganglioside panel performed in blood plasma revealed a weakly positive result for IgM antiganglioside GD3.

A four-drug ARV regimen (darunavir/cobicistat, emtricitabine, tenofovir alafenamide and dolutegravir) was initiated to resuppress HIV while the patient was in hospital.

All findings suggested acute inflammatory demyelinating polyneuropathy (AIDP), a subtype of Guillain–Barré Syndrome (GBS). Therefore, treatment was started with intravenous immunoglobulin (IVIG) and a significant improvement was observed after the second cycle.

A follow-up evaluation after 4 months showed complete remission of the neurological symptoms. The CD4+ T cell count and HIV viral load were 794 cells/mm³ (31%) and undetectable, respectively.

We report a case of AIDP-type GBS in a patient with chronic HIV infection who interrupted ART. GBS in HIV-infected individuals is uncommon.¹ It is usually associated with acute HIV infection or preceded by recent viral/bacterial infection in chronically infected individuals.^2,3 In this case, GBS occurred during the chronic phase of HIV infection and was related to interruption of ART that resulted in an increased viral antigen load and a reduction in the CD4 T cell count. This presentation is very unusual, with only two similar cases reported in the literature.^4,5 Both cases occurred during the chronic phase of HIV infection and in one the patient presented with a CD4 T cell count of <200 cells/mm³. Neither had received ART for at least 3 months before onset of GBS.

Other neurological manifestations described after interruption of ART include acute encephalitis and aseptic meningoencephalitis associated with rebound of plasma viral load, regardless of the patient’s immune status.^6,7

The pathogenesis of HIV-related GBS is incompletely understood. Potential mechanisms include direct HIV-induced neurotoxicity or autoimmunity against peripheral myelin glycolipids, which are a secondary cause of demyelination. It was recently suggested that antiganglioside antibodies may play a pathogenic role in the underlying immune mechanism of GBS.^8,9 The presence of antiganglioside antibodies in patients with a low CD4 T cell count may suggest abnormal immunoregulation that leads to a paradoxical increase in autoantibodies, resulting in GBS.¹⁰

Identification of antiganglioside antibodies in GBS can prove useful. Approximately 60% of patients with GBS have antiganglioside antibodies in plasma during the acute clinical phase of the disease, although in AIDP these are rarely present in affected patients and no specific antibody for this variant has yet been found.¹¹ In the case we report, only IgM antiganglioside GD3 yielded a weak-positive result. In 2005, Kaida et al.¹¹ reported the presence of antiganglioside antibodies against GM3, GD3 and GT3 in two patients that appear to be rare cases of chronic IDP and AIDP.

There is insufficient evidence on long-term outcomes of GBS in HIV-infected patients. It has been suggested that GBS may be related to more frequent recurrent episodes in HIV-related GBS than in HIV-negative individuals.

In conclusion, HIV rebound after a short or intermittent interruption of ART can lead to serious neurological complications, such as GBS. GBS must be ruled out in HIV-infected patients with neurological symptoms following discontinuation of ART and plasma viral load rebound.

Funding

This report was carried out as part of our routine work.

Transparency declarations

J.T. has received financial compensation for lectures, consultancies, and educational activities, as well as research funding from Gilead Sciences, Janssen-Cilag, Merck Sharp & Dohme, and ViiV Healthcare. D.M. and M.S. have none to declare. D.P. has received research grants and/or honoraria for advisories and/or conferences from Gilead Sciences, Janssen-Cilag, Merck Sharp & Dohme, and ViiV Healthcare.

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