Two forms of immunological recovery and immune reconstitution inflammatory syndrome in one patient

Two weeks later, he re-presented with lethargy, cough and night sweats. He reported compliance with both ART and anti-TB therapy. His HIV viral load had dropped to 1460 copies/µL, and his CD4 count had increased to 30/µL. A chest x-ray showed changes indicating a worsening of his condition and suggesting TB immune reconstitution inflammatory syndrome (IRIS). Both anti-TB therapy and ART were continued. Seventeen days after restarting ART, he developed weakness in his left arm and leg. Magnetic resonance imaging (MRI) of the brain showed white matter lesions with oedema in the right frontoparietal region, suggesting possible progressive multifocal leukoencephalopathy (PML) IRIS (Box). JC (John Cunningham) virus was not detected on initial cerebrospinal fluid polymerase chain reaction testing, but the diagnosis of PML was confirmed 3 months later, when the patient presented with a symptom flare and worsening changes apparent on MRI. A brain biopsy showed a perivascular inflammatory infiltrate of lymphocytes, and JC virus was detected in oligodendrocytes by Simian virus 40/BK virus immunostain. Corticosteroids were added, after which his condition slowly improved. He was eventually discharged to supported accommodation.

The beneficial immunological effects of ART result from the restoration of pathogen-specific immune responses.1 However, although recovery of immune function has substantial clinical benefits, it is sometimes accompanied by paradoxical adverse effects, including IRIS.

The timing of initiation of ART in patients co-infected with TB and HIV poses a dilemma. On the one hand, there is an increased risk of IRIS when anti-TB therapy and ART are commenced concurrently.2,3 On the other hand, recent studies have shown that delaying ART leads to higher rates of mortality and morbidity, particularly with CD4 counts of less than 50/µL.1,4 Despite the potential for complications associated with immune restoration, prompt institution of ART was necessary in our patient, given the risks of severe prolonged immunodeficiency. Although ART unmasked PML, it was ultimately crucial in the patient’s survival from this infection.

Magnetic resonance imaging of the brain at hemiparesis onset (A, B and C) and 3 months later (D, E and F)*

* T2 weighted (A and D), fluid attenuated inversion recovery (FLAIR) (B and E) and contrast enhanced T1 (C and F) sequences showing marked progression of findings, with extension of white matter lesions, mass effect with effacement of the sulci and new contrast enhancement — consistent with progressive multifocal leukoencephalopathy immune reconstitution inflammatory syndrome