Central nervous system disorders after starting antiretroviral therapy in South Africa

Abstract

Objective To describe the spectrum of central nervous system (CNS) disease during the first year of antiretroviral therapy (ART), and to determine the contribution of neurological immune reconstitution inflammatory syndrome (IRIS). Design A prospective observational cohort study conducted over a 12-month period at a public sector referral hospital in South Africa. Methods HIV seropositive patients who developed new or recurrent neurological or psychiatric symptom(s) or sign(s) within the first year of starting ART were enrolled. We used the number of patients starting ART in the referral area in the preceding year as the denominator to calculate the incidence of referral for neurological deterioration. Patients with delirium and peripheral neuropathy were excluded. Outcome at six months was recorded. Results Seventy-five patients were enrolled. The median nadir CD4+ count was 64 cells/μL. 59% of patients were receiving antituberculosis treatment. The incidence of referral for CNS deterioration in the first year of ART was 23.3 cases (95% CI, 18.3–29.2) per 1000 patient years at risk. CNS tuberculosis (n=27, 36%), cryptococcal meningitis (n=18, 24%), intracerebral space occupying lesions (other than tuberculoma) (n=10, 13%) and psychosis (n=9, 12%) were the most frequent diagnoses. Paradoxical neurological IRIS was diagnosed in 21 patients (28%), related to tuberculosis in 16 and cryptococcosis in 5. At 6 months, 23% of patients had died and 20% were lost to follow-up. Conclusion Opportunistic infections, notably tuberculosis and cryptococcosis, were the most frequent causes for neurological deterioration after starting ART. Neurological IRIS occurred in over a quarter of patients.

Neurologic Complications of HIV-1 Infection and Its Treatment in the Era of Antiretroviral Therapy

“…According to one study, as many as 21% of patients in South Africa have developed Mycobacterium-related CNS-IRIS. 60 Given that one-third of the world's population has been infected with tuberculosis, a greater evidence of mycobacterial CNS-IRIS may emerge as ART increases in availability worldwide. If a patient presents with clinical deterioration and meningeal enhancement on MRI or communicating hydrocephalus in the context of ART initiation with adequate treatment for mycobacteria, IRIS should be strongly considered in the differential diagnosis.…”

“…60 Cryptococcal infections may be associated with 10% to 30% of all CNS-IRIS, 53 most often clinically manifest as aseptic recurrence of prior meningitis and rarely as intracranial cryptococcoma.…”

Neuro-AIDS in the developing world

“…In one study, paradoxical neurologic worsening was observed in 28% of South African patients started on HAART. 4 IRIS has also been described with opportunistic parasitic diseases unique to the developing world, such as schistosomiasis, strongyloidiasis, and leishmaniasis.…”

Brain tuberculosis-associated immune reconstitution inflammatory syndrome in an HIV-positive patient: a biopsy-proven case

“…Of these patients, four had meningitis; five had intracranial space occupying lesions, mainly multiple and with perilesional edema; five had both meningitis and space occupying lesions; one had radiculomyelitis; and one had spondylitis [8]. A recent prospective observational cohort study by Asselman et al [10] in South Africa found CNS tuberculosis in 36% of CNS diseases diagnosed during the first year of HAART; paradoxical neurological IRIS comprised 21% of the diagnoses. In 2012, Guevara-Silva et al reported their experience at a Mexican neurological center, where they found that 9.3% of patients developed cerebral IRIS, two of whom had tuberculosis, and those patients showed a good prognosis [11].…”