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Central nervous system disorders after starting antiretroviral therapy in South Africa

Asselman, Valeriea; Thienemann, Friedrichb,c; Pepper, Dominique Jd,e; Boulle, Andrewf; Wilkinson, Robert Ja,b,d,g,h; Meintjes, Graemea,b,d,g; Marais, Suzaana,b,d

doi: 10.1097/QAD.0b013e328340fe76
Epidemiology and Social: Concise Communications

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 6 months was recorded.

Results: Seventy-five patients were enrolled. The median nadir CD4+ cell counts was 64 cells/μl. Fifty-nine percent of the patients were receiving antituberculosis treatment. The incidence of referral for CNS deterioration in the first year of ART was 23.3 cases [95% confidence interval (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 five. At 6 months, 23% of the 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.

aDepartment of Medicine, GF Jooste Hospital, South Africa

bDepartment of Medicine, University of Cape Town, Cape Town, South Africa

cDepartment of Gastroenterology, Infectious Diseases and Rheumatology, Charité, Campus Benjamin Franklin, Berlin, Germany

dClinical Infectious Diseases Research Initiative, Institute of Infectious Diseases and Molecular Medicine, University of Cape Town, Cape Town, South Africa

eDepartment of Internal Medicine, University of Mississippi Medical Center, Jackson, Mississippi, USA

fSchool of Public Health and Family Medicine, Faculty of Health Sciences, University of Cape Town, Cape Town, South Africa

gDepartment of Medicine, Imperial College London, United Kingdom

hMRC National Institute for Medical Research, London, United Kingdom.

Received 15 July, 2010

Revised 15 September, 2010

Accepted 22 September, 2010

Correspondence to Dr Suzaan Marais, MBChB, Department of Medicine, GF Jooste Hospital, Manenberg, 7764 Cape Town, South Africa. Tel: +27 79 501 3242; fax: +27 21 692 0289; e-mail:

© 2010 Lippincott Williams & Wilkins, Inc.