Browsing by Subject "Immune Reconstitution Inflammatory Syndrome"

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    Central nervous system disorders afrer starting antiretroviral therapy in South Africa
    (Lippincott, Williams & Wilkins, 2010) Asselman, Valerie; Thienemann, Fredrich; Pepper, Dominique J; Boulle, Andrew; Wilkinson, Robert J; Graeme Meintjes; Marais, Suzaan
    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.
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    Prolonged deferral of antiretroviral therapy in the SAPIT trial: Did we need a clinical trial to tell us that this would increase mortality?
    (2010) Boulle, Andrew; Clayden, Polly; Cohen, Karen; Cohen, Ted; Conradie, Francesca; Dong, Christa; Geffen, Nathan; Grimwood, Ashraf; Hurtado, Rocio; Kenyon, Christopher; Lawn, Stephen; Maartens, Gary; Meintjes, Graeme; Mendelson, Marc; Murray, Megan; Rangaka, Molebogeng; Sanne, Ian; Spencer, David; Taljaard, Jantjie; Variava, Ebrahim; Venter, W D Francois; Wilson, Douglas
    Tuberculosis is the major cause of morbidity and mortality in HIVinfected patients in sub-Saharan Africa. HIV infection is often first diagnosed following a diagnosis of tuberculosis, with many patients needing antiretroviral therapy (ART). Starting ART in HIV-infected patients with tuberculosis (TB) may be associated with complications, including side-effects from co-administration of multiple drugs with many overlapping toxicities, reductions in concentrations of certain antiretroviral drugs following the induction of metabolising enzymes and drug transporters by rifampicin, and paradoxical deterioration due to the immune reconstitution inflammatory syndrome (IRIS). Furthermore, the high pill burden of co-treatment could reduce adherence, resulting in poor treatment outcomes for both diseases. These potential harms must be weighed against the high mortality rates in patients with HIV-associated tuberculosis who do not receive ART, especially those with low CD4 counts. The optimal time to initiate ART in patients with tuberculosis is an important research question, and randomised controlled trials are addressing this issue.