Mortality in an ART African Cohort • CID 2009:49 (15 September) • 965
H I V / A I D SM A J O R A R T I C L E
Cause-Specific Mortality and the Contribution
of Immune Reconstitution Inflammatory Syndrome
in the First 3 Years after Antiretroviral Therapy
Initiation in an Urban African Cohort
Barbara Castelnuovo,1Yukari C. Manabe,1,3Agnes Kiragga,1Moses Kamya,2Philippa Easterbrook,4
and Andrew Kambugu1
1Infectious Diseases Institute and
of Infectious Diseases, Johns Hopkins University School of Medicine, Baltimore, Maryland; and
2Department of Medicine, Makerere University, Kampala, Uganda;
3Department of Medicine, Division
4King’s College, London, United Kingdom
(See the editorial commentary by Davies and Meintjes, on pages 973–5.)
Although many studies have reported high early mortality among patients enrolled in antiret-
roviral therapy (ART) programs in sub-Saharan Africa—particularly among those individuals with advanced im-
munodeficiency—few studies have reported the most common causes of these early deaths
We determined cause-specific mortality and thecontributionofimmunereconstitutioninflammatory
syndrome (IRIS) in a well-characterized patient cohort in Kampala, Uganda, over a 36-month period of ART.
In a cohort of patients who initiated antiretroviral therapy in Uganda, we observed a high early
mortality rate among patients with advanced disease. The most common causes of death were tuberculosis and
cryptococcal meningitis. The contribution of immune reconstitution inflammatory syndrome to mortality was
We show a significant early mortality in our ART cohort in resource-limited settings that is
driven by advanced human immunodeficiency virus disease and characterized by low CD4 cell counts. In our
experience, the contribution of IRIS to this observed early mortality is limited.
The dramatic reduction in morbidity and mortality
among human immunodeficiencyvirus(HIV)–infected
individuals who initiated antiretroviral therapy (ART)
in resource-limited settings has mirrored reductions in
morbidity and mortality among such patients in de-
veloped countries [1–4]. However, the considerable
gains that have been made by HIV treatment programs
in resource-limited settings have been tempered by on-
going reports of high early mortality and high rates of
loss to follow up among individuals receiving ART [5–
10]. Investigations involving patients who have been
lost to follow up have revealed that a high proportion
Received 13 January 2009; accepted 5 May 2009; electronically published 12
Reprints or correspondence: Dr. Barbara Castelnuovo, Infectious Diseases
Institute, Mulago Hospital Complex, PO Box 22418 Kampala, Uganda
Clinical Infectious Diseases2009;49:965–72
? 2009 by the Infectious Diseases Society of America. All rights reserved.
of such individuals are lost to follow up as a result of
death [6, 11–13]. Therefore, previous mortality esti-
mates for ART rollout programs in sub-Saharan Africa
are likely to have underestimated true HIV-related and
ART-related mortality [14, 15].
Although many studies have reported high early
mortality among patients enrolled in ART programs in
sub-Saharan Africa—particularly among those individ-
uals with advanced immunodeficiency—few studies
have reported the most common causes of these early
deaths . It has become increasingly recognized that
immune reconstitution can precipitate the unmasking
of subclinical infections [16, 17]. A proportion of pa-
tients with these unmasked cases may develop signs of
immune reconstitution inflammatorysyndrome(IRIS),
an exaggerated inflammatory response that was first
described in patients with treated opportunistic infec-
tions that paradoxically worsened with ART initiation
. Although it was anticipated that IRIS would be a
major problem in ART rollout programs in resource-
limited settings because of low CD4 cell counts at ART
by guest on December 27, 2015
972 • CID 2009:49 (15 September) • Castelnuovo et al
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