Mortality in Patients with HIV-1 Infection Starting Antiretroviral Therapy in South Africa, Europe, or North America: A Collaborative Analysis of Prospective Studies

High early mortality in patients with HIV-1 starting antiretroviral therapy (ART) in sub-Saharan Africa, compared to Europe and North America, is well documented. Longer-term comparisons between settings have been limited by poor ascertainment of mortality in high burden African settings. This study...

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Published in:PLoS medicine Vol. 11; no. 9; p. e1001718
Main Authors: Boulle, Andrew, Schomaker, Michael, May, Margaret T., Hogg, Robert S., Shepherd, Bryan E., Monge, Susana, Keiser, Olivia, Lampe, Fiona C., Giddy, Janet, Ndirangu, James, Garone, Daniela, Fox, Matthew, Ingle, Suzanne M., Reiss, Peter, Dabis, Francois, Costagliola, Dominique, Castagna, Antonella, Ehren, Kathrin, Campbell, Colin, Gill, M. John, Saag, Michael, Justice, Amy C., Guest, Jodie, Crane, Heidi M., Egger, Matthias, Sterne, Jonathan A. C.
Format: Journal Article
Language:English
Published: United States Public Library of Science 01.09.2014
Public Library of Science (PLoS)
Subjects:
Acquired immune deficiency syndrome
Adult
AIDS
Analysis
Anti-HIV Agents - therapeutic use
Antiretroviral Therapy, Highly Active - mortality
Antiretroviral Therapy, Highly Active - trends
Antiviral agents
Biology and Life Sciences
Care and treatment
Cohort Studies
Cooperative Behavior
Drug therapy
Europe
Europe - epidemiology
Female
Follow-Up Studies
Health aspects
Highly active antiretroviral therapy
HIV
HIV infection
HIV Infections - drug therapy
HIV Infections - mortality
HIV patients
HIV-1
Human immunodeficiency virus
Human immunodeficiency virus 1
Humans
Male
Medicine and Health Sciences
Middle Aged
Mortality
Mortality - trends
North America
North America - epidemiology
Patient outcomes
Prospective Studies
Risk factors
South Africa
South Africa - epidemiology
Studies
South Africa
North America
Europe
ISSN:1549-1676, 1549-1277, 1549-1676
Online Access:Get full text
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Summary:High early mortality in patients with HIV-1 starting antiretroviral therapy (ART) in sub-Saharan Africa, compared to Europe and North America, is well documented. Longer-term comparisons between settings have been limited by poor ascertainment of mortality in high burden African settings. This study aimed to compare mortality up to four years on ART between South Africa, Europe, and North America. Data from four South African cohorts in which patients lost to follow-up (LTF) could be linked to the national population register to determine vital status were combined with data from Europe and North America. Cumulative mortality, crude and adjusted (for characteristics at ART initiation) mortality rate ratios (relative to South Africa), and predicted mortality rates were described by region at 0-3, 3-6, 6-12, 12-24, and 24-48 months on ART for the period 2001-2010. Of the adults included (30,467 [South Africa], 29,727 [Europe], and 7,160 [North America]), 20,306 (67%), 9,961 (34%), and 824 (12%) were women. Patients began treatment with markedly more advanced disease in South Africa (median CD4 count 102, 213, and 172 cells/µl in South Africa, Europe, and North America, respectively). High early mortality after starting ART in South Africa occurred mainly in patients starting ART with CD4 count <50 cells/µl. Cumulative mortality at 4 years was 16.6%, 4.7%, and 15.3% in South Africa, Europe, and North America, respectively. Mortality was initially much lower in Europe and North America than South Africa, but the differences were reduced or reversed (North America) at longer durations on ART (adjusted rate ratios 0.46, 95% CI 0.37-0.58, and 1.62, 95% CI 1.27-2.05 between 24 and 48 months on ART comparing Europe and North America to South Africa). While bias due to under-ascertainment of mortality was minimised through death registry linkage, residual bias could still be present due to differing approaches to and frequency of linkage. After accounting for under-ascertainment of mortality, with increasing duration on ART, the mortality rate on HIV treatment in South Africa declines to levels comparable to or below those described in participating North American cohorts, while substantially narrowing the differential with the European cohorts. Please see later in the article for the Editors' Summary.
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MSS is the local principal investigator on studies sponsored by Abbvie, Gilead, BMS, Merck, BI, ViiV, and Jannsen, where funding goes directly to the institution but not to MSS. PR, through his institution, has received independent scientific grant support from Gilead Sciences, Janssen Pharmaceutica N.V., Merck&Co, Bristol-Myers Squibb, and ViiV Healthcare, and travel support through his institution from Gilead Sciences and Janssen Pharmaceutica N.V. In addition, PR has served on a scientific advisory board for Gilead Sciences and serves on a data safety monitoring committee for Janssen Pharmaceutica N.V., for which his institution has received remuneration. KE has received honoraria from Abbott for educational lectures. JS has received research grants from the UK Medical Research Council. JS has received payment from Gilead Sciences, Inc for educational presentations.
Conceived and designed the experiments: AB MS MTM RSH BES SM OK FL JG JN DG MF SMI PR FD DC AC KE CC MJG MS ACJ JG HMC ME JACS. Analyzed the data: MS AB MM JACS. Wrote the first draft of the manuscript: AB. Contributed to the writing of the manuscript: MS MTM RSH BES SM OK FL JG JN DG MF SMI PR FD DC AC KE CC MJG MS ACJ JG HMC ME JACS. ICMJE criteria for authorship read and met: AB MS MTM RSH BES SM OK FL JG JN DG MF SMI PR FD DC AC KE CC MJG MS ACJ JG HMC ME JACS. Agree with manuscript results and conclusions: AB MS MTM RSH BES SM OK FL JG JN DG MF SMI PR FD DC AC KE CC MJG MS ACJ JG HMC ME JACS.
ISSN:1549-1676
1549-1277
1549-1676
DOI:10.1371/journal.pmed.1001718