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

Infectious Diseases Institute, Kampala, Uganda.
Clinical Infectious Diseases (Impact Factor: 8.89). 09/2009; 49(6):965-72. DOI: 10.1086/605500
Source: PubMed


Although many studies have reported high early mortality among patients enrolled in antiretroviral therapy (ART) programs in sub-Saharan Africa-particularly among those individuals with advanced immunodeficiency-few studies have reported the most common causes of these early deaths.
We determined cause-specific mortality and the contribution of immune reconstitution inflammatory 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 limited.
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.

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    • "We included in the multivariate models all variables associated with attrition from the univariate analysis (at p<0.20 level). Age was grouped as 18–30, 31–40, 41–50 and 51–60+ years; baseline CD4 cell count was dichotomized using the standard clinical cut-off of 100 cells per mm3 for HIV to AIDS progression [14], [15], [18], [20], [25]. Both the Akaike and Bayesian Information Criteria (AIC/BIC) were used to assess model parsimony. "
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    ABSTRACT: Background The outcomes from an antiretroviral treatment (ART) program within the public sector in Myanmar have not been reported. This study documents retention and the risk factors for attrition in a large ART public health program in Myanmar. Methods A retrospective analysis of a cohort of adult patients enrolled in the Integrated HIV Care (IHC) Program between June 2005 and October 2011 and followed up until April 2012 is presented. The primary outcome was attrition (death or loss-follow up); a total of 10,223 patients were included in the 5-year cumulative survival analysis. Overall 5,718 patients were analyzed for the risk factors for attrition using both logistic regression and flexible parametric survival models. Result The mean age was 36 years, 61% of patients were male, and the median follow up was 13.7 months. Overall 8,564 (84%) patients were retained in ART program: 750 (7%) were lost to follow-up and 909 (9%) died. During the 3 years follow-up, 1,542 attritions occurred over 17,524 person years at risk, giving an incidence density of 8.8% per year. The retention rates of participants at 12, 24, 36, 48 and 60 months were 86, 82, 80, 77 and 74% respectively. In multivariate analysis, being male, having high WHO staging, a low CD4 count, being anaemic or having low BMI at baseline were independent risk factors for attrition; tuberculosis (TB) treatment at ART initiation, a prior ART course before program enrollment and literacy were predictors for retention in the program. Conclusion High retention rate of IHC program was documented within the public sector in Myanmar. Early diagnosis of HIV, nutritional support, proper investigation and treatment for patients with low CD4 counts and for those presenting with anaemia are crucial issues towards improvement of HIV program outcomes in resource-limited settings.
    PLoS ONE 09/2014; 9(9):e108615. DOI:10.1371/journal.pone.0108615 · 3.23 Impact Factor
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    • "Nevertheless, early initiation of HAART during TB treatment is strongly associated with the occurrence of IRIS [8,9]. Although deaths resulting directly from TB IRIS appear to be limited, the development of IRIS usually results in higher hospitalization rate, interruption of TB treatment and longer time to resolution [10,11]. "
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    ABSTRACT: Background Optimal timing for initiating highly active antiretroviral therapy (HAART) in HIV-TB coinfected patients is challenging for clinicians. We aim to evaluate the impact of different timing of HAART initiation on TB outcome of HIV-infected adults in Taiwan. Methods A population-based retrospective cohort study was conducted through linking the HIV and TB registries of Taiwan Centers for Disease Control (CDC) during 1997 to 2006. Clinical data of HIV-TB co-infected patients, including the presence of immune reconstitution inflammatory syndrome (IRIS), was collected through medical records review. The outcome of interest was all-cause mortality within 1 year following TB diagnosis. The Cox proportional hazard model was used to explore the probability of death and IRIS after TB diagnosis by adjusting for confounding factors and factors of interest. The probability of survival and TB IRIS were calculated by the Kaplan-Meier method and compared between different HAART initiation timing groups by the log-rank test. Results There were 229 HIV-TB co-infected patients included for analysis and 60 cases (26.2%) died within one year. Besides decreasing age and increasing CD4 lymphocyte count, having started HAART during TB treatment was significantly associated with better survival (adjusted Hazard Ratio was 0.11, 95% CI 0.06–0.21). As to the timing of HAART initiation, there was only non-significant benefit on survival among cases initiating HAART within 15 days, at 16–30 days and at 31–60 days of TB treatment than initiating after 60 days. Cases with HAART initiated after 30 days had lower risk in developing IRIS than cases with HAART initiated earlier. Cases with IRIS had significantly higher rate of re-hospitalization (49% vs. 4%, p < 0.001) and prolonged hospitalization (28 days vs. 18.5 days, p < 0.01). Conclusion The present study found that starting HAART during TB treatment is associated with better one-year survival, although earlier initiation within 60 days of TB treatment did not show statistical differences in survival than later initiation. Initiation of HAART within 30 days appeared to increase the risk of IRIS. Deferring HAART to 31–60 days of TB treatment might be optimal after considering the risks and benefits.
    BMC Infectious Diseases 06/2014; 14(1):304. DOI:10.1186/1471-2334-14-304 · 2.61 Impact Factor
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    • "Self reported adherence is measured at each of the study visits. Details of the Research Cohort procedures have been published previously [14], [15]. "
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    ABSTRACT: In sub-Saharan Africa, a large proportion of HIV positive patients on antiretroviral therapy (ART) are lost to follow-up, some of whom are dead. The objective of this study was to validate methods used to correct mortality estimates for loss-to-follow-up using a cohort with complete death ascertainment. Routinely collected data from HIV patients initiating first line antiretroviral therapy (ART) at the Infectious Diseases Institute (IDI) (Routine Cohort) was used. Three methods to estimate mortality after initiation were: 1) standard Kaplan-Meier estimation (uncorrected method) that uses passively observed data; 2) double-sampling methods by Frangakis and Rubin (F&R) where deaths obtained from patient tracing studies are given a higher weight than those passively ascertained; 3) Nomogram proposed by Egger et al. Corrected mortality estimates in the Routine Cohort, were compared with the estimates from the IDI research observational cohort (Research Cohort), which was used as the "gold-standard". We included 5,633 patients from the Routine Cohort and 559 from the Research Cohort. Uncorrected mortality estimates (95% confidence interval [1]) in the Routine Cohort at 1, 2 and 3 years were 5.5% (4.9%-6.3%), 6.6% (5.9%-7.5%) and 7.4% (6.5%-8.5%), respectively. The F&R corrected estimates at 1, 2 and 3 years were 11.2% (5.8%-21.2%), 15.8% (9.9%-24.8%) and 18.5% (12.3% -27.2%) respectively. The estimates obtained from the Research Cohort were 15.6% (12.8%-18.9%), 17.5% (14.6%-21.0%) and 19.0% (15.3%-21.9%) at 1, 2 and 3 years respectively. Using the nomogram method in the Routine Cohort, the corrected programme-level mortality estimate in year 1 was 11.9% (8.0%-15.7%). Mortality adjustments provided by the F&R and nomogram methods are adequate and should be employed to correct mortality for loss-to-follow-up in large HIV care centres in Sub-Saharan Africa.
    PLoS ONE 12/2013; 8(12):e83524. DOI:10.1371/journal.pone.0083524 · 3.23 Impact Factor
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