Mortality of Patients Lost to Follow-Up in Antiretroviral Treatment Programmes in Resource-Limited Settings: Systematic Review and Meta-Analysis

Division of International and Environmental Health, Institute of Social and Preventive Medicine (ISPM), University of Bern, Bern, Switzerland.
PLoS ONE (Impact Factor: 3.23). 06/2009; 4(6):e5790. DOI: 10.1371/journal.pone.0005790
Source: PubMed


The retention of patients in antiretroviral therapy (ART) programmes is an important issue in resource-limited settings. Loss to follow up can be substantial, but it is unclear what the outcomes are in patients who are lost to programmes.
We searched the PubMed, EMBASE, Latin American and Caribbean Health Sciences Literature (LILACS), Indian Medlars Centre (IndMed) and African Index Medicus (AIM) databases and the abstracts of three conferences for studies that traced patients lost to follow up to ascertain their vital status. Main outcomes were the proportion of patients traced, the proportion found to be alive and the proportion that had died. Where available, we also examined the reasons why some patients could not be traced, why patients found to be alive did not return to the clinic, and the causes of death. We combined mortality data from several studies using random-effects meta-analysis. Seventeen studies were eligible. All were from sub-Saharan Africa, except one study from India, and none were conducted in children. A total of 6420 patients (range 44 to 1343 patients) were included. Patients were traced using telephone calls, home visits and through social networks. Overall the vital status of 4021 patients could be ascertained (63%, range across studies: 45% to 86%); 1602 patients had died. The combined mortality was 40% (95% confidence interval 33%-48%), with substantial heterogeneity between studies (P<0.0001). Mortality in African programmes ranged from 12% to 87% of patients lost to follow-up. Mortality was inversely associated with the rate of loss to follow up in the programme: it declined from around 60% to 20% as the percentage of patients lost to the programme increased from 5% to 50%. Among patients not found, telephone numbers and addresses were frequently incorrect or missing. Common reasons for not returning to the clinic were transfer to another programme, financial problems and improving or deteriorating health. Causes of death were available for 47 deaths: 29 (62%) died of an AIDS defining illness.
In ART programmes in resource-limited settings a substantial minority of adults lost to follow up cannot be traced, and among those traced 20% to 60% had died. Our findings have implications both for patient care and the monitoring and evaluation of programmes.

Download full-text


Available from: Mar Pujades-Rodríguez,
  • Source
    • "Two previous reviews have highlighted the substantial numbers of self-transfers amongst LTFU patients. The first, a systematic review, reported self-transfer rates of 12–54% amongst patients found alive (Brinkhof et al. 2009). The second, a narrative review, estimated a crude unweighted median self-transfer rate of 48.5% amongst those reported in 14 cited studies as LTFU (Geng et al. 2010b). "
    [Show abstract] [Hide abstract]
    ABSTRACT: Objective To ascertain estimates of adult patients, recorded as lost to follow-up (LTFU) within antiretroviral treatment (ART) programmes, who have self-transferred care, died or truly stopped ART in low- and middle-income countries.Methods PubMed, EMBASE, Web of Science, Science Direct, LILACS, IndMed and AIM databases (2003-2013) and IAS/AIDS conference abstracts (2011-2013) were searched for tracing studies reporting the proportion of traced patients found to have self-transferred, died or stopped ART. These estimates were then combined using random-effects meta-analysis. Risk of bias was assessed through subgroup and sensitivity analyses.Results28 studies were eligible for inclusion, reporting true outcomes for 10,806 traced patients attending approximately 258 ART facilities. None were from outside sub-Saharan Africa. 23 studies reported 4.5-54.4% traced LTFU patients self-transferring care, providing a pooled estimate of 18.6% (95% CI 15.8-22.0%). A significant positive association was found between rates of self-transfer and LTFU in the ART cohort. The pooled estimates for unreported deaths was 38.8% (95% CI 30.8-46.8%; 27 studies), and 28.6% (95% CI 21.9-36.0%; 20 studies) for patients stopping ART. A significant decrease in unreported deaths from 50.0% (95% CI 41.5-58.4%) to 30.0% (95% CI 21.1-38.9%) was found comparing study periods before and after 31/12/2007.Conclusions Substantial unaccounted for transfers and deaths among patients LTFU confirms that retention and mortality is underestimated where the true outcomes of LTFU patients are not ascertained.This article is protected by copyright. All rights reserved.
    Tropical Medicine & International Health 11/2014; 20(3). DOI:10.1111/tmi.12434 · 2.33 Impact Factor
  • Source
    • "Children who lived near a town might have been more likely to attend other ART centres near their homes after their caregivers knew they needed to start ART. However, studies performed in adults have demonstrated a high mortality in LTFU patients,34 as was observed also in a study on children conducted in Western Kenya.35 "
    [Show abstract] [Hide abstract]
    ABSTRACT: Data on attrition due to mortality or loss to follow-up (LTFU) from antiretroviral therapy (ART) eligibility to ART initiation of HIV-infected children are scarce. The aim of this study is to describe attrition before ART initiation of 247 children who were eligible for ART in a cohort study in India. Multivariable analysis was performed using competing risk regression. The cumulative incidence of attrition was 12.6% (95% confidence interval, 8.7-17.3) after five years of follow-up, and the attrition rate was higher during the first months after ART eligibility. Older children (>9 years) had a lower mortality risk before ART initiation than those aged <2 years. Female children had a lower risk of LTFU before ART initiation than males. Children who belonged to scheduled tribes had a higher risk of delayed ART initiation and LTFU. Orphan children had a higher risk of delayed ART initiation and mortality. Children who were >3 months in care before ART eligibility were less likely to be LTFU. The 12-month risk of AIDS, which was calculated using the absolute CD4 cell count and age, was strongly associated with mortality. A substantial proportion of ART-eligible children died or were LTFU before the initiation of ART. These findings can be used in HIV programmes to design actions aimed at reducing the attrition of ART-eligible children in India.
    Infectious disease reports 05/2014; 6(2):5167. DOI:10.4081/idr.2014.5167
  • Source
    • "Data from South Africa and other countries demonstrate that starting ART earlier (at CD4<350 cells/µL) results in improved treatment outcomes [68]. Similar to other programmes [34], [45], [48], [49], a large proportion of reported mortality in our study population occurred within 6 months of initiating ART. During the period of our study, adults infected with HIV were eligible for ART if they presented with WHO clinical stage IV and/or CD4+ <200 cells/µL. "
    [Show abstract] [Hide abstract]
    ABSTRACT: Since establishment of Zimbabwe's National Antiretroviral Therapy (ART) Programme in 2004, ART provision has expanded from <5,000 to 369,431 adults by 2011. However, patient outcomes are unexplored. To determine improvement in health status, retention and factors associated with attrition among HIV-infected patients on ART. A retrospective review of abstracted patient records of adults ≥15 years who initiated ART from 2007 to 2009 was done. Frequencies and medians were calculated for rates of retention in care and changes in key health status outcomes at 6, 12, 24 and 36 months respectively. Cox proportional hazards models were used to determine factors associated with attrition. Of the 3,919 patients, 64% were female, 86% were either WHO clinical stage III or IV. Rates of patient retention at 6, 12, 24 and 36 months were 90.7%, 78.1%, 68.8% and 64.4%, respectively. After ART initiation, median weight gains at 6, 12, and 24 months were 3, 4.5, and 5.0 kgs whilst median CD4+ cell count gains at 6, 12 and 24 months were 122, 157 and 279 cells/µL respectively. Factors associated with an increased risk of attrition included male gender (AHR 1.2; 95% CI, 1.1-1.4), baseline WHO stage IV (AHR 1.7; 95% CI, 1.1-2.6), lower baseline body weight (AHR 2.0; 95% CI, 1.4-2. 8) and accessing care from higher level healthcare facilities (AHR 3.5; 95% 1.1-11.2). Our findings with regard to retention as well as clinical and immunological improvements following uptake of ART, are similar to what has been found in other settings. Factors influencing attrition also mirror those found in other parts of sub-Saharan Africa. These findings suggest the need to strengthen earlier diagnosis and treatment to further improve treatment outcomes. Whilst decentralisation improves ART coverage it should be coupled with strategies aimed at improving patient retention.
    PLoS ONE 01/2014; 9(1):e86305. DOI:10.1371/journal.pone.0086305 · 3.23 Impact Factor
Show more