Effects of patient tracing on estimates of lost to follow-up,
mortality and retention in antiretroviral therapy programs in
low-middle income countries: a systematic review
Effects of patient tracing on estimates of lost to follow-up,
mortality and retention in antiretroviral therapy programs in
low-middle income countries: a systematic reviewJames H.
McMahon1,2, Julian H. Elliott1,3,4, Steven Y. Hong2, Michael R.
Jordan21Infectious Diseases Unit, Alfred Hospital, Melbourne,
Australia; 2Department of Public Health and Community Medicine,
Tufts University School of Medicine, Boston, Massachusetts, USA;
3Department of Medicine, Monash University, and 4Burnet Institute,
Melbourne, Australia
1
BackgroundFrequently reported outcomes for populations receiving
ART include the number of patients: Alive and on
ARTDiedTransferring care from one facility to another (transfer
out)Stopping ART (physician directed or patient initiated) but
remaining in careLost to follow-up (LTFU)2Background -
DefinitionsLTFU - generic term for patients initiating ART with
unknown treatment outcomesUnreported deathsUnknown transfer of care
without documentationDisengagement from care
Retention on ART: patients alive and receiving ART 1Retained on
ART = 1 LTFU - died - stopped ART
Retention at the original site: individuals retained on ART and
excludes transfers out 1Retained at the original site = 1 LTFU died
stopped ART transfer out
31 Fox TMIH 2010, Rosen PLoS Med 2007BackgroundPatient Tracing -
Potential benefits:Improved classification of unknown
outcomesLinking patients disengaged from care back into the health
system
Methods of tracing:Telephone tracingPhysical tracing
Prior reviews1 provide summary estimates of LTFU, mortality and
retention but have not incorporated the potential for patient
tracing to affect these outcomesOr combination of both1 Fox TMIH
2010, Rosen PLoS Med 2007, Gupta PLoS One 2011, Lawn AIDS
200844ObjectiveCompare summary estimates of LTFU, mortality and
retention in low- and middle-income countries (LMICs) 12 months
after ART initiation in cohorts of patients with and without
physical tracing5MethodsSystematic review for studies in LMIC
programmatic settings MEDLINE (2003-2011) HIV conferences (CROI and
IAS 2009-2011)
MeSH and search terms for LTFU and retention
Included studies: reported proportion LTFU 12-months after ART
initiation
Excluded studies: majority children, patients received mono- or
dual-therapy, not performed in LMICs, clinical trials
(non-programmatic setting)6MethodsTracing activities determined
from studies or contacting study authorsClassified as tracing study
if physical tracing available for majority of patients
Summary estimates Medians (IQR) if estimates non-normally
distributed or;Weighted means ( SD) if normally
distributedWeighting of proportions was by the inverse of its
variance [1/(p x [1-p]/n); where p is proportion and n is sample
size]Compared by Students t-test if normally distributed, or
Wilcoxon rank sum test if non-normal
77Identified studies 261 papersIdentified studies 616 conference
abstractsExcluded after reviewing titles and abstracts 149
papersExcluded after reviewing titles 334 conference abstractsFull
text review 112 papersIncluded in the review 32 papersFull text
review 282 conference abstractsIncluded in the review 7 conference
abstracts32 papers and 7 conference abstracts included in the
reviewSearch strategy and study selection8Excluded after reviewing
full text 80 papersExcluded after reviewing full text 275
conference abstractsComparison of summary estimates with and
without physical tracingOutcome ofinterestWith tracingWithout
tracingP value#Cohorts (n)Starting ART (n)Range of estimates
(%)Summary estimate* (%)Cohorts (n)Starting ART (n)Range of
estimates (%)Summary estimate* (%)LTFU25627910.3 - 15.07.6
1.1291248750.8 - 34.815.1 1.7< 0.001Mortality25627914.2 29.710.5
(7.0 12.7)251136931.1 - 15.36.6 (4.3 9.6)0.006Stopped ART13439750.5
5.82.8 0.27108410.8 8.53.2 0.80.5Transfer out569451.0 14.02.7
1.9761951.2 14.53.9 1.30.6Retention on ART256279158.4 88.580.0
(76.5 84.5) 2511369358.5 91.075.8 (70.0 81.2)0.04Retention at
original site256279147.5 88.580.0 (76.0 84.0)2511369358.5 90.672.9
(68.5 79.8)0.02* Values represent median (Q1Q3), or weighted mean
SE (estimates weighted by the inverse of their variance)# Comparing
summary estimates for the 2 groups of studies (tracing and
non-tracing) by Wilcoxon rank-sum test for medians or students t
test for weighted means Notes: LTFU, lost to follow up; ART,
antiretroviral therapy99Discussion LTFU and mortality with physical
tracingUncertain by how much the LTFU was a result of re-engagement
into care versus re-classification of unknown outcomes However, in
addition to LTFU and mortality, we report in retention at the
original siteSuggests tracing may re-engagement in careRetention at
the original site definition accounts for re-classification of lost
patients as died or transferred out10Discussion re-engagement would
lead to beneficial effects of ART 1survival, fewer opportunistic
infections, limiting treatment interruptions (minimizing emergence
of HIV drug resistance), in community HIV viral load
Cost-effectiveness (CE) of tracing not knownPrior CE analyses on
reducing LTFU have not considered tracing 2111 Pallella NEJM 1998,
Parienti CID 2004, Oyugi AIDS 2007, Das PLoS One 2010, Montaner
JAIDS 2010, Andrews JID 2012. 2 Losina PLoS Med
2009DiscussionDifference in summary estimates emphasizes the
importance of knowing whether physical tracing occurs within an ART
program or clinic when interpreting LTFU, mortality or retention
data 1121 2006 WHO IMAI guidelines, 2010 WHO HIVDR Early Warning
Indicators, 2009 UNGASS indicators, 2009 PEPFAR
indicatorsLimitationsART clinics with physical tracing may have
resources resulting in improved outcomesReview of randomized
controlled trials (RCTs) with tracing interventions may provide
more accurate assessments of the impact of tracing on LTFU,
mortality and retentionRCTs not found Needed to quantify benefits
and CE
Transfer out data available in a minority of studies Estimates
of retention at the original site could differ if complete transfer
out data availableEmphasises the importance of understanding
transfer out to accurately interpret estimates of
retention1313ConclusionsPhysical tracing leads to: unknown outcomes
Suggests improved re-engagement in care
Critical need for studies to assess tracing interventions
for:Ability to improve re-engagement of patients on ARTOptimal
methods of tracingCost effectiveness
Programs providing ART in LMICs should consider physically
tracing patients who have unknown outcomes as an intervention to
improve individual outcomes and programmatic evaluation of
populations receiving ART
14AcknowledgementsFinancial supportNational Health and Medical
Research CouncilPostgraduate Scholarship - J.H.MNational Institutes
of Health5K23AI074423-04 - M.R.J., 1K23AI097010-01A1 - S.Y.H.
In addition to study authorsTufts Medical Center / Tufts
UniversityChristine WankeAlfred Hospital / Monash UniversitySharon
LewinWorld Health Organization, HIV Department Silvia
Bertagnolio
15