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

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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

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