Failure to Initiate ART, Loss to Follow-up and Mortality among HIV-infected Patients during the

pre-ART period in Uganda

Elvin H. Geng1, Winnie Muyindike2, David V. Glidden1, Mwebesa B. Bwana2, Constantin T. Yiannoutsos3, Paula Braitstein3, Nicholas Musinguzi2,

David R. Bangsberg4, Jeffrey N. Martin1 University of California San Francisco1; Mbarara University of Science and Technology, Mbarara,

Uganda2; Indiana University3 and Harvard Medical School4 for the East Africa International Epidemiologic Databases to Evaluate AIDS

Engagement in care among ART Eligible Patients• For HIV-infected, ART eligible patients with CD4 counts < 250 cells/mm3, timely initiation is crucial and life saving.

• To date, however, delays or failures in ART initiation are not well understood because loss to follow-up is high

• Losses mean that the experience of ART-eligible patients – including the occurrence of mortality, ART initiation and disengagement from care – are partially observed.

• We used a sampling based approach to assess outcomes in a setting where loss to follow-up is common: finding outcomes in a small but random sample of patients LTFU can “fill in the blanks.”

Objectives

• We applied this sampling based approach at a prototypical scale-up ART clinic in Uganda:– High volume (200 patients/day)– Semi-rural environment– Implementing a simplified and standardized “public

health approach” – CD4 testing is routinely available, viral load is not. – 2-3 counseling sessions and a treatment supporter

are customary requirements for ART initiation.

Methods• Patients

– Adult, enrolled between Oct. 1, 2007 and Jan. 27, 2011 with a CD4-based indication for ART (i.e., CD4 < 250 cells/cc3) at the Immune Suppression Syndrome (ISS) Clinic in Mbarara, Uganda.

– A random sample of patients in the community to ascertain updated vital status, whether they continued to see an HIV provider and whether they started ART at another clinic to better understand true outcomes.

• Measurements– Patient data derived from data collected in the course of routine care

• Analyses– Incidence of loss to follow-up (defined as 60 days late for an appointment)

– Competing risks analysis of ART initiation (at original and other clinic), waiting for ART in care, disengagement from care (defined as 90 days without a visit to any facility) and mortality.

– Sampled outcomes incorporated by a probability weight.

All ART- eligible Patients in Clinic

Patients who Continue in Care

Patients lost to follow-up before ART (B)

Patients sought by tracking (C)

Eligible patients with vital status

ascertained by tracking (D)

Pw = LTFU patients (B)

Patients with ascertained outcomes (D)

0.1

.2.3

.4.5

Pro

port

ion

0 30 60 90 120 150 180 210 240 270 300 330 360

Time since ART eligible

Incidence of Loss to Follow-up before ART Initiation

At 1-year: 21.0% (95% CI: 19.3%-22.6%).

2639 ART-eligible patients between 1-Oct-07 and 27-Jan-11

492 (19%) became lost to follow-up

84 (52%) Alive 50 (31%) Died (18%) Not found

49 (58%) as reported by a proxy (i.e., family member)

35 (42%) as reported by patient him/herself

163 (33%) Tracked

6 (17%) started ART at another clinic

16 (46%) seen a HIV provider at another clinic but not on ART

13 (37%) disengaged from care (i.e., not seen an HIV provider)

2639 ART-eligible patients between 1-Oct-07 and 27-Jan-11

492 (19%) became lost to follow-up

84 (52%) Alive 50 (31%) Died (18%) Not found

49 (58%) as reported by a proxy (i.e., family member)

35 (42%) as reported by patient him/herself

163 (33%) Tracked

6 (17%) started ART at another clinic

16 (46%) seen a HIV provider at another clinic but not on ART

13 (37%) disengaged from care (i.e., not seen an HIV provider)

Patients

All patients,

N=2,639 Lost to follow-

up, N=492 Tracked and

found, N=134

Age, median (IQR) 33 (27-40) 32 (27-39) 33 (27-39)

Male Sex, n (%) 744 (41) 212 (42) 56 (42)

Pre-therapy CD4 value (cells/cc3), median (IQR)

125 (47-204) 124 (46-201) 129 (52-213)

0.0

00.

10

0.2

00.

30

0.4

00.

50

0 60 120 180 240 300 360

Time since last visit (days)

Mortality in Random Sample of Patients Lost to Follow-up, N=134

At 1-year: 30.8% (95% CI: 22.9%-40.6%)

Sampling-based Estimate of Outcomes in all ART Eligible Patients

Days since ART eligibility

Prop

ortio

n

Factors Associated with ART Initiation

Conclusions• Although ART initiation is rapid for a subgroup of “on-track” patients during the first 90 days after eligibility, a substantial fraction of ART eligible patients fail to initiate ART.

•Loss to follow-up while waiting for ART is common at a prototypical ART clinic and mortality is high among those who fail to return to their originating clinic.

•A substantial proportion of patients who fail to start ART continue to visit a clinic.

•Year of ART eligibility, potentially reflecting drug supply, was found to influence ART initiation rates.

Implications•The final step from staging to ART in HIV/AIDS care and treatment programs may be accompanied by significant barriers and obstacles.

•Standard procedures such as counseling requirements and treatment supporters, although widespread, should be evaluated to determine their risks vs. benefits.

•If these observations are true elsewhere, in the roll out of ART to date, potentially over a million ART eligible patients failed to initiate ART in Africa, Asia, else where!

•Strategies to fully engage ART-eligible patients represent a public health priority.

Acknowledgements

• UCSF– Jeffrey N. Martin– Dave Glidden

• NIH– Melanie Bacon– Carolyn Williams– Rosemary McKaig

• Indiana University– Constantin Yiannoutsos– Kara Wools Kaloustian– Paula Braitstein

• Mbarara University– Hassan Baryahikwa– Mwebesa Bwana– Nicholas Musinguzi– Winnie Muyindike

• Harvard University – David R. Bangsberg