1. Earlier treatment and lower mortality in infants Initiating ART at <12 weeks of age in South Africa, Victoria Iyun, Karl Technau, Brian Eley, Helena Rabie, Andrew Boulle, Geoff Fatti, Frank Tanser, Robin Wood, Lee Fairlie, Mary-Ann Davies 9th IAS Conference on HIV Science Paris, July
Support for this study was provided by the US National Institute of Allergy and Infectious Diseases (NIAID) and the Eunice Kennedy Shriver National Institute of Child Health and Human Development through the International epidemiologic Databases to Evaluate AIDS, Southern Africa (IeDEA-SA), grant number U01AI069924

2. Conflicts of interest
None to declare.

3. Background
Expansion of universal ART for HIV-infected infants under 5 years - WHO recommendations in 2008 (<1 year), 2010 (<2 years) and 2013 (< 5 years)
Shift towards early infant diagnosis (EID) & early infant antiretroviral therapy (EIART)
more recent (2015) shift towards birth early infant diagnosis (EID) of HIV in South Africa.
Little is known of the outcomes of EIART cohorts initiating ART
In routine care, resource limited settings - in the era of widespread PMTCT and ART
Objective: Describe temporal trends in characteristics of infants at ART initiation and outcomes by 6 months on ART
Outcomes:
Mortality and loss to follow-up (LTFU) by 6 months on ART
LTFU: No clinic visit between months from ART start – date of LTFU = last visit date plus 3 months.
No follow-up after ART initiation & Loss to follow-up after subsequent visit

4. Methods
Median time from ART initiation to death and LTFU at 6 months after ART initiation was estimated
Kaplan-Meier method.
Associations between characteristics at ART start and mortality was assessed
Cox Proportional Hazards models stratified by site.
Characteristics and outcomes were described using three guideline periods; , and >2013, to capture the context of changing paediatric HIV testing and treatment guidelines in South Africa.

5. Table 1: Population characteristics at ART initiation
(n=411)
(n=470)
≥ 2013
(n=499)
Overall
(N=1380)
Age in days
61 (46-75)
60 (39-76)
34 (1-66)
56 (27-73)
Female
208 (50.6)
289 (61.5)
257 (51.5)
754 (54.6)
Absolute CD4 (cells/µL)
888 ( )
1271 ( )
1526 ( )
1217 ( )
Log viral load (copies/ml)
5.90 ( )
6.0 ( )
5.4 ( )
5.86 ( )
WHO stage 3 or 4
250 (83.6)
153 (53.3)
109 (39.0)
512 (59.2)
WAZ ≤ -2
173 (70.0)
116 (54.5)
79 (40.9)
368 (56.4)
Proportions are shown as n (%). Continuous variables are reported as median (interquartile range).

6. Mortality and LTFU at 6 months on ART
>2013
>2013
Overall
≥ 2013
Log rank test
Mortality
78 (5.7%)
40 (9.7%)
19 (4.0%)
19 (4.8%)
<0.001
Among those LTFU, 72% had no follow up after ART while 28% were LTFU after at least one subsequent visit on ART.
Loss to follow-up
225 (17.6%)
92 (22.4%)
76 (16.2%)
57 (14.4%)
0.004 P=

7. Table 2: Predictors of mortality at 6 months on ART
Characteristics
Univariate
Multivariate HR
95% CI
p-value
AHR
Age (months),<1month
reference
1-2 months
1.45
0.320
0.71
0.561
2-3 months
1.57
0.183
0.65
0.478
WHO stage 1 or 2
Stage 3 or 4
1.99
0.020
0.92
0.839
Absolute CD4
0.99
0.051
0.219
WAZ ≤ -2
> -2
0.39
0.002
0.50
0.072
ART initiation period
0.001
0.62
0.217
>2013
0.46
0.005
0.67
0.422 .

8. Result synthesis and conclusion
Children are starting ART earlier
Less advanced disease
Declines in mortality
after adjustment, time period not associated with mortality
baseline characteristics impacting more than period of initiation
Mortality:
Significant proportion of children still start ART with advanced disease ≃ 40%
Recent mortality estimates unacceptably high  ≃ 5%
Loss to follow-up:
Remains high overall ≃ 14%
`No follow-up on ART was particularly high; group requires further research to improve infant retention
Innovative approaches are required to ensure HIV-infected infants in routine care settings achieve optimal treatment outcomes