1. Children Living with HIV in Malawi: Results from the Malawi Population-based HIV Impact Assessment (2016)
Jonnalagadda S1, Bello G2, Saito S3, Burnett J1, Radin E3, Brown K1, Ogollah F3, Cuervo-Rojas J3, Kim E1, Payne D1, Patel H1, Sleeman K1, Hrapcak S1, Voetsch A1 for the MPHIA Study Team
1 U. S. Centers for Disease Control and Prevention
2 Ministry of Health, Government of Malawi
3 ICAP at Columbia University
Good afternoon. I will discuss findings from the pediatric sample of the Malawi Population-based HIV Impact Assessment.
25 July 2017
9th IAS Conference on HIV Science
Center for Global Health
Division of Global HIV & TB

2. Pediatric HIV burden in Malawi
Number of children, 0-14 years, living with HIV (CLHIV) in Malawi: 84,000 (2015 Spectrum estimate)
Derived indirectly from mathematical models
Accurate pediatric HIV burden estimates essential for program planning
Need for pediatric formulations
Testing and treatment coverage in children
Viral suppression in children
Prevention needs in children
Assess PMTCT
Population-based HIV Impact Assessments (PHIAs) directly measure pediatric HIV prevalence (0-14 years) at national level
Based on the 2015 Spectrum model, there were an estimated 84,000 children living with HIV in Malawi.
These estimates are derived indirectly by taking into account a varied set of data inputs and the estimation process is continually improved as new data sources become available and our understanding of the pediatric epidemic grows.
Accurate estimation of the number of children living with HIV is essential not only for forecasting the need for pediatric formulation but also to understand program performance in children such as testing coverage, use of effective treatment and viral suppression. It is also used to plan for prevention needs in children as well as assess performance of PMTCT programs.
These important data needs are being addressed through the population-based HIV impact assessments which are household surveys which are powered to directly measure pediatric HIV prevalence at the national level in 12 countries in sub-Saharan Africa.

3. Malawi Population-based HIV Impact Assessment (MPHIA), 2016
Estimate pediatric HIV prevalence at national level, in children 0-14 years of age
Survey conducted from November 2015 to August 2016
Two-stage cluster design
Stage 1: 500 enumeration areas across 7 zones
Stage 2: 14,268 households; half were sampled for procedures in children
North
North
Central-East
Central-East
Lilongwe city
Lilongwe city
Here we are presenting select results from the survey conducted in Malawi, the Malawi Population-based HIV Impact assessment or MPHIA. As mentioned earlier, measuring national pediatric HIV prevalence was one of the objectives for the survey.
The survey was conducted from October 2015 to August 2016.
MPHIA was a household survey, with a two-stage cluster design. First stage involved selecting 500 enumeration areas sampled from 7 zones; enumeration areas are shown as black dots on the map;
second stage involved sampling 14,268 households. Only half of these household were needed to be sampled for procedures in children to meet the sample size required to estimate national pediatric HIV prevalence.
South-East
Central-West
South-East
Central-West
South-
West
South-West
Blantyre city
Blantyre city

4. Objectives for current analysis using MPHIA 2016 data
Estimate national pediatric prevalence of HIV in Malawi
Estimate the number of children living with HIV (CLHIV)
Estimate viral suppression in HIV positive children
The objectives for the current analyses are;
To estimate national pediatric prevalence of HIV in Malawi
To estimate the number of children living with HIV in Malawi
Viral suppression in all HIV positive children;

5. Sample testing and return of results – MPHIA 2016
Age
Field test
Satellite and Central laboratory
0-17 months
Determine™ (screening RT)*
DNA PCR for confirmation of infection (Early Infant Diagnosis (EID))
Viral load if EID positive
18 months – 14 years
Determine™ (screening RT) and UniGold™ (confirmatory RT)
Geenius™ HIV 1/2 Confirmatory Assay (Bio-Rad)
Viral load if Geenius positive
Next I will talk about sample testing and return of results for children who participated in MPHIA –
Children 0-17 months old, were screened for HIV using a rapid test, at the household and confirmed through DNA PCR testing, also referred to as Early Infant Diagnosis (EID).
A viral load measurement was obtained if child was EID positive.
Children 18 months to 14 years of age were tested for HIV at the household using the national algorithm. Those who tested positive on both the rapid tests underwent further HIV confirmation using a Geenius assay.
All children with confirmed HIV positive status underwent viral load measurement.

6. Sample testing and return of results – MPHIA 2016
Age
Field test
Satellite and Central laboratory
0-17 months
Determine™ (screening RT)*
DNA PCR for confirmation of infection (Early Infant Diagnosis (EID))
Viral load if EID positive
Results returned to clinic ~ 10 weeks
EID positive results returned to household
18 months – 14 years
Determine™ (screening RT) and UniGold™ (confirmatory RT)
Result returned to guardian at household
Geenius™ HIV 1/2 Confirmatory Assay (Bio-Rad)
Viral load if Geenius positive
Result returned to clinic ~ 10 weeks
Results which were returned to the participants are shown on this slide in yellow.
HIV test results in the 18m to 14 yr olds were returned immediately at the household to a guardian.
Viral load and EID results were returned to a clinic identified by the participants. Further, positive EID results were delivered to the household. This is an important service delivery component that was built into this survey and other PHIAs, since these are not stand alone surveys.

7. Analysis of pediatric data – MPHIA 2016
HIV prevalence: EID or Geenius-confirmed HIV positive status
Number of CLHIV was estimated using Malawi National Statistics Office population projection for 2016*
Viral suppression: HIV RNA <1,000 copies/mL
Survey data weighted for design, non-response and non-coverage
For the current analysis, we used confirmed HIV status to estimate HIV prevalence; by confirmed, we mean either EID positive or Geenius confirmed positive.
Children living with HIV was estimated by using the projected population of 0-14 y olds in Malawi.
Viral suppression was defined as HIV RNA level less than 1000 copies/mL
Survey data that was weighted for design and non-response were used in this analysis.
Jackknife replication method was used to estimate variance.
*Census 2008

8. Results

9. Pediatric response rate to blood draw and HIV testing – MPHIA 2016
Sampled: 10,711
Ineligible: 718 (7%)
Eligible: 9,993 (93%)
Blood draw and HIV testing: 6,166 (59%*)
From half of the sampled households that were sub-selected for child procedures, we had a sample of 10,711 children of whom 9,993 or 93% met our eligibility criteria and 6,166 of those eligible, participated in blood collection and HIV testing, giving us a weighted response rate of 59%. The weighted response rate to blood draw and HIV testing is also presented in 5-year age groups below, and the count of children who tested HIV positive in each age-group is shown in the last row of boxes.
Extra notes:
Criteria for inclusion of children (0-14 years)
Resides in selected household, and
Parent reports age of child as between ages 0-14 years, and
Parent is able and willing to provide written, informed consent
Able and willing to provide written assent for those age years
0-4 y: 1,868 (54%*)
5-9 y: 2,201 (60%*)
10-14 y: 2,097 (62%*)
HIV positive: 20
HIV positive: 37
HIV positive: 42
*Weighted response rate to blood draw and HIV testing, among those who are eligible

10. Pediatric HIV burden and viral suppression – MPHIA 2016
National pediatric HIV prevalence: 1.5% (1.1% – 1.9%)
Children living with HIV: 119,500 (89,028 – 149,974)
Viral suppression among HIV positive children: 41.4 % (28.9% – 54.0%)
These are the key results –
The Malawi national HIV prevalence in children was 1.5%.
This translates to a total of 120,000 children living with HIV in Malawi.
Among all HIV positive children, 41% were virally suppressed.

11. Pediatric HIV prevalence, by age – MPHIA 2016
HIV prevalence varied by age group. 2.1% prevalence in the year olds and 1.1% in children 4 and under.
This difference in prevalence across birth cohorts might closely track the evolution of the PMTCT program in Malawi.

12. Pediatric HIV prevalence and PMTCT program in Malawi
MPHIA field work
(2015 – 16)
To examine this, instead of age on the x-axis, we have shown the year of birth of MPHIA participants – for e.g. the10-14 years olds in MPHIA were born between 2002 to 2006 and the 0-4 years in MPHIA were born between 2012 to 2016.
We conducted MPHIA in

13. Pediatric HIV prevalence and PMTCT program in Malawi
AZT for mother from 28 weeks and single dose NVP for mother and child at birth
MPHIA field work
(2015 – 16)
Back in 2002, when the 14 years olds in our survey were born, the PMTCT program involved AZT and NVP.

14. Pediatric HIV prevalence and PMTCT program in Malawi
AZT for mother from 28 weeks and single dose NVP for mother and child at birth
Malawi introduces Option B+, lifelong ART to HIV positive pregnant women
MPHIA field work
(2015 – 16)
In 2011, Malawi introduced option B+ which achieved high national coverage by The youngest children in our survey, 0-4 year olds, were born during the era of option B+.
Couple of things to note – firstly, this prevalence, particularly in the older children is likely an underestimate due to mortality in children living with HIV. And secondly, we note that while the point estimates differ from older to younger birth cohort, the difference is not significant.

15. Geographic variation in pediatric HIV prevalence – MPHIA 2016
North (1.0%)
Lilongwe city (1.4%)
Central-East (0.8%)
Central-West (0.5%)
South-East (2.9%)
This map of Malawi shows the geographic distribution of HIV prevalence in children, which ranges from 0.5% in Central-West to ~3% in South-East. And this map mirrors the MPHIA HIV prevalence map in adults.
South-West (2.2%)
Blantyre city (2.5%)

16. CLHIV burden in the southern zone – MPHIA 2016
70% of 120,000 CLHIV live in the southern zone (~84,000)
North (1.0%)
Lilongwe city (1.4%)
Central-East (0.8%)
Central-West (0.5%)
South-East (2.9%)
Using zonal prevalence estimates and the 2016 population projection, we see that nearly 70% of children living with HIV are in the southern zone of Malawi.
South-West (2.2%)
Blantyre city (2.5%)

17. Viral suppression among CLHIV, by age – MPHIA 2016
Viral suppression was estimated among all HIV positive children as 41% and it was 19% in the youngest children aged 4 and under. And although viral suppression was relatively higher in the older age groups, it is still sub-optimal and quite low compared to what we saw in the adults. This is relevant in the context that some of these adolescents are sexually active and may contribute to transmission.

18. CLHIV, treatment coverage and viral suppression
Spectrum 2015 estimate of CLHIV: 84,000
Treatment coverage among CLHIV: 61%
Spectrum 2016 estimate of CLHIV: 110,000
MPHIA 2016 pediatric prevalence data input into Spectrum
Several other methodologic changes made to pediatric estimation process
With revised larger denominator of CLHIV, treatment coverage may be smaller
MPHIA 2016 viral suppression in CLHIV was 41%
Let’s discuss these last two slides showing number of CLHIV and viral suppression –
Based on the 2015 Spectrum estimate of CLHIV of 84,000, treatment coverage in children was reported at 61%.
The recently released 2016 Spectrum estimate of CLHIV in Malawi, is 110,000. Note that this estimates takes MPHIA pediatric HIV prevalence data into account, methodologic changes.
Now with a revised estimate of 110,000, treatment coverage may be smaller than previously thought.
Viral suppression in children is not an output from Spectrum. MPHIA was the first attempt at measuring community-level viral suppression, i.e. among all children living with HIV and we estimated that to be at 41%.
(Additional information)
Malawi Q4 data - ART coverage was 66% (53,336 / 81,000) for children
LIMS - Viral suppression rates among children (0-14 years) and adults (15+ years) were 62% and 90%, respectively

19. Next steps: Pediatric 90-90-90 cascade
First 90 - Aware
HIV testing history reported by guardian
Second 90 – On ART
Treatment data on children
Third 90 – Virally suppressed
Are children on treatment able to suppress the virus?
In order to understand these results better, our next step is to attempt to build the cascade in children. Additional data on children who participated in MPHIA will soon be ready which will help us understand –
The first 90: did the parent/guardian report a child’s HIV positive status? If this indicator is low, it points towards a need for strengthening case finding in children.
The second 90: we will have biomarker testing data to detect the presence of ARVs in blood.
The third 90: We have viral suppression data but along with the awareness and treatment data, we might be able to better explain the low viral suppression being seen at the community level. Is the gap at the level of not identifying, testing, and treating children or is it adherence or other treatment related issues?
If numbers allow, we could build this cascade by age-group.
Limitation –
Challenge is limited sample size…
Good news – few pediatric cases
Bad news – small sample

20. Acknowledgement MPHIA study participants MPHIA field teams
Malawi Ministry of Health
CDC Atlanta and CDC Malawi
ICAP at Columbia University, NY and ICAP Malawi
Centre for Social Research (CSR)
National Statistical Office (NSO)
Johns Hopkins Project – College of Medicine
WESTAT
This project is supported by the U.S. President’s Emergency Plan for AIDS Relief (PEPFAR) through CDC under the terms of cooperative agreement #U2GGH The contents of this document do not necessarily reflect the views of the United States Government.
With that, I would like to acknowledge the following, extend my thanks for the opportunity to share these results here and invite questions.