A closer look at viral suppression and enhanced adherence counselling in children on ART in Zambia

1. Mwango Albert, MDHIVCLINICAL UPDATE
Children's Enhanced Adherence
Counselling in ZambiaAugust 2020

2. Mwango Albert, MDHIVCLINICAL UPDATE
Disclosures and Disclaimers
• Albert Mwango, BScHB, MBChB, MPH
• I have no conflict of interest or disclosures to declare
• The views, thoughts, and opinions expressed in this presentation
belong solely to me, and do not necessarily reflect the official policy
or position of my current employer –CRS or MOH-Zambia or group
or individual
mwangoaj@gmail.com
2

3. Mwango Albert, MDHIVCLINICAL UPDATE
Outline
• Definitions
• Background
• Review of viral load testing and efficacious regimens in children
• Managing suspected treatment failure
• EAC
• Second line ARVs for children

4. Mwango Albert, MDHIVCLINICAL UPDATE
Definitions
• Viral Suppression: when antiretroviral therapy reduces a
person’s viral load to less than 1000c/mL (partial suppression)
or to an undetectable level (full suppression)
• Treatment failure: when antiretroviral therapy fails to control
HIV infection
4

5. Mwango Albert, MDHIVCLINICAL UPDATE
Background
Viral Suppression
Immune Function Restoration
Clinical Improvement
Halting HIV
transmission
Monitoring viral loads and
managing treatment
failure
Monitoring and preserving
immune capacity
Reduce morbidity,
improve QoL and
minimise adverse effects
Reduce new infections
01
04
03
02
Goals of ART
5
Goals of Antiretroviral Therapy

6. Mwango Albert, MDHIVCLINICAL UPDATE
Sustained Viral Suppression
• One of the key goals of ART is to produce sustainable viral
suppression preferably at undetectable levels
• Some of the challenges faced by clinicians in resource limited
settings in managing ART are:
• Interpreting viral load testing results
• Managing suspected treatment failure
• Choice of regimens when preferred first line ARVs fail

7. Mwango Albert, MDHIVCLINICAL UPDATE
Viral Loads in Children (at Zambia National Level)
7
58%
Viral Suppression in Children
UNAIDS 2020 DATA

8. Mwango Albert, MDHIVCLINICAL UPDATE
Key slides from w.01
8

9. Mwango Albert, MDHIVCLINICAL UPDATE
Take home from previous discussions
• We reviewed:
• How to monitor ART using Viral load testing
• How use Log10 to better describe changes in viral load
• Expected maximal Log10 changes in viral load on various regimens
• Normal routine viral load testing for adults, children and PBFW
9

10. Mwango Albert, MDHIVCLINICAL UPDATE
Reduction in VL on various regimens
10

11. Mwango Albert, MDHIVCLINICAL UPDATE
Viral suppression (<1000c/mL)
• During the first two years following ART
initiation:
• After 2yrs more Children (>13 months of age) than
Infants achieved “partial” suppression (<1000c/ml)
• By 24 months on ART, 93% of children and 81% of
infants had ever suppressed to <1000 copies/mL
(p=0.009)
• Infants took longer to achieve partial suppression
(median 159 days vs. 91 days among children,
p=0.0075)
data not shown
• There was no difference in time to partial suppression
among infants by PI vs. NNRTI regimen (p=0.37)
Ásbjörnsdóttir KH, Hughes JP, Wamalwa D, et al. Differences in virologic and immunologic
response to antiretroviral therapy among HIV-1-infected infants and children. AIDS.
2016;30(18):2835‐2843. doi:10.1097/QAD.0000000000001244
11
OPH + PAD Cohorts: Study Design
Optimizing Pediatric HIV Therapy (OPH) & Pediatric
Adherence (PAD) longitudinal cohorts 2004-2010, Kenya

12. Mwango Albert, MDHIVCLINICAL UPDATE
Viral suppression (<1000c/mL)
• During the first two years following ART
initiation:
• After 2yrs more Children (>13 months of age) than
Infants achieved “partial” suppression (<1000c/ml)
• By 24 months on ART, 93% of children and 81% of
infants had ever suppressed to <1000 copies/mL
(p=0.009)
• Infants took longer to achieve partial suppression
(median 159 days vs. 91 days among children,
p=0.0075)
data not shown
• There was no difference in time to partial suppression
among infants by PI vs. NNRTI regimen (p=0.37)
Ásbjörnsdóttir KH, Hughes JP, Wamalwa D, et al. Differences in virologic and immunologic
response to antiretroviral therapy among HIV-1-infected infants and children. AIDS.
2016;30(18):2835‐2843. doi:10.1097/QAD.0000000000001244
12
OPH + PAD Cohorts: Study Design
Optimizing Pediatric HIV Therapy (OPH) & Pediatric
Adherence (PAD) longitudinal cohorts 2004-2010, Kenya

13. Mwango Albert, MDHIVCLINICAL UPDATE
Viral suppression (<1000c/mL)
• During the first two years following ART
initiation:
• After 2yrs more Children (>13 months of age) than
Infants achieved “partial” suppression (<1000c/ml)
• By 24 months on ART, 93% of children and 81% of
infants had ever suppressed to <1000 copies/mL
(p=0.009)
• Infants took longer to achieve partial suppression
(median 159 days vs. 91 days among children,
p=0.0075)
data not shown
• There was no difference in time to partial suppression
among infants by PI vs. NNRTI regimen (p=0.37)
Ásbjörnsdóttir KH, Hughes JP, Wamalwa D, et al. Differences in virologic and immunologic
response to antiretroviral therapy among HIV-1-infected infants and children. AIDS.
2016;30(18):2835‐2843. doi:10.1097/QAD.0000000000001244
13
OPH + PAD Cohorts: Study Design
Optimizing Pediatric HIV Therapy (OPH) & Pediatric
Adherence (PAD) longitudinal cohorts 2004-2010, Kenya

14. Mwango Albert, MDHIVCLINICAL UPDATE
Viral suppression (<1000c/mL)
• During the first two years following ART
initiation:
• After 2yrs more Children (>13 months of age) than
Infants achieved “partial” suppression (<1000c/ml)
• By 24 months on ART, 93% of children and 81% of
infants had ever suppressed to <1000 copies/mL
(p=0.009)
• Infants took longer to achieve partial suppression
(median 159 days vs. 91 days among children,
p=0.0075)
data not shown
• There was no difference in time to partial suppression
among infants by PI vs. NNRTI regimen (p=0.37)
Ásbjörnsdóttir KH, Hughes JP, Wamalwa D, et al. Differences in virologic and immunologic
response to antiretroviral therapy among HIV-1-infected infants and children. AIDS.
2016;30(18):2835‐2843. doi:10.1097/QAD.0000000000001244
14
OPH + PAD Cohorts: Study Design
Optimizing Pediatric HIV Therapy (OPH) & Pediatric
Adherence (PAD) longitudinal cohorts 2004-2010, Kenya

15. Mwango Albert, MDHIVCLINICAL UPDATE
Virologic Outcomes in children in Macha Zambia
• A prospective cohort study
• HIV-infected children, <16 yrs
• Sept 2007 and Sept 2010
• In a rural HIV clinic (Macha, Zambia)
• Method
• Children started on ART when ART eligible
• Group A – already on ART
• Group B –treatment naive
• Followed up and reported treatment outcomes
after two years
• End points
• mortality, immunologic status, and virologic
suppression, and risk factors
van Dijk et al, 2011
15

16. Mwango Albert, MDHIVCLINICAL UPDATE
Routine Viral Load Monitoring – Pediatrics (<15 years)
6 months
12 months
18 months
Then every
12 months if
suppressed
NEW
ZCG 2020
RECOMMENDATION
16

17. Mwango Albert, MDHIVCLINICAL UPDATE
Key slides from w.02
17

18. Mwango Albert, MDHIVCLINICAL UPDATE
Take home from previous discussions
• We reviewed:
• The recommended choices of regimens for CLHIV
• Preferred first line (FL) regimens in CLHIV (with /without Rif – ATT)
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19. Mwango Albert, MDHIVCLINICAL UPDATE
Recommended Regimen for FL in treatment naïve CLHIV
• a dual- NsRTI/NtRTI backbone plus an
InSTI, or PI-r or a NNRTI (anchor drug)
19
NsRTI NtRTIOR
InSTI, or PI-r or a NNRTI
PLUS
Backbone
Anchor Drug

20. Mwango Albert, MDHIVCLINICAL UPDATE
Recommended Regimen for FL in treatment naïve CLHIV
• a dual- NsRTI/NtRTI backbone
plus an InSTI, or PI-r or a
NNRTI* (anchor drug)
20
NsRTI NtRTIOR
InSTI, or PI-r or a NNRTI
PLUS
Backbone
Anchor Drug

21. Mwango Albert, MDHIVCLINICAL UPDATE
Preferred FL Regimens for CLHIV in Zambia, ZCG 2020
Treatment Naïve no Anti-TB Rx
• <3kgAZT+3TC+NVP
• 3- <20kgABC+3TC+LPV-r
• 20- <25kgABC+3TC+DTG
• 25+ kgTAF+FTC+DTG
21
<3kg 3kg 20kg 25kg 30kg
TLD
TafED
LPV-r
NVP

22. Mwango Albert, MDHIVCLINICAL UPDATE
Preferred FL Regimens for CLHIV with TB
in Zambia, ZCG 2020
Treatment Naïve with Anti-TB Rx
(rifampicin based)
22
• <20kg
ABC+3TC+RAL*
OR
ABC+3TC+AZT
• 20-
<30kg
ABC+3TC+DTG*
• 30+ kgTDF+3TC+DTG*
<3kg - <20kg 20kg- <30kg 30kg
RAL* or Triple Nukes
DTG*
TLD *
*double frequency of DTG/RAL
TB/HIV

23. Mwango Albert, MDHIVCLINICAL UPDATE
Basics for managing suspected treatment
failure
23

24. Mwango Albert, MDHIVCLINICAL UPDATE
Normal Variance and Significant Viral Loads Change
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• Patients with acute HIV-1 infection typically have VL between
250,000 and 9.5 million c/mL
• Viral Load change of +/- 0.3 log10 (x2) is considered due to
biological/physiologic changes (Hughes et al, 1997)
• Significant VL change
• 0.7 log10 (x5) children <2 yrs
• 0.5 log10 (x3) children >2 yrs
https://doi.org/10.7326/0003-4819-126-12-199706150-
00001

25. Mwango Albert, MDHIVCLINICAL UPDATE
Limitations of VL testing
• Only 2% of the HIV is in the blood
• HIV-1 in the tissues/organs –lymph nodes, spleen or brain
cannot be measured using standard VL tests
• VL is higher when fighting an infection or just after
immunizations
• Do not take blood for VL testing within 4 weeks of any infection or
immunization
25

26. Mwango Albert, MDHIVCLINICAL UPDATE
What is a blip?
26
• Blips 50 to >200 c/ml
• Frequent VL testing every 3 months
• Occasional blips do not mean treatment is failing
• Frequent blips are a risk of failure – esp. >500c/ml
• Immune system under stress (illness) or
• missing doses

27. Mwango Albert, MDHIVCLINICAL UPDATE
Definition of Viralogic Failure
• Is a persistently detectable VL >1000 copies/mL
• Two consecutive viral load measurements within a 3-month
interval
• With adherence support between measurements
• After at least 6 months of starting a new ART regimen
• An individual must be taking ARVs for at least 6 months
before it can be determined that a regimen has failed

28. Mwango Albert, MDHIVCLINICAL UPDATE
Virologic Failure
• Provide EAC is VL is
>1000c/mL
• Duration can vary but it
should be structured
• If re-test VL after 3
months is still >1000c/mL
consider switching
28

29. Mwango Albert, MDHIVCLINICAL UPDATE
Enhanced Adherence Counselling (EAC)

30. Mwango Albert, MDHIVCLINICAL UPDATE
Causes of Pediatric Treatment Failure
Probe for:
1. Correct dosing
2. Efficacious regimen
3. Correct time
4. Correct frequency
5. Adequate supply (sharing, lost meds)
6. Correct instructions
7. Disclosure
8. New relationship
9. Social economic difficulties
“Probe” Brainstorm“Cause” Brainstorm

31. Mwango Albert, MDHIVCLINICAL UPDATE
Causes of Pediatric Treatment Failure
Probe for:
1. Correct dosing
2. Efficacious regimen
3. Correct time
4. Correct frequency
5. Adequate supply (sharing, lost meds)
6. Correct instructions
7. Disclosure
8. New relationship
9. Social economic difficulties
“Probe” Brainstorm

32. Mwango Albert, MDHIVCLINICAL UPDATE
Causes of Pediatric Treatment Failure
Probe for:
1. Correct dosing
2. Efficacious regimen
3. Correct time
4. Correct frequency
5. Adequate supply (sharing, lost meds)
6. Correct instructions
7. Disclosure
8. New relationship
9. Social economic difficulties

33. Mwango Albert, MDHIVCLINICAL UPDATE
omadahealth.com
It is not just “IF” a Patient is non adherent but “WHY”?

34. Mwango Albert, MDHIVCLINICAL UPDATE
Process of Enhanced Adherence Counselling

35. Mwango Albert, MDHIVCLINICAL UPDATE
Process of Enhanced Adherence Counselling

36. Mwango Albert, MDHIVCLINICAL UPDATE
Interventions
Approach Intervention
Education and counselling 1. Fast track counselling
2. EAC for unstable patients
3. Disclosure counselling for CLHIV
Repeat prescription collection strategies 4. Adherence clubs
5. Spaced and fast lane appointments
6. Decentralized medication delivery
Patient tracing 7. Early tracing of all missed appointments
Integrated HIV, TB, NCD care 8. Integrated consultation and counselling

37. Mwango Albert, MDHIVCLINICAL UPDATE
How effective is EAC?
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38. Mwango Albert, MDHIVCLINICAL UPDATE
% of patients with an initial elevated viral load
who re-suppress following EAC
• Overall less than half (46%) re-suppressed
• SL re-suppressed > FL
• Adult re-suppressed >Adolescents > children
• 1/3 of children re-suppressed
Ford N, Orrell C, Shubber Z, Apollo T, Vojnov L. HIV viral resuppression
following an elevated viral load: a systematic review and meta-analysis. J
Int AIDS Soc. 2019;22(11):e25415. doi:10.1002/jia2.25415

39. Mwango Albert, MDHIVCLINICAL UPDATE
Second Line
ART:
Children &
PBFW
Zambia Consolidated
Guidelines 2020

40. Mwango Albert, MDHIVCLINICAL UPDATE
Second Line
ART:
Adolescents &
Adults
Zambia Consolidated
Guidelines 2020

41. Mwango Albert, MDHIVCLINICAL UPDATE
Zambia Consolidated
Guidelines 2020
Dosing (1)

42. Mwango Albert, MDHIVCLINICAL UPDATE
Dosing (2)
Zambia Consolidated
Guidelines 2020

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44. Mwango Albert, MDHIVCLINICAL UPDATE 44