Treatment failure
diagnosis and
management
June/2022
Revised treatment monitoring with viral
load testing
1. Viral suppression: is a viral load that is undetectable, equal to or less
than 50 copies/ ml.
2. Low-level viraemia: Viral load results that are detectable (more than
50 copies/ ml) but equal to or less than 1000 copies/ml.
3. Virological failure: Viral load above 1000 copies/ml based on two
consecutive viral load measurements in 3 months, apart with enhanced
adherence support following the first viral load test.
Revised treatment monitoring with viral
load testing
• Those with low-level viraemia at the first viral load test (50–1000
copies/ml) need to be provided with enhanced adherence support
(EAS) and repeat viral load test after 3 months to promote viral
suppression. If viral load is still 50-1000 copies/ml, maintain ARV
drug regimen and continue viral load test every six months.
• In addition, continue the routine follow up support and link to
community-based adherence support services.
Viral load is the best measure of treatment
response
TIME
Poor Virological Immunological Clinical
Adherence Failure- VL Failure – CD4 Failure:
(Predictor of specific
TF)
illnesses
Earliest indicator – tells us if the virus is replicating
Type of treatment failure
Type of Definition Remark
failure
Adults and adolescents o The condition must
New or recurrent clinical event indicating severe be differentiated
immunodeficiency (WHO clinical stage 4 condition and from immune
Clinical certain WHO clinical stage 3 conditions (pulmonary TB
and severe bacterial infections) may also indicate
reconstitution
failure treatment failure) after 6 months of effective treatment.
inflammatory
syndrome occurring
Children after initiating ART
New or recurrent clinical event indicating
advanced or severe immunodeficiency(WHO
clinical stage 3 and 4 clinical condition with
exception of TB) after 6 months of effective
treatment.
Type of failure Definition Remark
Adults and adolescents o Without concomitant or
CD4 count at or below 250 recent infection to cause a
cells/mm3 following clinical transient decline in the
failure or CD4 cell count.
Persistent CD4 levels o Persistent is to mean at
Immunologic failure below 100 cells/mm3. least 2 CD4 measurements
below the threshold.
Current WHO clinical and
immunological criteria
Children
Younger than 5 years have low sensitivity and
positive predictive value
Persistent CD4 level below
for identifying individuals
200 cells/mm3 or <10%
Older than 5 years with virological failure
Persistent CD4 levels below
100 cells/mm3.
Type of failure Definition Remark
Viral load above 1000 o An individual must be
copies/ml based on two taking ART for at least 6
Virological consecutive viral load months before it can be
failure measurements in 3 months, determined that a
with enhanced adherence regimen has failed.
support following the first o VL testing should not be
viral load test done when there is an
acute infection/fever.
Enhanced adherence counseling should be started on the day the
result is given
• By the clinicians and pharmacists
• By the counselors (Case manager, Adherence worker and
Mather support group)
The reasons for High Viral Load that Need Investigation may be due
to:
Medical factors
Psychosocial factors
Medical Reasons for High Viral load
1. Drug interactions causing sub therapeutic levels of
ARVs (any enzyme inducing drug e.g. rifampicin,
traditional medicines, antiepileptic )
2. Inadequate absorption E.g. chronic diarrhoea or
vomiting)
3. Side effects-
4. Previous exposure to ART - resulting in primary
resistance
5. Any defaulter
6. Not changing the ARV dose with weight change in
pediatric age group(under dose )
Psychosocial Reasons for High Viral Load
Cognitive barriers: Awareness, perception & knowledge
Socio-economic barriers: lack of social support, lack of
disclosure, stigma, poor living condition, lack of food, money
for transport,…..
Behavioural barriers: attitude, motivation, confidence & skills
Psychological/Emotional barriers: common mental disorders
including-anxiety, depression, substance abuse, psychosis, …
What is EAS ?
EAS is a continual and repeated process that involves:
Step 1: A structured
assessment of current
level of adherence
Step 4: Develop Step 2: Explore the
individualized specific barriers the
adherence intervention patient must
plan overcome
Step 3: Motivating and assisting
patients to identify solutions and
address barriers
Repeat Steps: 3-6 months follow-up sessions.
Why do EAS for HVL clients?
VL is not just a monitoring tool to switch patients correctly to 2 nd /3rd
line – it is also helping people to stay on 1 st line with good health
A recent systematic review showed that on average, 70.5% have a re-
suppressed viral load after a targeted enhanced adherence intervention
Guidance for changing ARV regimens for treatment failure
Avoid premature as well as delayed switching of
ART
• Assess adherence and address barriers.
• Assess for and Address drug interaction issues.
• Do not add one drug to a failing regimen.
• Consider resistance and cross resistance
patterns.
• Get advice from experienced clinicians.
• At least two new drugs.
• Preferably one new drug class.
Management of first-line treatment failure (switching to
second-line ART)
• Using a boosted PI + two NRTI combinations is recommended as the
preferred strategy for second-line ART for adults, adolescents, and
children.
• Two NRTI + DTG can be used as second line regimen if it is not used
in the first line.
Monitoring after switching
Clients who are on Second line drug Should be instructed well on
adherence and the possible symptoms of toxicities related to second
line ART drugs
Monitoring after switching…
• Patients who are on second-line regimen and have high viral load
level(>1000copies/ml) after 6 months of treatment need to go
through the algorithm as described for first line treatment failure with
EAS and
• Repeat test after three months to decide second line treatment
failure.
• Once patients are confirmed to have second line failure they should
be referred to hospital for third line drug
Management of 2nd line treatment failure in adults & pediatrics
Treatment failure is indicated by virological non-suppression with or without
immunologic and/or clinical deterioration.
Doctors and nurses should participate directly in the adherence assessments, and
do not delegate the assessment to the adherence counselor alone
• Before switching to third line regimen, health care providers should
ensure the following:
o Two consecutive viral load measurements > 1000 copies/ml at least 3
months apart.
o First viral load measurement done at least 6 months after switching to
second-line regimen.
o The repeat viral load test should be done after 3 months of enhanced
adherence support.
Summary of sequencing options for preferred first, second and third-line ART
regimens in adults
Summary of sequencing options for
preferred first, second and third-line ART
regimens in adults
Management of 2nd line treatment failure
• DRV/r has a higher genetic barrier to resistance compared to early-generation
PIs and is active against multidrug-resistant HIV isolates and it has been
demonstrated to be cost-effective compared to other boosted PIs.
• Ritonavir is a booster for other protease inhibitors such as LPV, ATV and DRV
• In PI-experienced patients, the recommended DRV/r dose should be 600mg/100
mg twice daily.
• DRV must be administered with 0.5ml of RTV 80mg/mL oral suspension if the
child weighs less than 15kg and with RTV 50mg solid formulation for children
weighing 15–30kg.
• DRV/r should not be used in children younger than three years of age
aFor individuals with no previous use of protease inhibitors.
•b For individuals with previous use of protease inhibitors.
Monitoring response to third line ART service
• Clients after starting third line ARVs shall be appointed within two weeks of
initiation for close follow up.
• Monthly clinical and laboratory Screening for opportunistic infections and
drug side effects in the first six months
• The client should receive enhanced adherence support for the first six
months
• Senior physicians and nurses should directly do adherence support to
clients on third line ART; they should not leave to case managers/
adherence supporters alone.
• Routine viral load monitoring should be carried out at six months, at 12
month and then every 12 months thereafter.
Thank you
