How to Escape from

Pitfalls in ARV Treatment

DINA MUKTIARTI
HIV Task Force Indonesia Pediatric Society
Department of Child Health
Faculty of Medicine Universitas Indonesia-
Cipto Mangunkusumo Hospital
TOPICS

01 BACKGROUND

02 PITFALLS IN GIVING ARV

HOW TO ESCAPE FROM PITFALLS IN ARV TREATMENT -
03
UPDATE ON ARV TREATMENT
04 CONCLUSIONS
Double (Triple) Burden Pediatric HIV in
Indonesia

Vertically-infected HIV
Vertically-infected HIV
adolescents are
children still persist
increasing

+ Horizontal transmitted HIV

children
Antiretroviral treatment
PITFALLS IN GIVING ARV
• Deferred ARV initiation
• Wrong dose
• Wrong formula
• Not consider drug interaction
• No education
• No monitoring
HOW TO ESCAPE FROM PITFALLS IN
ARV TREATMENT - UPDATE ON ARV
TREATMENT
UPDATE ON ARV TREATMENT

Who Why When

What Where How

ARV management

WHO
• Children with HIV infection
WHY
• Maximally and durably suppressing viral
replication
• Restoring and/or preserving immune function
as reflected by CD4 cell measures
• Preventing emergence of viral drug-resistance
mutations
• Minimizing drug-related toxicity
• Maintaining normal physical growth and
neurocognitive development
• Reducing HIV-related mortality and morbidity
• Improving quality of life.
 ARV management - WHEN
WHO 2010 WHO 2013
When
Deferred
x ARV initia

WHO 2016
tio n
PNPK
2019
Clinical stage 3 ALL ALL ALL ALL
or 4
• Treat all HIV-infected
0-12 months ALL childrenALL(not depend on ALL HIV stage
ALL
ormonths
12-24 CD4 level). ALL ALL ALL ALL
24-59 months CD4+ ≤750 cells/mm or
3 ALL ALL ALL
• Treat opportunistic ≤ 25% infection
Priority: such
CD4+ ≤350as TB Priority:
for 2CD4+ weeks
≤750
cells/mm cells/mm
before ARV initiation – no need to wait untilALL
3 3

5-10 years old CD4+ ≤350 cells/mm 3 CD4+ ≤500 cells/mm 3 ALL
management of IO is completed. Priority: CD4+ ≤350
cells/mm3
Priority: CD4+ ≤350
cells/mm 3

• Patient/family/caregiver
10-19 years old CD4+ ≤350 cells/mm 3
ready
CD4+ ≤500 cells/mm 3 ALL ALL
Priority: CD4+ ≤350 Priority: CD4+ ≤350
cells/mm3 cells/mm3
 Protease inhibitors chromosome of in
1995 Saquinavir capability to be ac
1996 Ritonavir new infective viral p

ARV management - WHAT

1996 Indinavir Reverse transcri
1997 Nelfinavir
retrovirus-encoded
2000 Lopinavir (/r)
for the production
2003 Atazanavir (/r, /c)
proviral DNA from
2003 Fosamprenavir
genomic RNA.
2005 Tipranavir (/r)

Antiretroviral drugs
2006 Darunavir (/r, /c) Viral load: term u
Receptor
binding and quantity of genetic
entry RNA, of a virus pre
Usually, in HIV-infe

and HIV replication

A!achment Maturation
inhibitors measurement is gi
coreceptor copies per ml of p
antagonists Virological suppr

cycle
Assembly
2007 Maraviroc gp120-
and HIV-infected individ
gp41
budding achievement of co
2018 Ibalizumab-uiyk
2020 Fostemsavir viral replication, me
Env
plasma as less tha
Reverse
copies/mL.
Fusion
Gag
ssRNA transcription
inhibitors Gag-Pol

2003 Enfuvirtide
dsDNA

Reverse
transcriptase Integration
inhibitors
NRTIs 1987 Zidovudine (AZT)
1991 Didanosine
1992 Zalcitabine
Integrase inhibitors
1994 Stavudine 2007 Raltegravir
1995 Lamivudine 2012 Elvitegravir (/c)
Abbreviations: AZT, azidothymidine; /c, boosted 1998 Abacavir 2013 Dolutegravir
2001 Tenofovir (TDF, TAF) 2018 Bictegravir
with cobicistat; NRTI, nucleoside reverse 2003 Emtricitabine 2021 Cabotegravir
transcriptase inhibitors; NNRTI, non-nucleoside NNRTIs 1996 Nevirapine
reverse transcriptase inhibitors; /r, boosted with 1997 Delavirdine
1998 Efavirenz
ritonavir; TAF, tenofovir alafenamide; TDF, 2008 Etravirine
2011 Rilpivirine
tenofovir disoproxil fumarate. 2018 Doravirine
Menéndez-Arias L, Delgado R. Trends
Trends inPharmacol Sci. 2022;43:16-29
Pharmacological Sciences
 ACCEPTED MANUSCRIPT
55

ARV: Potency and Genetic Barrier to Resistance

Figure 1. ARV potency versus genetic barrier to resistance.

PT
RI
SC
NU
MA
T ED
EP

Clutter DS, dkk. Infect Genet Evol. 2016;46:292-307.

ARV management - WHAT

Backbone: One of:

2 nucleoside • integrase strand transfer inhibitor (INSTI)
reverse + • non-nucleoside reverse transcriptase inhibitor
transcriptase (NNRTI)
inhibitors (NRTIs) • boosted protease inhibitor (PI)

US Guidelines for the Use of Antiretroviral Agents in Pediatric HIV Infection, 2022
Antiretroviral Drug

NRTI (nucleotide/nucleoside reverse-transcription inhibitor)

• Zidovudine (100 mg, 300 mg), Abacavir (300 mg), Tenofovir (TDF, 300 mg), Lamivudine (150
mg)
• FDC: Zidovudine/Lamivudine 300/150mg; Abacavir/Lamivudine (dispersible tablet) 120/60 mg
NNRTI (non-nucleotide reverse-transcriptase inhibitor)
• Nevirapine (200 mg), Evafirenz (200 mg, 600 mg)
• FDC: Tenofovir/Lamivudine/Efavirenz (TLE) 300/300/600 mg
PI (Protease Inhibitor)
• Lopinavir/ritonavir (Aluvia – capsul 200/50 mg, 100/25 mg), Alltera – granul 40/10 mg/sachet)
INSTI (Integrase Inhibitor)
• Dolutegravir (10 mg, 50 mg)
• FDC: Tenofovir/Lamivudine/Dolutegravir (TLD) 300/300/50 mg
Zidovudin 100 mg Zidovudin 300 mg/lamivudin 150 mg Nevirapin 200 mg

Efavirez 600 mg Efavirenz 200 mg Lamivudin 150 mg

Courtesy: UPT HIV RSCM, Child Health Department FKUI/RSCM
 Abacavir 120 mg/
lamivudine 60 mg

Abacavir 300 mg
Lopinavir 100 mg/
ritonavir 25 mg

Lopinavir 40 mg/
ritonavir 10 mg

Lopinavir 200 mg/

ritonavir 50 mg Lopinavir 200 mg/
ritonavir 50 mg
Courtesy: UPT HIV RSCM, Child Health Department FKUI/RSCM
 Tenofovir disproksil fumarat 300 mg/
Tenofovir disproksil fumarat 300 mg/
Tenofovir disproksil fumarat 300 mg Lamivudin 300 mg/Efavirenz 600 mg
Emtricitabin 200 mg

Tenofovir disproksil fumarat 300 mg/

DO NOT Lamivudin 300 mg/Dolutegravir 50 mg
CRUSH THE
TABLET

Dolutegravir 50 mg
Courtesy: UPT HIV RSCM, Child Health Department FKUI/RSCM
Dolutegravir

• Dolutegravir is a new, second-generation integrase strand-

transfer inhibitor (INSTI) that has been approved for the
treatment of HIV-1 infection.
• Advantages:
• Highly active against wild-type and drug-resistant virus
• Once daily
• Drug interaction: Rifampicin will decrease DTG 50%

Rathburn RC, dkk. Ann Pharmacother. 2014;48:395-403

 The n e w e ng l a n d j o u r na l of m e dic i n e

Difference in Proportion of Participants

Time Point Dolutegravir Standard Care with Treatment Failure (95% CI)
no. of participants with treatment Noninferiority margin, Noninferiority margin
failure (estimated probability) overall for cohorts (A and B)
Wk 48
Total 20 (0.06) 42 (0.12) −0.06 (−0.10 to −0.02)
ODYSSEY A 9 (0.06) 20 (0.13) −0.07 (−0.13 to −0.01)
ODYSSEY B 11 (0.06) 22 (0.11) −0.05 (−0.11 to −0.004)
Wk 96
Total 47 (0.14) 75 (0.22) −0.08 (−0.14 to −0.03)
ODYSSEY A 15 (0.10) 34 (0.22) −0.12 (−0.21 to −0.04)
ODYSSEY B 32 (0.16) 41 (0.21) −0.05 (−0.12 to 0.03)
ODYSSEY A: participants who were Wk 144
starting first-line antiretroviral Total 56 (0.17) 87 (0.27) −0.09 (−0.16 to −0.04)
therapy (ART). ODYSSEY A 19 (0.13) 36 (0.25) −0.12 (−0.21 to −0.03)
ODYSSEY B 37 (0.21) 51 (0.28) −0.08 (−0.16 to 0.01)
ODYSSEY B: participants who were
−0.24 −0.20 −0.16 −0.12 −0.08 −0.04 0.00 0.04 0.08 0.12
starting second-line ART after having
treatment failure. Dolutegravir Better Standard Care Better

Difference in the Proportion of Participants with Virologic or

Figure 1. Difference in the Proportion of Participants with Virologic or Clinical Treatment Failure by 48, 96, and 144 Weeks.
Turkova A, dkk. N Engl J Med 2021;385:2531-43. Clinical Treatment
The primary end point was treatment failure by 96 weeks.Failure bypresented
Results are 48, 96, both
and overall
144 Weeks
and according to trial
 wnloaded from https://onlinelibrary.wiley.com/doi/10.1002/jia2.25970 by INASP/HINARI - INDONESIA, Wiley Online Library on [06/12/2022]. See the Terms and Conditions (https://onlinelibrary.wiley.com/terms-and-conditions)
http://onlinelibrary.wiley.com/doi/10.1002/jia2.25970/full | https://doi.org/10.1002/

from https://onlinelibrary.wiley.com/doi/10.1002/jia2.25970 by INASP/HINARI - INDONESIA, Wiley Online Library on [06/12/2022]. See the Terms and Conditions (https://onlinelibrary.wiley.com/terms-an
17582652, 2022, 11, Downloaded from https://onlinelibrary.wiley.com/doi/10.1002/jia2.25970 by INASP/HINARI - INDONESIA, Wiley Online Library on [06/12/2022]. See t
25970
rg/10.1002/jia2.25970

Figure 3. Proportion of infants, children and adolescents achieving viral suppression of <50 copies/ml (open symbols), or <400 copies/ml,
<1000 copies/ml or viral suppression at an unspecified threshold if <50 copies/ml was not reported (shaded symbols) after treatment
re 3.with
Proportion of infants,
(a) dolutegravir children
or (b) andover
raltegravir adolescents achieving
time. Results viral suppression
are stratified of <50
by age (colour copies/ml
of symbol), line (open symbols),
of therapy (shapeorof<400 copies/ml,
symbol) and
00 copies/ml or viral suppression at an unspecified threshold if <50 copies/ml was not reported (shaded symbols)
study size (size of symbol). Connecting lines link data follow-up points from the same study population. Data from an individual study after treatment
h (a) may
dolutegravir or (b)at raltegravir
be presented more than oneovertimepoint;
time. Results are at
however, stratified
a given by age (colour
timepoint, of symbol),
data from a group line of therapy
of subjects (shape
are only of symbol)
presented once and
dy size (size data
(overall of symbol). Connecting
were prioritized over lines link data).
sub-group data follow-up points
For randomized from the
controlled same
trials andstudy population.
single-arm studies, Data from anrepresents
the timepoint individualthe
study
be presented at more than one timepoint; however, at a given timepoint, data from a group of subjects are only presented once
duration of follow-up; for observational studies, the timepoint represents the median follow-up time of the study. A table showing the
viral were
rall data load data used to over
prioritized createsub-group
the scatterplot
data).isFor
included in File S2
randomized Proportion of infants, children and adolescents achieving
(Table S2).trials and single-arm studies, the timepoint represents the
controlled
viral suppression (8 studies, 1281 subjects)
ation of follow-up; for observational studies, the timepoint represents the median follow-up time of the study. A table showing the
l load data used to create the scatterplot is included in File S2 (Table S2).
(follow-up to 144 weeks in IMPAACT P1093, 24 weeks in for up to 1 year, and the study was considered high risk of
ODYSSEY pharmacokinetic sub-study and up to 43 weeks in bias.
Bacha 2020) [19, 25, 28, 30, 31] (Figure 4). One discontin- Total cholesterol data in children and adolescents were
What – New Guideline
PMK No. 23 Th 2022 tentang Penanggulangan HIV, AIDS dan
Infeksi Menular Seksual

Rekomendasi Terapi ARV Lini Pertama

Paduan terapi ARV lini pertama pada remaja
Paduan pilihan TDF+3TC+DTG
Paduan alternatif TDF+3TC+EFV600
TDF+3TC+EFV400
Paduan terapi ARV lini pertama pada remaja dengan koinfeksi TB
Paduan pilihan TDF+3TC+EFV600
Paduan alternatif TDF+3TC+DTG dengan penambahan 1 tablet
DTG 50 mg dengan jarak 12 jam
What – New Guideline
PMK No. 23 Th 2022 tentang Penanggulangan HIV, AIDS dan
Infeksi Menular Seksual
Paduan terapi ARV lini pertama pada anak usia 3-10 tahun
Paduan pilihan AZT+3TC+EFV

Paduan alternatif ABC+3TC+EFV

ABC+3TC+DTG
AZT+3TC+DTG
TDF+3TC (atau FTC)+EFV
TDF+3TC (atau FTC)+DTG
Paduan terapi ARV lini pertama pada anak < 3 tahun
Paduan pilihan (ABC atau AZT)+3TC+LPV/r*

Paduan alternatif (ABC atau AZT)+3TC+DTG**

(ABC atau AZT)+3TC+NVP (untuk bayi <2-4 minggu, setelah
mencapai usia ≥2-4 minggu dapat switch ke LPV/r atau DTG)
*LPV/r untuk bayi usia kronologis ≥2 minggu dan usia gestasi ≥42 minggu
**DTG untuk bayi usia kronologis ≥4 minggu dan BB ≥3 kg
 ARV Dose
Table A1.1 Simplified dosing of child-friendly fixed-dose solid formulations for twice-daily dosing for infants
and children four weeks and oldera
Drug Strength of Number of tablets by weight band morning and evening Strength of Number of tablets by
paediatric tablets adult tablet weight band
3–<6 kg 6–<10 kg 10–<14 kg 14–<20 kg 20–<25 kg 25–<35 kg
AM PM AM PM AM PM AM PM AM PM AM PM
AZT/3TC Tablet (dispersible) 1 1 1.5 1.5 2 2 2.5 2.5 3 3 300 mg/150 mg 1 1
60 mg/30 mg
ABC/3TC Tablet (dispersible) 1 1 1.5 1.5 2 2 2.5 2.5 3 3 600 mg/300 mg 0.5 0.5
60 mg/30 mgb
Tablet (dispersible)
120 mg/60 mg ✓ 0.5 0.5 0.5 1 1 1 1 1.5 1.5 1.5 600 mg/300 mg 0.5 0.5

a
For infants younger than four weeks old, see Table A1.4 for more accurate dosing, which is reduced because of the decreased ability to excrete and metabolize medications. For infants who are at
least four weeks old but weigh less than 3 kg, the immaturity of renal and hepatic pathways of elimination are less of a concern, but uncertainty still exists on the appropriate dosing of ARV drugs for
preterm and low-birth-weight infants.
b
This formulation will be phased out of use over time, and programmes should transition to using the 120 mg/60 mg dispersible scored tablets.

WHO, 2021
Table A1.3 Simplified dosing of child-friendly solid and oral liquid formulations for twice-daily dosing for
infants and children four weeks of age and oldera
Drug

Solid formulations
Strength of
paediatric tablets

AM
3–<6 kg
PM
Wrong do

6–<10 kg
AM PM
W
Number of tablets or mL by weight-band morning (AM)rand

10–<14 kg
AM PM
onevening
se
g for(PM)
mula
14–<20 kg
AM
x
PM
20–<25 kg
AM PM
Strength of
adult tablet
Number of tablets
by weight band

AM
25–<35 kg
PM

AZT Tablet (dispersible) 1 1 1.5 1.5 2 2 2.5 2.5 3 3 300 mg 1 1

60 mg
ABC Tablet (dispersible) 1 1 1.5 1.5 2 2 2.5 2.5 3 3 300 mg 1 1
60 mg
LPV/rb Tablet 100 mg/25 mg
Pellets 40 mg/10 mg
✓ –
2
–
2
–
3
–
3
2
4
1
4
2
5
2
5
2
6
2
6
– 3
–
3
–

✓
Granules 40 mg/10 mg 2 2 3 3 4 4 5 5 6 6 – –
Table A1.2 Simplified
sachet
dosing of child-friendly solid formulations for once-daily dosing for infants and children
four weeks and oldera (continued)
DRV c
Tablet 75 mg – – – – – – 5 5 5 5 400 mg 1 1
Drug
RTVd Strength of 25
Tablet paediatric
mg tablet – – Number
– of tablets
– or–capsules
– by weight
2 band2 once daily
2 2 Strength
100 mg of Number
1 of tablets
1 or
adult tablet capsules by weight
Tablet 50 mg – – – – – – 1 1 1 1
band once daily
RALe Chewable tablets 1 1 2 2 3 3 4 4 6 6 400 mg 1 1
3–<6 kg 6–<10 kg 10–<14 kg 14–<20 kg 20–<25 kg 25–<35 kg

✓
25 mg
DTGh Film-coated tablet 50 mg – – – – 1 50 mg 1
Chewable tablets – – – – – – 1 1 1.5 1.5
Dispersible
100 mgtablet 5 mg 1 3 4 5 6
Dispersible scored tablet 10 mg 0.5 1.5 2 2.5 3
a
See Table A1.4 for dosing recommendations for infants younger than four weeks old. Doses for this age group are reduced to account for the decreased ability to excrete and metabolize medications. For infants who
are at least four weeks old but weigh less than 3 kg, immaturity of renal and hepatic pathways of elimination are less of a concern, but uncertainty still exists on the appropriate dosing of ARV drugs for preterm and
low-birth-weight infants. WHO, 2021
b
EFV is not recommended for children younger than three years and weighing less than 10 kg.
c
 Colour legend

Drug Interaction
These drugs should not be co-administered
Potential clinically significant interaction that is likely to require additional monitoring,
alteration of drug dosage or timing of administration
Potential interaction likely to be of weak intensity. Additional action/monitoring or
dosage adjustment is unlikely to be required

Table A2.1 Key drug interactions for ARVs (continued) No clinically significant interaction expected
Numbers indicate further information is available in the footnotes.
ABC FTC 3TC TAF TDF ZDV ATV/r DRV/r LPV/r EFV NVP RPV BIC/FTC/TAF DTG RAL
Kanamycin
Amoxicillin 21
Levofloxacin
Ampicillin 36 36 18
Meropenem
Azithromycin 22 22 18
Bedaquiline
Metronidazole 23
37 24
37 23
38 25
Capreomycin
Moxifloxacin 21 39 2 39 2 18
Cefalexin
Penicillins
Cefixime
Pyrazinamide
Ceftriaxone
Rifabutin 40 41 41 41 42 43
Clarithromycin
Rifampicin 16
40 17 44 26 27 20 28 29 30 19 45 46
Clofazimine
Rifapentine 40 31 31 47 48
No Interaction details
Cycloserine
Spectinomycin
38 No interaction expected with lopinavir/ritonavir
Dapsone
Sulfadiazine 49 tablets.
49 Coadministration
21 is contraindicated
32
14 with lopinavir/ritonavir oral solution. 50
40 Potential decreased exposure of tenofovir alafenamide. However the intracellular tenofovir
Delamanid
Tetracyclines 20 diphosphate
33 (active
20 entity) levels are likely to be higher than those obtained with TDF even
without rifampicin, suggesting that usage of TAF 25 mg QD with rifampicin, rifabutin or rifapentine may be acceptable.
Doxycycline
Trimethoprim/Sulfamethoxazole 32 34 34
44 Coadministration decreased zidovudine exposure. Coadministration is not recommended in the European product label for zidovudine, however, the US product label states that
Ethambutol
Vancomycin
routine dose modification is not warranted. 21 14
45 Ethionamide
Anti-coagulant
Coadministration and Anti-platelet
decreased dolutegravir concentrations. A dose adjustment of dolutegravir to 50 mg twice daily is recommended when coadministered with rifampicin in the absence
of integrase class resistance. In the
Flucloxacillin
Apixaban 35presence of integrase class resistance this combination should be avoided. Dolutegravir
2 502mg twice daily dosing should be maintained for another
2 weeks following cessation of rifampicin due to the persisting inducing effect upon discontinuation of a strong inducer.
 ABC FTC 3TC TAF TDF ZDV ATV/r DRV/r legend
Colour LPV/r EFV NVP RPV BIC/FTC/TAF DTG RAL
Anti-diabetics These drugs should not be co-administered
Potential clinically significant interaction that is likely to require additional monitoring,
Glibenclamide (Glyburide) 1 1 1 2 2
alteration of drug dosage or timing of administration

Drug Interaction
Gliclazide 2 2 2 interaction
Potential 1 likely to be of weak intensity. Additional action/monitoring or
dosage adjustment is unlikely to be required
Insulin
Table A2.1 Key drug interactions for ARVs (continued) No clinically significant interaction expected
Metformin 77
Numbers indicate further information is available in the footnotes. 78
Antifungals ABC FTC 3TC TAF TDF ZDV ATV/r DRV/r LPV/r EFV NVP RPV BIC/FTC/TAF DTG RAL
Anti-diabetics
Amphotericin B 21 32
Glibenclamide
Clotrimazole (Glyburide)
(topical) 1 1 1 2 2
Gliclazide (pessary, troche)
Clotrimazole 2 2 2 1
Insulin
Fluconazole 75 36 36 79 30
Metformin
Flucytosine 80 80 80 32 77
80 78
Antifungals
Itraconazole 16 17 81 82 81 83 19
Amphotericin B
Ketoconazole 16 21
17 32 84 85 86 19
Clotrimazole (topical)
Nystatin
Clotrimazole (pessary, troche)
Voriconazole 87 88 89 90 91
Fluconazole Agents
Antimigraine 75 36 36 79 30
Flucytosine
No Interaction details 80 80 80 32 80
Ergotamine 2
Itraconazole 16 17 81 82 81 83 19
Antiprotozoals
36 No pharmacokinetic interaction expected. However, caution is recommended as both drugs have risks of QT prolongation. ECG monitoring is
Ketoconazole 16 17 84 85 86 19
Amodiaquine recommended. 14 92
Nystatin
75 Coadministration may increase zidovudine exposure. Routine dose modification of 1zidovudine
Artemisinin 1 93is not warranted,
94 95but monitor closely for potential toxicity of
Voriconazole zidovudine. 87 88 89 90 91
Chloroquine 96 96 18 19
79
Antimigraine Coadministration
Agents increased nevirapine exposure by ~100% compared to historical data. Use with caution. Patients should be monitored closely for
nevirapine-associated adverse events.
Ergotamine 2
Antiprotozoals WHO, 2021
Table A1.5 ARV drug dose adjustment for children receiving rifampicin-containing TB treatmenta

x
Drug Strength of Number of tablets or mL by weight-band morning (AM) and evening (PM) Strength of Number of tablets by
paediatric tablets adult tablet weight band

ARV Dose for Patient Consuming Rifampicin

or oral liquid
3–<6 kg 6–<10 kg 10–<14 kg 14–<20 kg 20–<25 kg 25–<35 kg
AM PM AM PM AM PM AM PM AM PM AM PM
DTGb 5 mg dispersible 1 1 3 3 4 4 5 5 6 No6 t con50simg 1 1
tablets de
film-coated r drug int
Table A1.5 ARV
10 mgdrug
scored dose adjustment
0.5 0.5 for
1.5children
1.5 receiving
2 2 rifampicin-containing
2.5 2.5 3 3 TB treatment
tablets a
eraction
dispersible tablets
Drug Strength of Number of tablets or mL by weight-band morning (AM) and evening (PM) Strength of Number of tablets by
50 mg film-coated
paediatric tablets – – – – – – – – 1 1 adult tablet weight band
tablets
or oral liquid
3–<6 kg 6–<10 kg 10–<14 kg 14–<20 kg 20–<25 kg 25–<35 kg
RAL 10 mg/mL 6 mL 6 mL 10 mL 10 mL 16 mL 16 mL 20 mL 20 mL – – 400 mg 2 2
(Oral granules for AM PM AM PM AM PM AM PM AM PM AM PM
DTGb 5suspension: 100 mg/
mg dispersible 1 1 3 3 4 4 5 5 6 6 50 mg 1 1
sachet)
tablets film-coated
Chewable tablets 2 2 4 4 62 62 8 8 –3 –3 tablets
10 mg scored 0.5 0.5 1.5 1.5 2.5 2.5
25 mg
dispersible tablets

✓
Chewable tablets
50 mg film-coated –– –– –– –– –– –– –2 –2 31 31
100 mg
tablets
RAL (with
LPV/r c
Oral solution 80/
10 mg/mL
d
61 mL
mL 61 mL
mL 101.5
mL 101.5
mL 2 mL
16 mL 2 mL
16 mL 202.5
mL 202.5
mL 3 –mL 3 –mL 400–mg –2 –2
additional RTV) 20 mg/mL
(Oral granules for mL mL mL mL
suspension: 100 mg/
Pelletse 40 mg/10 mg 2 2 3 3 4 4 5 5 6 6 – – –
sachet)

✓
Granules 40 mg/10 mg 2 2 3 3 4 4 5 5 6 6 – – –
Chewable
sachet tablets 2 2 4 4 6 6 8 8 – –

✓
25 mg
Tablet 100 mg/25 mg – – – – 2 1 2 2 2 2 100 mg/25 mg 3 3
Chewable tablets – – – – – – 2 2 3 3
100 mg
LPV/rc (with Oral solutiond 80/ 1 mL 1 mL 1.5 1.5 2 mL 2 mL 2.5 2.5 3 mL 3 mL – – WHO,– 2021
additional RTV) 20 mg/mL mL mL mL mL
ARV management

WHERE HOW

• Hospital based • Accurate dose

• Evaluation/monitoring by • Child-friendly formula
pediatrician • On time (every 12 or 24
hours)
• Check for drug interaction
Education before ARV Initiation x
No educa
ti on

• Long life treatment

• Patient should consume ARV on time (every 12/24 hours)
• What to expect
• Side effects
• Monitoring
 148 Consolidated guidelines on HIV prevention, testing, treatment, service delivery and monitoring

Monitoring
Fig. 4.2 Treatment monitoring algorithm updated in 2021

Routine viral load monitoring

for early detection of treatment failure:
obtain and review result by 6 months after
ART initiation, 12 months after ART initiation
and yearly thereafter
x
No monit
o ring

Undetectable Viral load >50 to Viral load >1000

If on NNRTI-based
• Dose adjustment to body
(≤50 copies/ml) ≤1000 copies/ml copies/ml
regimen, switch to weight.
appropriate regimena,b
• Evaluation for growth
Maintain ARV Provide enhanced adherence counselling; and development.
drug regimen repeat viral load testing after 3 monthsc
• Catch up immunization

Undetectable Viral load >50 to Viral load >1000

(≤50 copies/ml) ≤1000 copies/ml copies/ml

Maintain ARV Maintain ARV drug regimen,

Switch to
drug regimen but continue enhanced
appropriate regimen
adherence counselling and
repeat viral load testing after PMK No. 23/2022
3 monthsd
WHO, 2021
Conclusions
• More HIV infected children in Indonesia is surviving after the introduction of ARV
therapy.
• New guideline for 1st line ART in HIV-infected children:
• <3 years old: (ABC/AZT)+3TC+LPV/r
• 3-10 years: AZT+3TC+EFV
• Adolescent: TDF+3TC (or FTC)+DTG
• Avoid pitfalls in ARV treatment with:
• Start ARV initiation for all HIV-infected children ASAP
• Give the right dose
• Give the right formula
• Always consider drugs interactions
• Give education before ARV initiation
• Closely monitoring
THANK YOU