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OPTIMIZING HIV MANAGEMENT IN RESOURCE-LIMITED SETTINGS
MANAGING HIV IN CHILDREN: BEST PRACTICES
Dr. Mo Archary Paediatric Infectious Diseases Specialist University of KwaZulu Natal/ King Edward VIII Hospital
OPTIMIZING HIV MANAGEMENT IN RESOURCE-LIMITED SETTINGS
Overview
Global state of paediatric ART
Filling the gaps in paediatric ART cover
Best practices in paediatric care:
• Diagnosis
• When to start
• What to start
• When to switch
• What to switch to
• How to maintain sustained adherence
OPTIMIZING HIV MANAGEMENT IN RESOURCE-LIMITED SETTINGS
Global State of Paediatric ART
Celebrating successes/Acknowledging failures
OPTIMIZING HIV MANAGEMENT IN RESOURCE-LIMITED SETTINGS
Percentage Decrease Between 2009 and 2011 in the Number of Children (0–14 Years Old) Acquiring HIV Infection in Countries with Generalized Epidemics
UNAIDS report on the global AIDS epidemic 2012. Available at: http://www.unaids.org/en/media/unaids/contentassets/documents/epidemiology/2012/gr2012/20121120_unaids_global_report_2012_with_annexes_en.pdf
Increased
Angola Congo Equatorial Guinea Guinea-Bissau
40–59%
Burundi Kenya Namibia South Africa Togo Zambia
20–39% Botswana Cameroon Côte d’Ivoire Ethiopia Ghana Guinea Haiti Lesotho Liberia Malawi Papua New Guinea Rwanda Sierra Leone Swaziland Uganda Zimbabwe
1–19% Benin Burkina Faso Central African Republic Chad Djibouti Eritrea Gabon Mozambique Nigeria South Sudan United Republic of Tanzania
OPTIMIZING HIV MANAGEMENT IN RESOURCE-LIMITED SETTINGS
Global State of Paediatric ART
UNAIDS report on the global AIDS epidemic 2013. Available at: http://www.unaids.org/en/media/unaids/contentassets/documents/epidemiology/2013/gr2013/UNAIDS_Global_Report_2013_en.pdf
Number of new HIV infections among children in low- and middle-income countries, 2001–2012 and 2015 target
2001 2009 2012 2015 0
100,000
200,000
300,000
400,000
500,000
600,000
700,000
New
HIV
infe
ctio
ns
-52% 2001–2012
-35% 2009–2012
40,000
-90%
OPTIMIZING HIV MANAGEMENT IN RESOURCE-LIMITED SETTINGS
Global State of Paediatric ART
UNAIDS report on the global AIDS epidemic 2013. Available at: http://www.unaids.org/en/media/unaids/contentassets/documents/epidemiology/2013/gr2013/UNAIDS_Global_Report_2013_en.pdf
Projected impact on new child HIV infections by programmes to prevent mother-to-child transmission,
21 Global Plan priority countries in sub-Saharan Africa, 2009–2015
2009 2012 2015 0
50,000
100,000
150,000
200,000
250,000
300,000
350,000
New
HIV
infe
ctio
ns
2012 coverage maintained ARV coverage scaled up to 90% Eliminate unmet need for family planning Reduce incidence by 50% Target
OPTIMIZING HIV MANAGEMENT IN RESOURCE-LIMITED SETTINGS
UNAIDS report on the global AIDS epidemic 2012. Available at: http://www.unaids.org/en/media/unaids/contentassets/documents/epidemiology/2012/gr2012/20121120_unaids_global_report_2012_with_annexes_en.pdf
28% COVERAGE FOR CHILDREN
HIV treatment coverage is 68% for women and 47% for
men in low- and middle-income countries, compared with 28%
for children worldwide
OPTIMIZING HIV MANAGEMENT IN RESOURCE-LIMITED SETTINGS
3.4 Kg Baby – First Referral to Hospital
9 months old
OPTIMIZING HIV MANAGEMENT IN RESOURCE-LIMITED SETTINGS
Key Barriers to Paediatric ART Initiation
Individual level factors:1
• Fear and stigma • Caregivers unawareness of HIV symptoms • Living without parents • Unemployment of the caregiver • Lack of perinatal prophylaxis • High transportation costs to the clinic
Health system issues: • Failure to link perinatal, well baby care to paediatric ART care • Problems with diagnosis of paediatric HIV (especially <18 months) • Healthcare worker
– Lack of identification of common HIV symptoms – Reluctance to start ART in children – perceived to be complicated
1. Boender TS, et al. AIDS Res Treat 2012;817506
OPTIMIZING HIV MANAGEMENT IN RESOURCE-LIMITED SETTINGS
Diagnosis
Optimal timing of HIV testing in children is a balancing act
Need for early testing
Sensitivity of test
OPTIMIZING HIV MANAGEMENT IN RESOURCE-LIMITED SETTINGS
Virologic Testing and Mortality Rates in Neonates
1. Dunn DT, et al. AIDS 1995;9:F7–11; 2. Bourne DE, et al. AIDS 2009;23:101–6
Birth 2–4 weeks 3–6 months Sensitivity 55% 90% 100%
Specificity 99.8% 100% 100%
Peak of mortality in South Africa & timing of virological testing & early treatment in different cohorts
Sensitivity and specificity of neonatal PCR
1 0 3 2 5 4 7 6 9 8 11 10 0
1000
2000
3000
4000
HIV-
rela
ted
deat
hs
Age at death (months) 6-week PCR
Results
ART
initi
atio
n un
der c
urre
nt
reco
mm
enda
tion
of 6
-wee
k PC
R te
st
OPTIMIZING HIV MANAGEMENT IN RESOURCE-LIMITED SETTINGS
Early Infant Diagnosis
WHO 20131 SA Guidelines2
DHHS Guidelines3 BHIVA4
Birth X (high risk) X (high risk) X
2–4 weeks X
4–6 weeks X X X X (2 weeks post prophylaxis)
12 weeks X (2 months post prophylaxis)
4–6 months X 2–4 weeks after stopping breastfeeding or cessation of ARV prophylaxis
X (POST BF
ONLY) X
Symptomatic infant X X X X
1. WHO. The use of antiretroviral drugs for treating and preventing HIV infection: recommendations for a public health approach. 2013 revision. Available at: http://apps.who.int/iris/bitstream/10665/85321/1/9789241505727_eng.pdf; 2. The South African Antiretroviral Treatment Guidelines 2013. Available at: http://www.sahivsoc.org/upload/documents/2013%20ART%20GuidelinesShort%20Combined%20FINAL%20draft%20guidelines%2014%20March%202013.pdf; 3. DHHS. Recommendations for use of antiretroviral drugs in pregnant HIV-1-infected women for maternal health and interventions to reduce perinatal HIV transmission in the United States. July 31, 2012. Available at: http://aidsinfo.nih.gov/contentfiles/lvguidelines/perinatalgl.pdf; 4. BHIVA guidelines for the management of HIV infection in pregnant women 2012. Available at: http://www.bhiva.org/documents/Guidelines/Pregnancy/2012/hiv1030_6.pdf
OPTIMIZING HIV MANAGEMENT IN RESOURCE-LIMITED SETTINGS
Point-of Care EID Tests
WHO supplement to the 2013 consolidated guidelines. Available at: http://apps.who.int/iris/bitstream/10665/104264/1/9789241506830_eng.pdf?ua=1
2013 2014 2015 2016
LiatTM Analyser IQuum
Alere Q Alere
EOSCAPE HIVTM Rapid RNA Assay System Wave 80 Biosciences
LYNX Viral Load Platform NWGHF
RT CPA HIV-1 Viral Load
Ustar
Gene-RADAR® Nanobiosym
Viral Load Assay with BART
Lumora
Micronics
All
BioHelix
Cavidi AMP Gene Xpert® System Cepheid
Samba VL DDU/Cambridge
LYNX HIV p24 Antigen NWGHF
TruelabTM PCR Molbio/bigTec
SAMBA EID DDU/Cambridge
OPTIMIZING HIV MANAGEMENT IN RESOURCE-LIMITED SETTINGS
When To Start ART Age WHO 20131 SA guidelines2 DHHS (USA)3 BHIVA4
<1 year Start all Start all Start all Start all 1–3 years Start all
Start all CDC B/C or
VL >100 000 c/mL or CD4 <1000 cells/μl/25%
CDC B/C or CD4 <1000
cells/μl/25%*
3–5 years Start all Start all CDC B/C or VL >100 000 c/mL
or CD4 <750 cells/μl/25%
CDC B/C or VL >100 000 c/mL
or CD4 <500 cells/μl/20%*
>5 years WHO Stage 3/4 or CD4 <500 cells/μl
(prioritize <350 cells/μl)
WHO Stage 3/4 or CD4 <350 cells/μl
CDC B/C or VL >100 000 c/mL
or CD4 <350 or 500 cells/μl
CDC B/C or CD4 <350 or
500 cells/μl
*consider VL >100 000 c/mL 1. WHO. The use of antiretroviral drugs for treating and preventing HIV infection: recommendations for a public health approach. 2013 revision. Available at: http://apps.who.int/iris/bitstream/10665/85321/1/9789241505727_eng.pdf; 2. The South African Antiretroviral Treatment Guidelines 2013. Available at: http://www.sahivsoc.org/upload/documents/2013%20ART%20GuidelinesShort%20Combined%20FINAL%20draft%20guidelines%2014%20March%202013.pdf; 3. DHHS. Recommendations for use of antiretroviral drugs in pregnant HIV-1-infected women for maternal health and interventions to reduce perinatal HIV transmission in the United States. July 31, 2012. Available at: http://aidsinfo.nih.gov/contentfiles/lvguidelines/perinatalgl.pdf; 4. BHIVA guidelines for the management of HIV infection in pregnant women 2012. Available at: http://www.bhiva.org/documents/Guidelines/Pregnancy/2012/hiv1030_6.pdf
OPTIMIZING HIV MANAGEMENT IN RESOURCE-LIMITED SETTINGS
Violari A, et al. IAS 2007 abstract WESS103
ART initiated before 12 weeks reduces early mortality in
young HIV-infected infants: evidence from the Children with HIV Early
Antiretroviral Therapy (CHER) Study
Avy Violari, Mark Cotton, Di Gibb, Abdel Babiker, Jan Steyn, Patrick Jean-Philippe, James McIntyre
PHRU, University of Witwatersrand; KID-CRU, Stellenbosch University; MRC-CTU UK; DAIDS NIAID, NIH
OPTIMIZING HIV MANAGEMENT IN RESOURCE-LIMITED SETTINGS
Mortality Rates
Violari A, et al. IAS 2007 abstract WESS103
Variable Early Treatment
(arm 2/3) n=252
Deferred Treatment (arm 1) n=125
Total n=377
Died (%) 10 (4%) 20 (16%) 30 (8%)
Person Years of follow-up 167 79 246
Rate per 100 PY (95% CI) 6.0 (2.9; 10) 25.3 (15.5; 39.0) 12.2 (8.2; 17.4)
Hazard Ratio 0.24 (0.11; 0.51)
P-value 0.0002
OPTIMIZING HIV MANAGEMENT IN RESOURCE-LIMITED SETTINGS
When To Start ART in Children Aged 2–5 Years: A Collaborative Causal Modelling Analysis of Cohort Studies from Southern Africa
Schomaker M, et al. Plos Medicine 2013;10:e1001555
0.00
0.01
0.02
0.03
0.04
Mor
talit
y
Follow-up time (months) 0 3 9 12 18 27 30 1 6 15 21 24 33 36
Intervention* 750,25% Always ART
Estimated cumulative mortality for immediate vs. deferred ART
*Estimated cumulative mortality (including 95% bootstrap CI, dashed lines) over 3 y if ART was given irrespective of CD4 count and CD4% (‘always ART’) and if ART was given if the CD4 count was below 750 cells/mm3 or the CD4% was below 25% (‘750,25%’)
Estimated probability of falling below a CD4+ count of 750 cells/mm3 or a CD4+ of 25%
0
25
50
75
Follow-up time (years) 0 1 2 3
100
Thre
shol
d re
ache
d (%
)
OPTIMIZING HIV MANAGEMENT IN RESOURCE-LIMITED SETTINGS
What To Start
WHO. The use of antiretroviral drugs for treating and preventing HIV infection: recommendations for a public health approach. 2013 revision. Available at: http://apps.who.int/iris/bitstream/10665/85321/1/9789241505727_eng.pdf
Summary of first-line ART regimens for children younger than three years
Preferred regimens ABC or AZT + 3TC + LPV/r
Alternative regimens ABC or AZT + 3TC + NVP
Special circumstances d4T + 3TC + LPV/r d4T + 3TC + NVP
OPTIMIZING HIV MANAGEMENT IN RESOURCE-LIMITED SETTINGS
Nevirapine vs. Ritonavir-boosted Lopinavir for HIV-infected Children
Violari A, et al. N Engl J Med 2012;366:2380–9
0
10
20
30
40
50
60
70
80
90
100
On
trea
tmen
t with
no
viro
logi
c fa
ilure
(%)
Week 0 24 48 72 96 120 144 168
Lopinavir/r
Nevirapine
Failure rate at 24 weeks Nevirapine, 41.5% Lopinavir/r, 19.4%
Time to virologic failure or treatment discontinuation, age <12 months
No. at risk Nevirapine 41 28 15 10 5 3 2 2 Lopinavir/r 36 33 25 13 7 6 5 3
Time to virologic failure or treatment discontinuation, age ≥12 months
No. at risk Nevirapine 106 81 53 37 20 17 10 5 Lopinavir/r 104 92 68 41 26 20 12 6
0
10
20
30
40
50
60
70
80
90
100
On
trea
tmen
t with
no
viro
logi
c fa
ilure
(%)
Week 0 24 48 72 96 120 144 168
Lopinavir/r
Nevirapine Failure rate at 24 weeks Nevirapine, 40.6% Lopinavir/r, 19.2%
OPTIMIZING HIV MANAGEMENT IN RESOURCE-LIMITED SETTINGS
WHO 2013: Summary of Recommended ART Regimens for Children who need TB Treatment
Recommended regimens for children and adolescents initiating ART while on TB treatment
Younger than 3 years Two NRTIs + NVP, ensuring that dose is 200 mg/m2
or Triple NRTI (AZT + 3TC + ABC)
3 years and older Two NRTIs + EFV or Triple NRTI (AZT + 3TC + ABC)
Recommended regimen for children and infants initiating TB treatment while receiving ART
Child on standard NNRTI-based regimen (two NRTIs + EFV or NVP)
Younger than 3 years
Continue NVP, ensuring that dose is 200 mg/m2
or Triple NRTI (AZT + 3TC + ABC)
3 years and older
If the child is receiving EFV, continue the same regimen If the child is receiving NVP, substitute with EFV or Triple NRTI (AZT + 3TC + ABC)
WHO. The use of antiretroviral drugs for treating and preventing HIV infection: recommendations for a public health approach. 2013 revision. Available at: http://apps.who.int/iris/bitstream/10665/85321/1/9789241505727_eng.pdf
OPTIMIZING HIV MANAGEMENT IN RESOURCE-LIMITED SETTINGS
WHO 2013: Summary of Recommended ART Regimens for Children who need TB Treatment
WHO. The use of antiretroviral drugs for treating and preventing HIV infection: recommendations for a public health approach. 2013 revision. Available at: http://apps.who.int/iris/bitstream/10665/85321/1/9789241505727_eng.pdf
Recommended regimen for children and infants initiating TB treatment while receiving ART
Child on standard PI-based regimen (two NRTIs + LPV/r)
Younger than 3 years
Triple NRTI (AZT + 3TC + ABC) or Substitute NVP for LPV/r, ensuring that dose is 200 mg/m2
or Continue LPV/r; consider adding RTV to achieve the full therapeutic dose
3 years and older
If the child has no history of failure of an NNRTI-based regimen: Substitute with EFV or Triple NRTI (AZT + 3TC + ABC) or Continue LPV/r; consider adding RTV to achieve the full therapeutic dose If the child has a history of failure of an NNRTI-based regimen: Triple NRTI (AZT + 3TC + ABC) or Continue LPV/r consider adding RTV to achieve the full therapeutic dose Consider consultation with experts for constructing a second-line regimen
OPTIMIZING HIV MANAGEMENT IN RESOURCE-LIMITED SETTINGS
Children 3 years to less than 10 years and adolescents <35 kg
Adolescents (10 to 19 years) ≥35 kg
Preferred ABC + 3TC + EFV TDF + 3TC (or FTC) + EFV
Alternatives
ABC + 3TC + NVP AZT + 3TC + EFV AZT + 3TC + NVP TDF + 3TC (or FTC) + EFV TDF + 3TC (or FTC) + NVP
AZT + 3TC + EFV AZT + 3TC + NVP TDF + 3TC (or FTC) + NVP
Special circumstances d4T + 3TC + EFV d4T + 3TC + NVP
ABC + 3TC + EFV ABC + 3TC + NVP
WHO 2013: Summary of Recommended First-line ART Regimens for Children and Adolescents
WHO. The use of antiretroviral drugs for treating and preventing HIV infection: recommendations for a public health approach. 2013 revision. Available at: http://apps.who.int/iris/bitstream/10665/85321/1/9789241505727_eng.pdf
OPTIMIZING HIV MANAGEMENT IN RESOURCE-LIMITED SETTINGS
Algorithm for the WHO 2013 Recommendations for Children
WHO. The use of antiretroviral drugs for treating and preventing HIV infection: recommendations for a public health approach. 2013 revision. Available at: http://apps.who.int/iris/bitstream/10665/85321/1/9789241505727_eng.pdf
Infants and children infected with HIV
<5 years of age ≥5 years of age
WHO clinical stage 3 or 4 or
CD4+ ≤500 cells/mm3?
Initiate ART Monitor clinical stage and CD4 Initiate ART
<3 years of age?
Initiate one of the following regimens:
Preferred option: TDF + 3TC (or FTC) + EFV
Alternative options: AZT + 3TC + EFV AZT + 3TC + NVP TDF + 3TC (or FTC) + NVP
Initiate one of the following regimens:
Preferred option: ABC + 3TC + EFV
Alternative options: ABC + 3TC + NVP AZT + 3TC + EFV AZT + 3TC + NVP TDF + 3TC (or FTC) + EFV TDF + 3TC (or FTC) + NVP
Initiate one of the following regimens:
Preferred option: ABC or AZT + 3TC + LPV/r
Alternative options: ABC or AZT + 3TC + NVP
Wha
t firs
t-lin
e AR
T to
star
t in
chi
ldre
n
<10 years of age or weight <35 kg
Yes No
No Yes No
Whe
n to
star
t ART
in
chi
ldre
n
Yes
OPTIMIZING HIV MANAGEMENT IN RESOURCE-LIMITED SETTINGS
HIV Testing and Counselling of Adolescents
HIV testing and counselling, with linkages to prevention, treatment and care, is recommended for adolescents from key populations in all settings (generalized, low and concentrated epidemics) (strong recommendation, very-low-quality evidence)
HIV testing and counselling with linkage to prevention, treatment and care is recommended for all adolescents in generalized epidemics (strong recommendation, very-low-quality evidence)
We suggest that HIV testing and counselling with linkage to prevention, treatment and care be accessible to all adolescents in low and concentrated epidemics (conditional recommendation, very-low-quality evidence)
We suggest that adolescents be counselled about the potential benefits and risks of disclosure of their HIV status and empowered and supported to determine if, when, how and to whom to disclose (conditional recommendation, very-low quality evidence)
WHO. The use of antiretroviral drugs for treating and preventing HIV infection: recommendations for a public health approach. 2013 revision. Available at: http://apps.who.int/iris/bitstream/10665/85321/1/9789241505727_eng.pdf
OPTIMIZING HIV MANAGEMENT IN RESOURCE-LIMITED SETTINGS
Laboratory Monitoring Before and After Initiating ART Phase of HIV management
Recommended Desirable (if feasible)
HIV diagnosis
HIV serology, CD4 cell count TB screening
HBV (HBsAg) serology
HCV serology Cryptococcus antigen if CD4 count ≤100 cells/mm3
Screening for sexually transmitted infections Assessment for major noncommunicable chronic diseases and comorbidities
Follow-up before ART
CD4 cell count (every 6–12 months)
ART initiation
CD4 cell count Haemoglobin test for AZT
Pregnancy test Blood pressure measurement Urine dipsticks for glycosuria and estimated glomerular filtration rate (eGFR) and serum creatinine for TDF
Alanine aminotransferase for NVP
Receiving ART CD4 cell count (every 6 months) HIV viral load (at 6 months after initiating ART and every 12 months thereafter)
Urine dipstick for glycosuria and serum creatinine for TDF
Treatment failure CD4 cell count HIV viral load
HBV (HBsAg) serology (before switching ART regimen if this testing was not done or if the result was negative at baseline)
WHO. The use of antiretroviral drugs for treating and preventing HIV infection: recommendations for a public health approach. 2013 revision. Available at: http://apps.who.int/iris/bitstream/10665/85321/1/9789241505727_eng.pdf
OPTIMIZING HIV MANAGEMENT IN RESOURCE-LIMITED SETTINGS
When To Switch?
All populations
Viral load is recommended as the preferred monitoring approach to diagnose and confirm ARV treatment failure (strong recommendation, low-quality evidence)
If viral load is not routinely available, CD4 count and clinical monitoring should be used to diagnose treatment failure (strong recommendation, moderate-quality evidence)
WHO. The use of antiretroviral drugs for treating and preventing HIV infection: recommendations for a public health approach. 2013 revision. Available at: http://apps.who.int/iris/bitstream/10665/85321/1/9789241505727_eng.pdf
OPTIMIZING HIV MANAGEMENT IN RESOURCE-LIMITED SETTINGS
Treatment Failure Pathway
Detectable Viral Load:
≠ Change of regimen
= Call to action – Intensified adherence
1. Early recognition of
virological failure
2. Early initiation of enhanced adherence
3. Appropriate referral for
resistance testing
OPTIMIZING HIV MANAGEMENT IN RESOURCE-LIMITED SETTINGS
Advanced Clinical Care – 23/04/2014
OPTIMIZING HIV MANAGEMENT IN RESOURCE-LIMITED SETTINGS
WHO Definitions of Clinical, Immunological and Virological Failure for the Decision to Switch ART Regimens
WHO. The use of antiretroviral drugs for treating and preventing HIV infection: recommendations for a public health approach. 2013 revision. Available at: http://apps.who.int/iris/bitstream/10665/85321/1/9789241505727_eng.pdf
Failure Definition Comments
Clinical failure
Adults and adolescents New or recurrent clinical event indicating severe immunodeficiency (WHO clinical stage 4 condition) after 6 months of effective treatment Children New or recurrent clinical event indicating advanced or severe immunodefiency (WHO clinical stage 3 and 4 clinical condition with exception of TB) after 6 months of effective treatment
The condition must be differentiated from immune reconstitution inflammatory syndrome occurring after initiating ART For adults, certain WHO clinical stage 3 conditions (pulmonary TB and severe bacterial infections) may also indicate treatment failure
Immunological failure
Adults and adolescents CD4 count falls to the baseline (or below) or Persistent CD4 levels below 100 cells/mm3
Without concomitant or recent infection to cause a transient decline in the CD4 cell count A systematic review found that current WHO clinical and immunological criteria have low sensitivity and positive predictive value for identifying individuals with virological failure. The predicted value would be expected to be even lower with earlier ART initiation and treatment failure at higher CD4 cell counts. There is currently no proposed alternative definition of treatment failure and no validated alternative definition of immunological failure
Children Younger than 5 years: Persistent CD4 levels below 200 cells/mm3 or <10% Older than 5 years: Persistent CD4 levels below 100 cells/mm3
Virological failure
Plasma viral load above 1000 copies/mL based on two consecutive viral load measurements after 3 months, with adherence support
The optimal threshold for defining virological failure and the need for switching ART regimen has not been determined An individual must be taking ART for at least 6 months before it can be determined that a regimen has failed Assessment of viral load using DBS and point-of-care technologies should use a higher threshold
OPTIMIZING HIV MANAGEMENT IN RESOURCE-LIMITED SETTINGS
Simplified Dosing of Child-friendly Fixed-dose Solid Formulations for Twice-daily Dosing among Children
WHO. The use of antiretroviral drugs for treating and preventing HIV infection: recommendations for a public health approach. 2013 revision. Available at: http://apps.who.int/iris/bitstream/10665/85321/1/9789241505727_eng.pdf
Drug Strength of tablets (mg)
Number of tablets by weight band morning and evening Strength of
adult tablets (mg)
Number of tablets by
weight band 3–5.9 kg 6–9.9 kg 10–13.9 kg 14–19.9 kg 20–24.9 kg 25–34.9 kg AM PM AM PM AM PM AM PM AM PM AM PM
AZT/3TC
Tablet (dispersible) 60 mg/30 mg 1 1 1.5 1.5 2 2 2.5 2.5 3 3 300/150 1 1
AZT/3TC/NVP
Tablet (dispersible) 60 mg/30 mg/50 mg 1 1 1.5 1.5 2 2 2.5 2.5 3 3 300/150/200 1 1
ABC/AZT/3TC
Tablet (dispersible) 60 mg/60 mg/30 mg 1 1 1.5 1.5 2 2 2.5 2.5 3 3 300/300/150 1 1
ABC/3TC
Tablet (dispersible) 60 mg/30 mg 1 1 1.5 1.5 2 2 2.5 2.5 3 3 600/300 0.5 0.5
d4T/3TC
Tablet (dispersible) 6 mg/30 mg 1 1 1.5 1.5 2 2 2.5 2.5 3 3 30/150 1 1
d4T/3TC/NVP
Tablet (dispersible) 6 mg/30 mg/50 mg 1 1 1.5 1.5 2 2 2.5 2.5 3 3 - 4 4
OPTIMIZING HIV MANAGEMENT IN RESOURCE-LIMITED SETTINGS
Simplified Dosing of Child-friendly Solid Formulations for Once-daily Dosing in Children
WHO. The use of antiretroviral drugs for treating and preventing HIV infection: recommendations for a public health approach. 2013 revision. Available at: http://apps.who.int/iris/bitstream/10665/85321/1/9789241505727_eng.pdf
Drug Strength of tablets (mg)
Number of tablets or capsules by weight band once daily Strength of
tablet (mg)
Number of tablets by
weight band
3–5.9 kg 6–9.9 kg 10–13.9 kg 14–19.9 kg 20–24.9 kg 25–34.9 kg
EFV
Tablet (scored) 200 mg - - 1 1.5 1.5 200 2
Tablet (double scored)
600 mg - - one third one half two thirds 600 2/3
ABC/3TC
Tablet (dispersible) 60/30 mg 2 3 4 5 6 600 + 300 1
OPTIMIZING HIV MANAGEMENT IN RESOURCE-LIMITED SETTINGS
Simplified Dosing of Child-friendly Solid and Liquid Formulations for Twice-daily Dosing
WHO. The use of antiretroviral drugs for treating and preventing HIV infection: recommendations for a public health approach. 2013 revision. Available at: http://apps.who.int/iris/bitstream/10665/85321/1/9789241505727_eng.pdf
Drug Strength of tablets (mg)
Number of tablets by weight band morning and evening Strength of adult tablets
(mg)
Number of tablets by
weight band 3–5.9 kg 6–9.9 kg 10–13.9 kg 14–19.9 kg 20–24.9 kg 25–34.9 kg
AM PM AM PM AM PM AM PM AM PM AM PM Solid formulations
3TC Table (dispersible) 30 mg 1 1 1.5 1.5 2 2 2.5 2.5 3 3 150 1 1 AZT Table (dispersible) 60 mg 1 1 1.5 1.5 2 2 2.5 2.5 3 3 300 1 1 ABC Table (dispersible) 60 mg 1 1 1.5 1.5 2 2 2.5 2.5 3 3 300 1 1 NVP Table (dispersible) 30 mg 1 1 1.5 1.5 2 2 2.5 2.5 3 3 200 1 1
LPV/r Tablet (heat stable) 100 mg/25 mg - - - - 2 1 2 2 2 2 100/25 3 3
Liquid formulations AZT 10 mg/mL 6 mL 6 mL 9 mL 9 mL 12 mL 12 mL - - - - - - - ABC 20 mg/mL 3 mL 3 mL 4 mL 4 mL 6 mL 6 mL - - - - - - - 3TC 10 mg/mL 3 mL 3 mL 4 mL 4 mL 6 mL 6 mL - - - - - - - NVP 10 mg/mL 5 mL 5 mL 8 mL 8 mL 10 mL 10 mL - - - - - - -
LPV/r 80/20 mg/mL 1 mL 1 mL 1.5 mL 1.5 mL 2 mL 2 mL 2.5 mL
2.5 mL 3 mL 3 mL - - -
OPTIMIZING HIV MANAGEMENT IN RESOURCE-LIMITED SETTINGS
Drug Strength of tablet or sprinkle sachet
or capsule (mg)
No. of tables or sprinkle capsules/sachets by weight band 3–5.9 kg 6–9.9 kg 10–13.9 kg 14–19.9 kg 20–24.9 kg 25–34.9 kg
AM PM AM PM AM PM AM PM AM PM AM PM ABC/3TC/NVP 60 mg/30 mg/50 mg 1 1 1.5 1.5 2 2 2.5 2.5 3 3 4 4 LPV/r sprinkles 40 mg/10 mg 2 2 3 3 4 4 5 5 6 6 -
ABC/3TC/LPV/r 30 mg/15 mg/40 mg/ 10 mg 2 2 3 3 4 4 5 5 6 6 -
AZT/3TC/LPV/r 30 mg/15 mg/40 mg/ 10 mg 2 2 3 3 4 4 5 5 6 6 -
DRV/r 240 mg/40 mg - - - - 1 1 1 1 2 1 - ARV/r 100 mg/33 mg - - 1 1 2 - ABC/3TC 120 mg/60 mg 1 1.5 2 2.5 3 - TDF/3TC 75 mg/75 mg - - 1.5 2 2.5 3–3.5 TDF/3TC/EFV 75 mg/75 mg/150 mg - - 1.5 2 2.5 3–3.5 TDF/3TC adult double scored
300 mg/300 mg - - one third one half two thirds 1
TDF/3TC/EFV adult double scored
300 mg/300 mg/ 600 mg - - one third one half two thirds 1
Simplified Dosing for Urgently Needed ARV Drugs for Children Recommended by The Paediatric Antiretroviral Working Group
WHO. The use of antiretroviral drugs for treating and preventing HIV infection: recommendations for a public health approach. 2013 revision. Available at: http://apps.who.int/iris/bitstream/10665/85321/1/9789241505727_eng.pdf
OPTIMIZING HIV MANAGEMENT IN RESOURCE-LIMITED SETTINGS
What To Switch To?
WHO. The use of antiretroviral drugs for treating and preventing HIV infection: recommendations for a public health approach. 2013 revision. Available at: http://apps.who.int/iris/bitstream/10665/85321/1/9789241505727_eng.pdf
Second-line ART Preferred regimens Alternative regimens Adults and adolescents (≥10 years), including pregnant and breastfeeding women
AZT + 3TC + LPV/ra
AZT + 3TC + ATV/ra TDF + 3TC (or FTC) + ATV/r TDF + 3TC (or FTC) + LPV/r
Children
If a NNRTI-based first- line regimen was used ABC + 3TC + LPV/rb ABC + 3TC + LPV/rb
TDF + 3TC (or FTC) + LPV/rb
If a PI-based first-line regimen was used
<3 years No change from first-line regimen in usec AZT (or ABC) + 3TC + NVP
3 years to less than 10 years
AZT (or ABC) + 3TC + EFV ABC (or TDF) + 3TC + NVP
aDRV/r can be used as an alternative PI and SQV/r in special situations; neither is currently available as a heat-stable fixed-dose combination, but a DRV + RTV heat-stable fixed-dose combination is currently in development. bATV/r can be used as an alternative to LPV/r for children older than six years. cUnless failure is caused by lack of adherence resulting from poor palatability of LPV/r.
Summary of preferred second-line ART regimens for adults, adolescents, pregnant women and children
OPTIMIZING HIV MANAGEMENT IN RESOURCE-LIMITED SETTINGS
Maintaining Good Adherence in Children
Challenging:
• Young child: – Appropriate formulation for the age of the child – Fitting the ART regimen into the child’s schedule – ART fatigue
• Adolescent and pre-adolescent: – Disclosure – Challenging of authority / Development of an individual
personality – Ease of taking chronic medication
OPTIMIZING HIV MANAGEMENT IN RESOURCE-LIMITED SETTINGS
New Drugs/New Recommendations of Established Drugs
Abacavir • Once daily dosing
Efavirenz • FDA approved in children >3/12 and >3.5 kg
Nevirapine • XR or extended release in those >6 years
Darunavir • Once daily dosing only in those >12 years • Although FDA approved in those <12 years, not enough data for
once daily dosing Raltegravir • FDA approved for infants and children >4 weeks >3 kg • Sachets for reconstitution
OPTIMIZING HIV MANAGEMENT IN RESOURCE-LIMITED SETTINGS
New Formulations for Children
Partnership between CIPLA and DNDi Specially created for children <3 years of age By 2015 2 new FDCs plus new ritonavir Ritonavir • For babies with TB and HIV • Granules
FDCs • 4-in-1 (LPV/r/AZT/3TC and LPV/r/ABC/3TC) • Granules • Sprinkled over food/mixed with milk • Palatable (masked taste) • No refrigeration