Long Term Complications of Treatment in Children By By Kulkanya Chokephaibukit, MD Kulkanya Chokephaibukit, MD Professor of Pediatrics Professor of Pediatrics Faculty of Medicine Siriraj Hospital Faculty of Medicine Siriraj Hospital Mahidol University, Bangkok, Mahidol University, Bangkok, Thailand Thailand Lecture at HIVNAT 25 July 2013
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Long Term Complications of Treatment in Children By Kulkanya Chokephaibukit, MD Professor of Pediatrics Faculty of Medicine Siriraj Hospital Mahidol University,
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Long Term Complications of
Treatment in Children
By By
Kulkanya Chokephaibukit, MDKulkanya Chokephaibukit, MDProfessor of PediatricsProfessor of Pediatrics
Faculty of Medicine Siriraj HospitalFaculty of Medicine Siriraj Hospital
Lecture at HIVNAT 25 July 2013Lecture at HIVNAT 25 July 2013
HIV is an acceptable virus to live with!
Emily, 7 year-old girl with ALL cured by
using HIV gene therapy
A disabled form of HIV deliver the gene to make chimeric
antigen receptor T-cell (CTL019)of the patient that recognize the and destroy
cancer cells
Concerning Long Term Complications of Treatment
in HIV-Infected Children and Adolescents
• Lipodystrophy, esp. facial lipoatrophy
• Metabolic complications that may result in
cardiovascular diseases/coronary heart
diseases/stroke, DM
• Kidney dysfunction
• Fractures risk/osteopenia/vitamin D deficiency
• Neuro/psychiatric problems
A 9 year-old boy with perinatal HIV
Chief Complaint: Hyperpigmentation of neck and armpit
for 2 years
History:
• Maternal HIV without perinatal treatment
• Diagnosis of HIV infection by serology at 18 month-old , CD4: 256 cell/mm3 (12.39%)
• He was started on AZT+3TC (in 1998), then changed to HAART
• At 7 year-old, started to gain weight, very good appetite, and noticed hyperpigmentation
Familial Hx: Mom died from AIDS. Live with grandparents,
both had DM
Age %CD4 CD4 count VL ART
18 mo 12.39 256 - AZT+3TC
3 Y 2.03 48 - d4T+ddI+EFV
4.5 Y 2.79 72 504,000M41L, D67N
K101E, V179D
d4T+3TC+EFV
5.5 Y - - - AZT+3TC+IDV/r
5.6 Y 3.04 137 <40 AZT+3TC+IDV/r
The 9 year-old boy with dark neck for 2 years
Date %CD4 CD4
count
VL ART
5.6 Y 3.04 137 <40 AZT+3TC+IDV/r
8.5 Y 19.63 930 - AZT+3TC+IDV/r
9Y 19.35 592 - AZT+3TC+LPV/r
9.5 Y 23.86 679 <40 AZT+3TC+LPV/r
The 9 year-old boy with dark neck for 2 years
Physical Examination:
• Wt 46.9 kg (>P97), Ht 140.8 cm (P97), 146% Ideal BW, BMI
23.9 kg/m2, WC 76.5 cm, HC 73.7 cm
W/H ratio 1.04
• GA: loss of pad of fat/ lower limbs, dorsocervical hump
• Chest: gynecomastia
• GU: testes 5 cc, PH Tanner II
• Normal findings for heart, lungs, abdomen, and neuro
examinations
The 9 year-old boy with dark neck
Hyperpigmentation of the neck and
armpits, dorsocervical hump
What is your diagnosis of his skin hyperpigmentation?
A. genetic B. Acanthosis nigricansC. poor hygeine
What is the common condition associated with this skin hyperpigmentation?
A. Insulin resistance and diabetes
B. Dyslipidemia
C. Malignant melanoma
Acanthosis nigricansAcanthosis nigricansA clue for IRA clue for IR
• Hyperpigmented velvety macules and patches and progress to palpable plaques. Mostly observed at the intertriginous areas of the axilla, groin, and posterior neck
• Causes:
- Obesity, particularly with darker skin
color. Children BMI>98th tile have AN in 62%.1
- Diabetes and Insulin resistance.2
- Polycystic ovarian syndrome
- Malignancy: adenocarcinomas of the GI tract (70-90%), and others
1.Krawczyk M. Pol Arch Med Wewn. Mar 2009;119(3):180-3. 2. Sadeghian G. J Dermatol. Apr 2009;36(4):209-12
Problem ListsProblem Lists
• Obesity
• Acanthosis nigricans
• Lipodystrophy (mild facial lipoatrophy)
• FBS = 159mg/dl (Provisional DM)
• Metabolic syndrome?
Lipodystrophy in HIV-infected children
Incidence vary 10-50%1-4 due to lack of consensus for definition
Associated with PI and stavudine PI: Predominate with truncal obesity, buffalo
hump, and less periheral lipoatrophy d4T: Predominate with facial, associated with
HLA-B*40015 and Fas gene6
Likely to appear in early adolescence1,7
1.Lapphra K. J Med Assoc Thai. 2005. 2. Taylor P. Pediatrics 2004 3. Amaya RA. Pediatr Infect Dis J. 2002. 4. Sawawiboon N. Int J STD AIDS 2012, 5. Wangsomboonsiri W. CID 2010;50(4):597-604, 6. Likan
onsakul S, AIDS Res Hum Retroviruses. 2012 Jul 9., 7. Alam NM. J Acquir Immune Defic Syndr. 2012; 59(3): 314–324
Characteristics of Lipodystrophy from Protease Inhibitors
• Fat gain on abdomen, breast, and dorsocervical hump
• Fat loss from peripheral extremities• Fat gain in visceral organs
Facial and peripheral lipoatrophy following >6 months of stavudine treatment, found in 38% of d4T Rx, occur around early adolescence Sawawiboon N. International Journal of STD & AIDS 2012; 23: 497–501
Lipodystrophy from d4T
Alam NM. J Acquir Immune Defic Syndr. 2012 March 1; 59(3): 314–324
Body fat abnormality in HIV-infected children and adolescents: The difference of regions
Lipoatrophy 23%
Europe (N= 426, LD = 42% Receiving PI 60%, Received d4T 10%
Thailand, N=202, LD = 25%Receiving PI 41%, Received d4T 60%
Lipohypertrophy or combine 2.5%
%
No fat maldistribution 75%
Sawawiboon N. International Journal of STD & AIDS 2012; 23: 497–501
Study Population
Facial Lipoatrophy may improve after stopping d4T
Improvement found in 23%, at mean duration of 45 months after stopping d4T, around early adolescence
Sawawiboon N. International Journal of STD & AIDS 2012; 23: 497–501
Facial lipoatrophyIs it reversible?
Need to stop d4T before reaching
adolescence
What about high FBS once?
What would you do?
A. Control sugar intake and repeat FBS
B. Perform OGTT
C. It’s mostly transient, repeat FBS
in 6 months
Interpretation of Fasting Blood Sugar
Provisional DMNormal FBS
Impaired FBS
100 mg/dl 126 mg/dlFBS
Oral Glucose Challenge Test: Must be done in all cases of impair FBS
Provisional DMNormal OGTT
Impaired OGTT
140 mg/dl 200 mg/dl2 hr PG
Why do we need to worry about DM?
A. A lot of treatment and complication of DM to follow, interrupt normal life
B. DM increased risk of ART associated CVD
C. Early intervention (exercise and metformin) may prevent or delayed DM and complications
Symptoms of DM plus casual BG ≥200 mg/dL (polyuria, polydipsia, and unexplained weight
loss) or FBS ≥126 mg/dL or 2-hr BS ≥200 mg/dL during an OGTT or HbA1C ≥ 6.5%
Diagnosis of Diabetes MellitusDiagnosis of Diabetes Mellitus
Oral Glucose Tolerance Test
0 30 60 90 120
BS 58 134 181 165 188
Insulin 88.7 842.3 >1000 >1000 >1000
Normal fasting lipid profile
Chol LDL-C HDL-C TG
174 120 51 140
Diagnosis: Impaired OGTT with hyperinsulinemia>>Pre-diabetes
9 yo. boy with acanthosis nigricans9 yo. boy with acanthosis nigricans
Prevalence in adults 10-20%
Increase prevalence in patients receiving HAART with lipodystrophy1
Incidence in children is much lower However, 19% of children receiving PI had
impair OGTT2
Insulin Resistance and Type 2 Diabetes in HIV-Infected Children
1.Vigouroux C. Diabetes & Metabolism 19992. Bitnun A. J Clin Endocrinol Metab 2005
Classical T2DM risk
factors
Obesity (abdominal)
Physical inactivity
Genetic
Family history
Race Older age
Dyslipidemia
HIV-associated risk factors
Peripheral lipoatrophy
Increased liver or muscle fat
Inflammatory cytokines
Low testosterone
Oxidant stress
HCV infection
PIs therapy
Insulin Resistance and HIV
How can we prevent DM in this patient?
A. Diet and exercise
B. Diet and exercise and metformin
C. Control other factor:
dyslipidemia
Reduction in the Incidence of T2 DM with Lifestyle Intervention or Metformin
• 3234 patients with IFG or IGT
• Treatment; placebo, metformin, lifestyle-modification program
• Lifestyle-modification program: 7% weight loss and 150 mins of physical activity per week
• Average follow-up was 2.8 yr
Diabetes Prevention Program. N Engl J Med 2002:346:393-403
Exercise and Metformin can prevent DM
Diabetes Prevention Program. N Engl J Med 2002:346:393-403
At 3 years
28.9%
21.7%
14.4%
Lifestyle gr.: reduced the risk of converting to DM by 58%Metformin gr.: reduced the risk of converting to DM by 31%
Incidence of DM in lifestyle gr.: 39% lower than metformin gr.
Exercise and Metformin can prevent DM
None is approved in children
Troglitazone (TRIPOD) (withdrawn due to rare hepatitis)
Hispanic women with GDM 56% risk reduction
Buchanan TA et al. Diabetes 2002
Acarbose (STOPP-NIDDM)
Subject with IGT 32% decreased conversion to T2DM
Chiasson JL et al. JAMA 2003
Xenical (XENDOS)
Subject with BMI >29, lifestyle plus xenical vs placebo
37% risk reduction
Torgerson JS et al. Diabetes care 2004
Drugs that may delay or prevent the development of Type2 DM
A 9 Year-Old Boy with Perinatal HIV and Insulin-Resistance
Treatment: Metformin (500) 1 tab oral bid
Encourage healthy life style, exercise
Continue ART: AZT/3TC/LPV/r
Outcomes: 4 mo after treatment
Wt 44.4 kg (-2 kg),
Ht 142 cm, BMI 22 kg/m2 (-1.9)
WC 76.2 cm (-0.3 cm)
OGTT 12/1/07
0 30 60 90 120
BS 58 95 116 99 99
Insulin 13.19 130.9 249.4 139.3 161.1
0 30 60 90 120
BS 58 134 181 165 188
Insulin 88.7 842.3 >1000 >1000 >1000
OGTT 8/11/06
After 4 months of Metformin Rx and exercise: Improved hyperinsulinemia and BS
Fasting lipid profileDate Chol LDL-C HDL-C TG
7/25/06 174 120 51 140
12/7/07 232 138.4 71 113
6 Months later…He developed hyperlipidemia
NCEP Definition for Dyslipidemia in Children and Adults
TG was not established by NCEP; a TG level of 125 mg/dL approximates the mean 95th percentile for TGs in boys and girls during childhood and adolescence.
Why do we need to care about dyslipidemia? Should we just leave it for the adult doctors to take care of the business when the child grown-up!
It is an important risk factor for CVD in adults Atherosclerosis starts in childhood, esp. if TC>200 and
LDL-C >130 mg/dl Very common, found 60%-80% in children receiving HAART,
particularly PI1-3, found more in patients with lipodystrophy Some PI cause less dyslipidemia: ATV, DRV
1.Lapphra K. J Med Assoc Thai. 2005. 2. Taylor P. Pediatrics 2004. 3. Amaya RA. Pediatr Infect Dis J. 2002
Metabolic complications:
>>Start from lipodystrophy,
>>dyslipidemia, insulin resistance
End up with cardiovascular diseases, stroke, DM
Prevalence of Dyslipidemia in a European cohort of HIV-infected children and adolescents (N=426), 60% receiving PI4
Fasting Hypertriglyceridemia66%
Hyper-cholesterolemia49%
Glucose intolerance5%
4%
21%
28%
1%
45%
Dyslipidemia found 40%-80% in children, associated with receiving PI and lipodystrophy1-3
1.Lapphra K. J Med Assoc Thai. 2005. 2. Taylor P. Pediatrics 2004. 3. Amaya RA. Pediatr Infect Dis J. 2002, 4. Alam NM. J Acquir Immune Defic Syndr. 2012 March 1; 59(3): 314–324
Frequency of abnormal lipid profile in Thai adolescentsSiriraj, Bangkok, 2013
He becomes an uneasy adolescent and start to have poor compliance to metformin and diet and weight control
- He continue to gain more weightBP: 130/90 mmHgTG = 202 mg/dl, HDL 52 mg/dl, Cholesterol 224 mg/dL
He becomes an uneasy adolescent and start to have poor compliance to metformin and diet and weight control
- He continue to gain more weightBP: 130/90 mmHgTG = 202 mg/dl, HDL 52 mg/dl, Cholesterol 224 mg/dL
Follow-up • FBS 400 mg/dl• HbA1C 13.8 %
Follow-up • FBS 400 mg/dl• HbA1C 13.8 %
Does he meet the criteria for metabolic syndrome? …..Yes or No
Does he meet the criteria for metabolic syndrome? …..Yes or No
Dx: DMStart Insulin SC
5 Years after starting treatmentAnd became a teenager
Metabolic Syndrome
A Cluster of Abdominal obesity Increased triglyceride levels Decreased HDL-cholesterol levels Hyperglycemia HypertensionA meta-analysis of the prospective studies has shown that the presence of metabolic syndrome increases the risk of Type2 DM and CVD
Galassi A. Am J Med. 2006
Metabolic Syndrome in children and adolescents: The clusters of metabolic risk factors (International Diabetes Federation)
Presence of metabolic syndrome increases risk of
- CVD (RR 1.53;
1.26-1.87)
- CHD(RR 1.52;
1.37-1.69)
- Stroke (RR 1.76;
1.37-2.25).
Galassi A. Am J Med 2006;119:812-9
International Diabetes Federation (IDF) Criteria for MS in Children
Age group
Obesity (WC) TG (mg/dl)
HDL-C (mg/dl)
BP (mmHg) BG (mg/dl)
6<10 ≥90th% tile
10<16 ≥90th% tile or adult cut-off
≥150 <40 Sys≥130 or Dias≥85
FBG ≥100 or T2DM
≥16 ≥90 cm in male,
≥80 cm in female
≥150 <40 in male,
<50 in female
Sys≥130 or Dias≥85
FBG ≥100 or T2DM
Zimmet P et al on Behalf of the International Diabetes Federation Task Force on Epidemiology and Prevention of Diabetes. Lancet 2007:369:2059-2061
Metabolic syndrome among HIV-infected patients: related factors
Pathogenesis of Metabolic Complications in HIV-infected Patients
HIV infection increase inflammatory cytokines TNF inhibits the uptake of FFA by adipocyte, increase
lipogenesis IL-6 and adipocytokines cause dyslipidemia and lipodystrophy May directly induce insulin resistance
Protease inhibitor Effect several steps causing dyslipidemia, IR, and
lipodystrophy NRTI
Cause mitochondrial dysfunctionlactic acidosis adipocyte death
Anuurad E. Curr Opin Endocrinol Diabetes Obes. 2010 Oct;17(5):478-85.
11β-HSD1, 11β-hydroxysteroid dehydrogenase type 1; FFA, free
fatty acids; ROS, reactive
oxygen species;
Development of HIV and PI associated lipodystrophy/ IR
Screening and intervention for
metabolic complications in HIV-
Infected Patients is needed especially
for patients at risk
Contribution of risks factors for CAD in HIV-Positive Persons
Rotger M. CID 2013 Jul;57(1):112-21.
1.04
1.25
1.47 Estimated effect (95%CI) on the odds ratio of a first CAD event for:- genetic risk score quartile (black dots), - HIV-related variables (gray triangles)- traditional CAD risk factors (gray squares).
Impaired FBS
Oral Glucose Tolerance Test (OGTT) • Glucose 1.75g/kg/dose (Max 75g)• Blood for Blood sugar and insulin • (at 0, 60, 120 min)
95th % for age, sex and height Adapted from ADA and EASD consensus 2009, Libman IM. 2007
How to treat LD?
• Stop using d4T (do not use d4T for > 6 months) >>
Phasing out d4T
• Avoid PI (may not be possible, or use ATV/r or DRV/r
• Medical: None is really effective and practical
• Liposuction for severe buffalo hump
• Filling therapy for facial lipoatrophy: may consider in
adults
Before After
Prevention of Metabolic Complicationsin HIV-Infected Children & Adolescents
Healthy life style weight control regular exercise low saturated fat diet, eat fish and veggies No smoking
Avoid PI (25% of Asian children are receiving PI) Serious with adherence to first line NNRTI
regimens, NVP has the least long-term problem Screening and early intervention in
borderline dyslipidemia
Cardiac dysfunction
Cardiomyopathy associated with severe
HIV diseases and improved with HAART.
However, long term ART may associated with
increased cIMT.
3 year- old girl with pneumonia and cardiomyopathy
• Echocardiogram before ART (14/6/2010)– Severe MR – LV dilatation with hypokinesia LV wall, LVEF 16%– Minimal pericardial effusion– Imp: Dilated cardiomyopathy with severe MR
The cIMT in association with on PI > 6 months in HIV-infected Thai adolescents
Low bone mass, Osteopenia and
Vitamin D deficiency
A 15 years old Thai boy with growth failure
• At 1 year-old, he had recurrent severe pneumonia, delayed development, and growth failure.
• At 5 year-old, he had pulmonary TB
• He always be very small despite successful antiretroviral therapy
Age Regimen CD4 VL
7 y AZT+3TC+EFV 45 >75,0000
8 y “ 461 26,400
11 y AZT+3TC+TDF+LPV/r
12 y “ 638 163
13 y “ 784 < 40
BMD Z-score
Adjust to height age (12 y)
0.721 -0.9
Adjust to Thai reference (15 y)
0.721 -2.1
DXA scan of lumbar spine (L2-L4)DXA scan of lumbar spine (L2-L4)
Bone densitometry (Dual-energy x-ray
absorptiometry; DXA) performed at 15 year-old
Both HIV and ARV Associated with Osteopenia: A -meta analysis
Brown TT. AIDS 2010;20:2165-74.
Bone Mass Accumulate From Childhood and Loss in Adulthood
Theintz G. J Clin Endocrinol Metab 1992;75:1060-5.
Rizzoli R. Osteoporos Int 1999;9 (suppl 2):S17-23.
Greatest bone mass gain at spine and hip is at:
- Girls: 11-14 yo. Tanner 2-4
- Boys: 13-17 yo. Tanner 4
Therefore, prevention of osteoporosis
and fracture must be started in
childhood
Bone mineral content is lower in prepubertal HIV-infected children
Arpadi SM. JAIDS 2002;29:450-4.
Age versus total body bone mineral content (TBBMC) adjusted for sex, race, height, and weight in HIV-infected (squares) and healthy (diamonds) prepubertal children.
Healthy
HIV+
Prevalence of low BMD measured by spine BMD (L2-L4) in Thai HIV-infected adolescents: The first study in Asia
Adjusted for Thai reference
Z-s
core
perc
en
tag
e
Puthanakit P. J Acquir Immune Defic Syndr. 2012 Aug 22
N=98%
%
%
%
BMD
HIV(gp120)
HIV (Tat)RANKLM-CSF
Osteoclastdifferentiation
CD4 T cells
Protease inhibitors
Other cells
RANKL, OPG
Osteoclast activity
Bone resorption
OsteopeniaOsteoporosis
- Low calcium intake- Vit D deficiency
Pathogenesis of osteoporosis in HIV-infected patients
TDF associated PRTD
Increased bone
turnover
Receptor activator of nuclear factor kappa-B ligand
Osteoprotegerin ligand
Vitamin D and clinical disease progression in HIV infection: EuroSIDA study
Viard JP. AIDS 2011:25:1305-15.
Kaplan–Meier estimation of progression. Kaplan–Meier estimation of progression to (a) AIDS-defining events, (b) all-cause mortality, and (c) non-AIDS-defining events according to 25(OH)D concentration tertile at baseline.
Association of Vitamin D Insufficiency - with Carotid Intima Media Thickness
- in HIV Infected Persons
Choi AI. CID 2011;0:1-4.
- AdjustedMean Carotid Intima Media Thickness by Vitamin D Category* A
f ter adj ustment for tradi ti onal cardi ovascul ar ri sk factors and
- HIV related factors, a gradedrelatio nship between vitamin D levels and
carotid IMT was observed, P5 .0 - 2 1 ). * Carotid intima media thick
ness predicted by the multivariable l inear regression model after adjust ment for age, sex, race, coronary he
artdisease,hypertensi on, dyslipidemia, pac- k years of smoking, NRTI duration, H
IVduration,season,totalcholesterol,LDL,waisttohi prati o,andcal ci umsup plementation,correctedcal ci um,al kal i ne phosphatase,
-parathyroidhormone, and 1 ,2 5 OHvitamin D level. Error bars repres
ent95%confidencei nterval s.
Association between initiation of antiretroviral therapy with efavirenz and decreases in 25-hydroxyvitamin D
Brown TT. Antiviral Therapy 2010;15:425-9.
• EFV induces CYP3A4 and CYP24, reducing CYP2R1, the enzyme involving in Vit D metabolism
Chokephaibulkit K. PIDJ 2013
In healthy children 19% were <20 ng/ml, and 60% were 20-30 ng/ml
Prevalence of vitamin D deficiency in Thai HIV-infected
adolescents: As High as Healthy Thai Children
25%
46%
29%
Deficiency Insufficiency
% Vitamin D category In HIV-infected adolescents
Reesukumal K. Clinical Chemistry 2012;58(10) Supplement:A153.
Kidney Dysfunction
Screening is important because
early renal diseases are asymptomatic
Incidence of new renal lab abnormalities was 3.7
events/100 child-years,
with rates increasing between 1993-2005
Andiman W et al. Pediatr Infect Dis J 2009;28:619-25
Incidence of Persistent Renal Dysfunction in Incidence of Persistent Renal Dysfunction in
HIV-Infected Children in PACTG 219/219cHIV-Infected Children in PACTG 219/219c
Incidence of Persistent Renal Dysfunction in Incidence of Persistent Renal Dysfunction in
HIV-Infected Children in PACTG 219/219cHIV-Infected Children in PACTG 219/219c
CKD defined as confirmed (persisting for 3 months) decrease in eGFR to 60
ml/min per 1.73m2 or less if eGFR at baseline above 60 ml/min per 1.73m2 or
confirmed 25% decrease in eGFR if baseline eGFR 60
ml/min per 1.73m2 or less).
Estimated chronic kidney disease and antiretroviral drug use in HIV-positive
patients
Estimated chronic kidney disease and antiretroviral drug use in HIV-positive
patients
Mocroft A. AIDS 2010;24:1667-78.
13 year-old girl died from CRF
• At 5 yo, presented with nephrotic syndrome responded well to HAART and steroid
• She has been virologic suppressed with normalized CD4 for more than 6 years
• At 12 yo, presented with renal failure required renal replacement with CAPD
• Experienced several peritonitis events and failed CAPD
• She was refused for hemodialysis and renal transplantationAn episode of HSV stomatitis
No chance for HIV-infected children with renal failure
Neuro-psychiatric issues
Impact of HAART on HIV encephalopathy among perinatally infected children and adolescents.
Patel K. AIDS 2009;23:1893-1901.Incidence of HIV encephalopathy and percentage of
children on HAART from 1994 to 2006.
Mental Health Disorders in HIV-Infected Children and Adolescents
• Review of 8 studies including 328 HIV-infected children age 4-21 years; prevalence compare with overall population
Scharko AM. AIDS Care 2006;18:441-5
24
29
25
0
5
10
15
20
25
30
35
ADHD Anxiety Dis Depression
Increased risk ratio 6x 3.8x 7.1xIncreased risk ratio 6x 3.8x 7.1x
percent
%
%%
Impact of HIV Severity on Cognitive and Adaptive Functi oning During Childhood and Adolescence
Smith R. PIDJ 2012;31:592-8.
Exposed uninfected
Infected w/o stage C
Infected w stage C
% impairment
A 13 Year-old Girl who suddenly became furious and angry with everything
Date Age Regimen CD4 VL Remark
no %
11/3/2003 8 yrs. 11 mo. StartAZT+3TC+EF
V
25 0.9 40,400
10/2/2004 9 yrs. 10 mo. “ 596 19 <400
8/1/2008 13 yrs. 9 mo. “ 1,052
42 <40 Wt. 35 kg. on EFV 400mg/dEFV Level=13,945 ng/ml
EFV reduced to 200 mg/ dayEFV Level=5,002 ng/mlSymptoms improved after dose reduction
16/6/2009 15 yrs. 2 mo. “ 912 35 <40
5/1/2010 16 yrs. 9 mo.
“ 1,171
44 <40
High levels of NVP and EFV may be found in 10% of Thai children
Nevirapine plasma exposure and CYP2B6 516 G>T polymorphisms after administration of GPO-VIR Z30 inHIV-infected Thai children
45% 45% 10%
Chokephaibulkit K. Antivir Ther 2011;16:1287-95
Rate
Without good screening and early intervention, it may end up with
premature age-related comorbidities
Premature Age-Related Comorbidities Among HIV-Infected Persons Compared With General Population
Guaraldi G. CID 2011;53:1120-6.
Comparative risk of hypertension, diabetes mellitus, renal failure, cardiovascular disease, and fracture, by age, among patients versus control subjects.
Prevention of long term treatment complications
• Start ARV early, prefer NNRTI for 1st regimen• Support adherence to the 1st line NNRTI regimens as
long as possible>> delayed PI use• Avoid long-term d4T• Use TDF only when no other alternative NRTI• Healthy life style
• Regular exercise, control weight
• Get enough sun light or vit D supplement
• Eat healthy, low saturated fat diet, eat fish and veggies
• Get enough calcium
• No addiction to drugs, games, tobacco, alcohol, etc
• Screen and early treat for metabolic complications, kidney (esp. TDF), liver, neuropsychiatric, and bone health (esp. TDF)
Most children and adolescents do not get enough calcium!
Greer FR. Pediatrics 2011;117:578-85.
Which children should be monitored BMD?
• May be before or during treatment regimens
with TDF or PI, especially with risks:
- Lean, small, or growth failure
- Have history of fracture with minimal trauma
But make sure to know how to interpret. Best is to use ethnic specific reference. The different machine do not give same results,
may need conversion
GE-Lunar = 1.195 x Hologic – 0.023 (Fan B, et al. Osteoporos Int (2010) 21:1227–1236.)
GE-Lunar = 1.195 x Hologic – 0.023 (Fan B, et al. Osteoporos Int (2010) 21:1227–1236.)