moabo201. xix international aids conference 2012
DESCRIPTION
Lipid profile in children randomized to immediate versus deferred nevirapine -based antiretroviral therapy in the PREDICT study. Kanjanavanit S , Puthanakit T , Kosalaraksa P, Hansudewechakul R , Ngampiyaskul C , Pinyakorn S , Luesomboon W, Saphonn V , Ananworanich J, Ruxrungtham K - PowerPoint PPT PresentationTRANSCRIPT
Lipid profile in children randomized to immediate versus deferred
nevirapine-based antiretroviral therapy in the PREDICT study
Kanjanavanit S , Puthanakit T , Kosalaraksa P, Hansudewechakul R , Ngampiyaskul C , Pinyakorn S ,
Luesomboon W, Saphonn V , Ananworanich J, Ruxrungtham K
and on behalf of the PREDICT study group
MOABO201.XIX International AIDS Conference 2012
PREDICT Study Design(2006 to 2011)
299 HIV-infected Thai and Cambodian childrenAged 1-12 years old, CD4 15-24%, no prior CDC C illnesses
Immediate ARTAZT/3TC/NVP
Deferred ART until CD4 < 15%
Randomized 1: 1
Outcomes at 144 weeksHigh AIDS-free survival rate (98%) in both arms
No differences in CDC B event rates between arms
Puthanakit T, 2011 IAS [TULBPE 023]
Objective
• To compare lipid profiles in children
randomized to immediate versus deferred
nevirapine-based antiretroviral therapy (ART)
Methods
• Data was collected in patients who first
started and continued antiretroviral
treatment with nevirapine – based regimen
1. Immediate ART group
2. Deferred starting ART group
3. Deferred not on ART group
Lipid measurement
• Patients > 4 hour fasting were included
• Lipid measurement : standard techniques with
automated chemistry analyzer
• LDL by calculation
Definition
• The abnormal lipid level was defined as
– Total cholesterol > 200 mg/dl
– LDL-Cholesterol > 130 mg/dl
– HDL-Cholesterol ≤ 40 mg/dl
– Triglyceride > 130 mg/dl
PACTG1045 study.AIDS 2009,23:661-672.National Cholesterol Education Program.Pediatrics1992;89:495-501.PACTG1045 study.AIDS 2009,23:661-672.
National Cholesterol Education Program.Pediatrics 1992;89:495-501.
Results
• Data were available for 263 participants – Group 1 immediate ART N= 129– Group 2 deferred starting ART N=60– Group 3 deferred not on ART N= 134
• Median(IQR0) age 6.5 (4.1-8.5) years• Male 42%• Median (IQR) of fasting time is 8 (8.5-9) hours
Clinical characteristics at week 0 and 144
ParametersWeek 0 Week 144
Immediate (n=129)
Deferred(n=134)
Immediate(n=94)
Deferred(n=127)
WAZ -1.3 -1.3 -1.3 -1.4
HAZ -1.6 -1.7 -1.5 -1.7
CD4% 19 20 34 24 *
CD4 cell/mm3 611 619 977 662 *HIV RNA, log10 copies/mL 4.9 4.7 1.7 3.4 *
Dyslipidemia % 59 67 37 61*
* p < 0.05
Lipid profile of immediate and deferred treatment to nevirapine-based ART
* p < 0.05* p < 0.05
* p < 0.05* p < 0.05
At week144 lipid profiles of NVP-based ART
Parameters median (IQR)mg/dL Dyslipidemia prevalence
Total cholesterol 166 (149-190) 15 %
Triglyceride 91 (69-113) 14 %
LDL 91 (78-107) 11 %
HDL 55 (48-67) 11 %
TC:HDL ratio 2.8 (2.5-3.6) ND
Treatment effects on lipid profiles
Lipid profilesImmediate VS
Deferred not starting ART* Immediate VS
Deferred starting ART*
Mean difference
95%CI p
Mean difference95%CI p
Total cholesterol 20.2 (15.9, 24.5) <0.001 3.2 (-2.1, 8.6) 0.24
Triglyceride -9.8 (-16.8, -2.8) 0.006 -8.1 (-16.2, 0.04) 0.05
LDL 9.1 (5.3, 12.9) <0.001 -0.7 (-4.0, 5.5) 0.76
HDL 13 (10.8, 15.3) <0.001 4.9 (2.1, 7.8) 0.001• Reference group• Results from multivariate models, adjusted for baseline of the given endpoints
and study week
Discussions
• ART Naïve HIV infected children randomized to NVP-
based treatment or deferred ART
– Long term FU data, mild immune suppression
– Low prevalence on dyslipidemia in treatment arm
– PI-based and EFV-based regimens have been associated
with higher rates of dyslipidemia than NVP-based
regimens • van Leth F.PLoS Medicine. 2004• Jean-Jacques Parienti. CID2007• Negredo E. CID2002• Lainka E. Pediatrics2002• Mankhatitham W. J Med Assoc Thai 2012
Discussions
• Overall dyslipidemia rate reduced from 64% to 37% in
immediate treatment arm where as the rate increased
to 78% in deferred not starting ART arm
• The randomized study design is a major strength;
however, low number and shorter duration of ART in
the deferred arm children limits longer-term
comparison.
Conclusions
• After 3 years of follow-up, nevirapine-based initiation
achieved favorable lipid profile in children with mild
to moderate HIV-associated immune deficiency
• Less dyslipidemia was found in treatment group
compared to deferred group
Acknowledgement Children and their families who participated in this study Funding
– US National Institutes of Health (NIAID, NICHD, NIMH) Antiretroviral supply
– GSK/ViiV Healthcare (AZT, 3TC, ABC), Boehringer (NVP), Merck (EFV), Abbott (LPV/r), Roche (NFV)
Endpoint Review Committee members, Data Safety Monitoring Board members Investigators and site staffs Thailand
– HIV-NAT, Thai Red Cross AIDS Research Center, Bangkok– Bamrasnaradura Infectious Diseases Institute, Nonthaburi– Srinagarind Hospital, Khon Kaen University, Khon Kaen– Queen Savang Vadhana Memorial Hospital, Chonburi – Nakornping Hospital, Chiang Mai – Chiangrai Prachanukroh Hospital, Chiang Rai– Prapokklao Hospital, Chantaburi
Cambodia– National Pediatric Hospital, Phnom Penh– Social Health Clinic, Phnom Penh