1. 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

2. PREDICT Study Design (2006 to 2011) 299 HIV-infected Thai and Cambodian children Aged 1-12 years old, CD4 15-24%, no prior CDC C illnesses 299 HIV-infected Thai and Cambodian children Aged 1-12 years old, CD4 15-24%, no prior CDC C illnesses Immediate ART AZT/3TC/NVP Immediate ART AZT/3TC/NVP Deferred ART until CD4 < 15% Deferred ART until CD4 < 15% Randomized 1: 1 Outcomes at 144 weeks High AIDS-free survival rate (98%) in both arms No differences in CDC B event rates between arms Puthanakit T, 2011 IAS [TULBPE 023]

3. Objective To compare lipid profiles in children randomized to immediate versus deferred nevirapine-based antiretroviral therapy (ART)

4. 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

5. Lipid measurement Patients > 4 hour fasting were included Lipid measurement : standard techniques with automated chemistry analyzer LDL by calculation

6. 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.

7. 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

8. Clinical characteristics at week 0 and 144 Parameters Week 0Week 144 Immediate (n=129) Deferred (n=134) Immediate (n=94) Deferred (n=127) WAZ-1.3 -1.4 HAZ-1.6-1.7-1.5-1.7 CD4%19203424 * CD4 cell/mm3 611619977662 * HIV RNA, log10 copies/mL 4.94.71.73.4 * Dyslipidemia %59673761* * p < 0.05

9. Lipid profile of immediate and deferred treatment to nevirapine-based ART * p < 0.05

10. At week144 lipid profiles of NVP-based ART Parametersmedian (IQR)mg/dL Dyslipidemia prevalence Total cholesterol166(149-190)15 % Triglyceride91(69-113)14 % LDL91(78-107)11 % HDL55(48-67)11 % TC:HDL ratio2.8(2.5-3.6)ND

11. Treatment effects on lipid profiles Lipid profiles Immediate VS Deferred not starting ART* Immediate VS Deferred starting ART* Mean difference 95%CI p Mean difference 95%CI p Total cholesterol 20.2 (15.9, 24.5)<0.0013.2 (-2.1, 8.6)0.24 Triglyceride-9.8 (-16.8, -2.8)0.006-8.1 (-16.2, 0.04)0.05 LDL9.1 (5.3, 12.9)<0.001-0.7 (-4.0, 5.5)0.76 HDL13 (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

12. 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

13. 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.

14. 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

15. Acknowledgement nChildren and their families who participated in this study nFunding – US National Institutes of Health (NIAID, NICHD, NIMH) nAntiretroviral supply – GSK/ViiV Healthcare (AZT, 3TC, ABC), Boehringer (NVP), Merck (EFV), Abbott (LPV/r), Roche (NFV) nEndpoint Review Committee members, Data Safety Monitoring Board members nInvestigators and site staffs nThailand – 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 nCambodia – National Pediatric Hospital, Phnom Penh – Social Health Clinic, Phnom Penh