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 difference95%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