Early vs. deferred ART in HIV infected infants : a European Collaborative Cohort

Study

Early vs. deferred ART in HIV infected infants : a European Collaborative Cohort

Study

European Infant Collaboration

Study questionIs there a benefit to treat all infants who are vertically infected with HIV and followed up from birth, even if they are asymptomatic?

STUDY POPULATIONSTUDY POPULATION

327 infants

No neonatal prophylaxis68

Neonatal prophylaxis259

HIV infected diagnosed < 3 months216

Diagnosed HIV > 3 months43

AIDS < 3 months4

Lost FU < 3 months2

AIDS free at 3 months210

EIC, 2007

DATA COLLECTIONDATA COLLECTION

Cohorts Number of centres in cohort

Number of children

Number of children included

France 36 96 83

Italy 21 53 23

UK and Ireland 16 52 38

Spain 8 31 17

ECS & PENTA 5 20 10

Belgium 4 20 16

Poland 1 17 8

Switzerland 6 15 7

Romania 1 9 1

Netherland (Amsterdam)

1 6 3

Germany (Munich)

1 5 2

Netherland (Rotterdam)

1 3 2

Total 101 327 210

EIC, 2007

AGE AT INITIATION OF ART (n=210)

AGE AT INITIATION OF ART (n=210)

EIC, 2007

124

86

AGE AT FIRST ART TREATMENT BY COHORT

Age at first ART (months)60,0054,0048,0042,0036,0030,0024,0018,0012,006,000,00

On

e M

inu

s C

um

Su

rviv

al

1,0

0,9

0,8

0,7

0,6

0,5

0,4

0,3

0,2

0,1

0,0

Other-censoredCHIPS-censoredITALY-censoredEPF-censoredOtherCHIPSITALYEPFLocal cohorts

Early treatment (n=124)

Deferred treatment

(n=86)

P

Sub Saharan African ethnicity

56% 57% 0.9

Gender female 61% 61% 0.9

ART during pregnancy 51 % 62 % 0.08

Caesarean delivery 55% 55% 0.94

Birth weight <2500g 31% 23% 0.21

Premature delivery (<37 wk) 21% 22% 0.82

Breast feeding 2% 6% 0.12

Number of drugs in the first ART 1 or 2 3 4

23%69%9%

13%73%14%

0.17

Class of drugs in 1st ART1 or 2 NRTIPI +NNRTI +other

22%42%25%11%

14%50%31%5%

0.11

CHARACTERISTICS OF INFANTS BY GROUP

CHARACTERISTICS OF INFANTS BY GROUP

EIC, 2007

crude HR= 5.095% CI: 2.0-12.6 p<0.001

KAPLAN MEIER AIDS/DEATH FREE SURVIVAL IN INFANTS ON EARLY AND DEFERRED ART

KAPLAN MEIER AIDS/DEATH FREE SURVIVAL IN INFANTS ON EARLY AND DEFERRED ART

EIC, 2007

CUMULATIVE RISK OF AIDS/DEATH BY COHORT (24 EVENTS)

Age (months)60,0054,0048,0042,0036,0030,0024,0018,0012,006,000,00

On

e M

inu

s C

um

Su

rviv

al

0,40

0,35

0,30

0,25

0,20

0,15

0,10

0,05

0,00

Other-censoredCHIPS-censoredITALY-censoredEPF-censored

Local cohorts-censored

OtherCHIPSITALYEPFLocal cohorts

CONCLUSIONS

Etude collaborative européenne multicentriquePériode d’étude : Enfants nés entre 1996 et 2004

Parmi les 210 nourrissons, suivis depuis la naissance ayant bénéficié d’une prophylaxie néonatale, chez qui un diagnostic d’infection à VIH a été porté avant l’âge de 3 mois et qui à 3 mois n’avaient pas présenté de symptômes, moins de 2 % des 124 enfants traités avant 3 mois versus près de 12 % des 86 enfants traités après 3 mois ont évolué vers SIDA ou décès avant l’âge de 12 mois (HR de 5).

EIC COLLABORATORS

Madrid, Spain

Brussels, Belgium

EPF INSERM, France J. Warszawski, J. Le ChenadecC. Dollfus

MRC CTU, UK

K. Boyd, A. Judd,H. GreenS. WalkerDM. Gibb,

Italian Register L. Galli, C. GabianoPA. TovoM. De Martino

J. RamosS. Guillen Martin

ECS, UK C. Thorne, D.Patell

C. Giaquinto

Warsaw, Poland M. MarczynskaJ. Popielska

Swiss HIV Cohort O. KeiserC. RudinD. Nadal

Bucharest, RomaniaL. EneD. Duiculescu

Amsterdam, The Netherlands: H. ScherpbierE. Le Poole

Munich, GermanyU. WintergerstG. Nothiers

Liège, Belgium V. Schmitz

Rotterdam, The NetherlandsG. VerweelR. De GrootN. Hartwig Padova, Italy

T. Goetghebuer, E. Haelterman, M.Hainaut, B. BrichardJ. Levy

CHER TRIAL Part A n= 375

HIV infection diagnosed before 12 weeks and CD4% >25%

Arm 1

Deferred treatment

N=125

Arm 2

Short course

(to first birthday)

N=125

Arm 3 Long course

( to second birthday)

N=125

FOLLOW UP For a minimum of 3.5 years

ART (start or re-start) when CD4% <20% or clinical event

(<25% from August 2006)

BASELINE CHARACTERISTICS

Variable Arm 2 & 3 Arm 1

Number of participants enrolled 252 125

Sex: Female (%) 147 (58.3 %) 74 (59 %)

Age (weeks, median (IQR) 7.4 (6.6 - 8.9) 7.1 (6.4 - 8.9)

Mother receiving ART for PMTCT

No Therapy 26 (10.3 %) 15 (12 %)

NVP (%) 162 (64.3 %) 72 (58 %)

AZT (%) 8 (3.2 %) 5 (4 %)

AZT + NVP (%) 51 (20.2 %) 26 (21 %)

HAART (%) 2 (0.8 %) 5 (4 %)

Weight (Median IQR (kg) 4.4 (4.0 - 4.9) 4.5 (4.0 - 5.0)

CDC Classification

Class N & A (%) 237 (94.0 %) 121 (96.8 %)

Class B (%) 11 (4.4 %) 3 (2.4 %)

CD4 % (median (IQR) 35.1 (29.1 - 40.8) 35.6 (29 -43.8)

CD4 Count (cells/mm3) median (IQR) 2035 (1519-2754) 2044 (1585-2960)

5985 babies were screened using DNA PCR to enrol 377 HIV pos infants

MORTALITY RATES

Variable Arm 2 & 3n = 252

Arm 1n = 125

Totaln = 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

DISEASE PROGRESSION IN ALL PATIENTS

Variable Arm 2 & 3n = 252

Arm 1n = 125

Total

Failure to thrive 18 19 37

Developmental delay 0 8 8

PCP 0 5 5

Oesophageal candidiasis 0 2 2

Extrapulmonary TB 1 1 1

CMV colitis 0 1 1

CMV pneumonia 0 2 2

CMV HepatitisPneumococcal disease

00

12

12

Number EventsNumber patients

1919

4138

6057

SUMMARY & CONCLUSIONS

Starting ART before 12 weeks of age reduces early mortality by 75%

Findings have implications for guidelines on timing of ART in early infancy

These results support the need for enhanced pMTCT programmes, early infant diagnosis and effective transition to care.