Response to early antiretroviral treatment in HIV-infected infants: the experience of the European Pregnancy & Paediatric HIV Cohort Collaboration (EPPICC) Dr Claire Townsend on behalf of EPPICC
Background Paediatric treatment guidelines now recommend initiation of ART in all HIVinfected infants regardless of clinical status, CD4 or viral load. Data on short-term immunological and virological responses to early treatment are limited.
Aims To describe first-line HAART regimens in infants in Europe. To investigate virological and immunological response to HAART at 6 and 12 months after initiation. Inclusion criteria: Born 1996-2008 Diagnosed with HIV & started HAART <12m of age 9 months of follow-up
9 cohorts, 414 children Data n Percent UK / Ireland (NSHPC/CHIPS) 158 38% Italy (Italian Register) 94 23% France (EPF) 75 18% Others * 87 21% * Belgium (Hopital St Pierre), Romania (Victor Babes Hospital), Spain (CoRISPE-cat, Catalonia; Madrid Cohort), Switzerland (MoCHiV); European Collaborative Study.
Analysis Virological response / suppression Viral load <400 copies/ml Logistic regression CD4 response Absolute change in CD4 z-score from baseline Linear regression A priori predictors Type of HAART Age at initiation (<3, 3-5, 6+ months) Calendar year of initiation (1996-2008)
Baseline Characteristics (n=414) Percent Female 54% <3 38% Age at HAART initiation 3-5 37% (months) 6+ 24% Maternal ART in pregnancy 34% Infant neonatal prophylaxis 28% Breastfed 36% Pre-treatment AIDS diagnosis 29%
Trends in first-line HAART regimens 100% 11% 12% 6% 8% 80% 20% 60% 40% 66% 40% 8% 15% 41% 24% 20% 20% PI+NNRTI/Other unboosted PI boosted PI NNRTI + 3 NRTIs NNRTI + 2 NRTIs 20% 0% 30% 25% 30% 19% 1996-99 2000-02 2003-05 2006-08 Year of HAART initiation
Proportion of children achieving virological suppression after 12 months of HAART % viral load<400c/ml 100% 90% 80% 70% 60% 50% 40% 30% 20% 10% 0% 52% 56% 71% 85% 1996-99 2000-02 2003-05 2006-08 Year of HAART initiation
Virological response at 12 months after HAART initiation - multivariable analysis (n=326) n AOR 95% CI p-value Year of HAART initiation per year 326 1.2 1.0, 1.3 <0.01 Type of HAART NNRTI + 2NRTIs 80 1.0 NNRTI + 3NRTIs 52 2.7 1.1, 6.8 Boosted PI 43 0.9 0.4, 2.3 Unboosted PI 119 0.7 0.4, 1.2 PI+NNRTI / neither 32 0.5 0.2, 1.3 0.01 No association with any other variables (age at initiation, cohort, gender, ethnic group, pre-treatment AIDS / CD4 z-score / viral load, maternal ART, neonatal prophylaxis, breastfeeding)
Change in CD4 z score after 12 months of HAART by baseline CD4 z score CD4 zscore increase (12m) -5 0 5 10 CD4 z-score increase by 12m Median CD4 z-scores Baseline -1.5 (IQR -3.5, -0.5) 12 months -0.5 (IQR -1.3, 0.1) Increase 1.0 (IQR -0.3, 2.8) -10-5 0 5 baseline CD4 zscore Baseline CD4 z-score
Change in CD4 z-score at 12 months after HAART initiation - multivariable linear regression (n=177) Coeff. 95% CI p-value Baseline CD4 z-score Per unit -0.8-0.9, -0.7 <0.001 Maternal ART in pregnancy No / not reported 0.0 Yes -1.0-1.5, -0.5 <0.001 No association with any other variables (HAART type, calendar year, age at initiation, gender, ethnic group, pre-treatment AIDS / viral load, neonatal prophylaxis, breastfeeding)
Conclusions Virological response to treatment improved substantially over time General improvements in HIV management and care Some differences in virological response by type of HAART Effectiveness of 4-drug regimens (ARROW trial) Baseline CD4 z-score was the main predictor of CD4 response
Further work Further analyses will explore duration of first-line regimens and reasons for stopping/switching treatment European experience of early HAART over 13 years Similar patterns in unselected populations where all children receive HAART?
Acknowledgements Writing Committee: Ali Judd and Martina Penazzato (projects leads), Hannah Castro and Claire Townsend (statisticians), Elena Chiappini and Luisa Galli (Italian Register for HIV Infection in Children), Diana Gibb (UK and Ireland Collaborative HIV Paediatric Study- CHIPS), Tessa Goetghebuer (Hopital St Pierre Cohort, Brussels, Belgium), Josiane Warszawski (French Perinatal Cohort- ANRS CO1 EPF). Contributing Cohorts: CHIPS (UK and Ireland); CoRISPE-cat (Catalonia, Spain); ECS (European Collaborative Study); Hopital St Pierre Cohort (Brussels, Belgium); ANRS CO1 EPF (France); Italian Register for HIV Infection in Children; Madrid Cohort of HIV-infected Children and Spanish Perinatal Cohort Study (Spain); MoCHiV (Swiss Mother and Child HIV Cohort Study); NSHPC (National Study of HIV in Pregnancy and Childhood, UK and Ireland); Victor Babes Hospital Cohort (Romania). EPPICC Cohorts Collaborators: Diana Gibb (CHIPS); Niels Valerius (Copenhagen Cohort, Denmark); Antoni Noguera-Julian (CoRISPE-cat); Claire Thorne (ECS); Tessa Goetghebuer (Hopital St Pierre Cohort); Josiane Warszawski (ANRS CO1 EPF); Vana Spoulou (Greece Cohort); Chris Koenings (KompNet, Germany); Maurizio de Martino (Italian Register); Jose T Ramos (Madrid Cohort of HIV-infected Children, and Spanish Perinatal Cohort Study); Mark Lallemant (PHPT, Thailand); Christoph Rudin (MoCHiV); Pat Tookey (NSHPC); Carlo Giaquinto (PENTA, Italy); Luminita Ene (Victor Babes Hospital Cohort); Magda Marczynska (Warsaw Cohort, Poland).