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V. Avettand-Fenoel, S. Blanche, J. Le Chenadec,

The cell-associated HIV-1 DNA level 15 years after of perinatal infection is strongly correlated with lifetime viral replication The ANRS-EP38-IMMIP Study. V. Avettand-Fenoel, S. Blanche, J. Le Chenadec, C. Dollfus, D. Scott-Algara, J.-P. Viard, N. Bouallag,

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V. Avettand-Fenoel, S. Blanche, J. Le Chenadec,

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  1. The cell-associated HIV-1 DNA level 15 years after of perinatal infection is strongly correlated with lifetime viral replication The ANRS-EP38-IMMIP Study V. Avettand-Fenoel, S. Blanche, J. Le Chenadec, C. Dollfus, D. Scott-Algara, J.-P. Viard, N. Bouallag, Y. Benmebarek, Y. Rivière, J. Warszawski, C. Rouzioux, F. Buseyne XVIII International AIDS Conference Vienna, 18-23 July 2010 Treatment of Children: HIV in Children, Prognosis and Outcomes of TreatmentMonday, 19 July 2010 Abstract number MOAB0201

  2. ANRS-EP38-IMMIP study : aims and design • Characteristics of patients • Associations between the cell-associated HIV DNA level and the HIV disease history

  3. Background • The success of treatment of pediatric HIV has transformed the disease into a stable chronic condition • HIV-infected children enter into adulthood • New challenges for clinical management emerge • Several specificities of pediatric infection preclude an extrapolation from data of adults • Viral replication during ontogenesis of the immune system • High thymic activity during the first years of life • Limited availability of pediatric ARV formulations • Adherence issues

  4. Aims of the ANRS-EP38-IMMIP study • Describe the immunological and virological status of perinatally infected patients who are over 15 yrs old • Study their associations with : • The current status (CD4/Virological/Clinical/Therapeutic) • The status at time of HAART initiation (CD4/Virological/Clinical/Therapeutic) • The duration of specific conditions (controlled viremia/immunosuppression/treatment)

  5. Study design • Inclusion of 93 perinatally HIV-infected patients more than 15 years old with unchanged therapeutic status for at least 6 months • Patients were followed from birth in the French Pediatric Cohort ANRS CO10 (n=68), or care was initiated before 1996 (n=25). • CD4, virological, clinical and therapeutical data collected since birth/beginning of follow-up • A blood sample was taken for biological evaluations. The HIV DNA level in PBMCs was quantified by real-time PCR (ANRS assay, Biocentric, Bandol) for 91 patients (Avettand-Fenoel et al., 2009)

  6. Patients’ characteristics-1

  7. Patients characteristics-2

  8. The HIV RNA level and CD4 cell count according to current treatment HIV RNA CD4 cell count Median : 422 612 % undectable : 0 75

  9. The cell-associated HIV DNA level • Predictor of HIV transmission and disease progression, independently of the HIV RNA level and CD4 counts (Kostrikis et al., 2002; Tierney et al., 2003; Rouzioux et al. 2005; Goujard et al. 2006; Lehman et al. 2007) • Predictor of viral control under HAART De Rossi et al. 2002 , Saitoh et al. 2002 , Yerly et al. 2004, Hatzakis et al. 2004,Havlir et al. 2005Hoen et al. 2007, Sarmati et al. 2007) • Indicator of the level of cellular reservoirs • In clinical practice, total (unintegrated and integrated) HIV DNA level is • easy to quantify • a marker of viral level in HAART treated patients with undetectable HIV RNA

  10. Associations between life time HIV disease history and current HIV DNA level Current HIV DNA Birth / before 1996 > 15 ans CD4 HIV RNA Clinical events Treatment Wilcoxon 2-sided test Spearman correlation Linear regression

  11. Socio-demographic characteristics and current HIV DNA level

  12. Current HAART is associated with lower HIV DNA level Age rho=-0.07, p=0.49 Current HAART p<0.05 Median : 3.2 2.8

  13. Current HIV RNA level and CD4 cell counts are correlated to the HIV DNA level HIV RNA rho = 0.46, p<0.0001 CD4 count rho=-0.36, p=0.0006

  14. Cumulative virological history • Duration of HIV RNA < 500 copies/mL • Cumulative viremia : time updated Area Under the Curve of viral load • Predictive of AIDS-related lymphoma in HAART treated adults (Zoufaly et al., 2009) • Predictive of AIDS/Death in untreated adults (Cole et al., 2010) • Calculated as described by Zoufaly et al. (2009) over the last 10 years

  15. Duration of undetectable HIV RNA and cumulative viremia are correlated to the HIV DNA level Cumulative viremia rho=0.50, p<0.0001 Duration HIV RNA <500 copies/mL rho =- 0.48, p<0.0001

  16. Cumulative HAART duration is correlated to the HIV DNA level Cumulative HAART duration rho=-0.30, p<0.006

  17. Summary of univariate analysis HAART initiation Current status Yes Birth / before 1996 > 15 ans Current HIV DNA CD4 history Cumulative HIV RNA Cumulative HAART Cumulative all ARV Yes Yes Sex CDC stage C Geographic origin Yes?

  18. Multivariate analysis

  19. Conclusions • Significantly higher HIV DNA levels in female subjects • Only the cumulative HIV RNA level over the past 10 years remained significantly associated to the HIV DNA level • In perinatally HIV-1-infected adolescents and young adults, the cell-associated HIV DNA level reflects the control of virus over time

  20. Acknowledgments To all patients who agreed to participate in this study. To the investigators of the ANRS-EP38-IMMIP and staff members To the ANRS and  Fondation AREVA

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