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IAS 2013, Kuala Lumpur, Malaysia Late Breaker Track A, Wednesday 3 July WELBA02

Naive CD4 T lymphocytes and recent thymic emigrants, 15 or more years after perinatal HIV infection The ANRS-EP38-IMMIP study.

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IAS 2013, Kuala Lumpur, Malaysia Late Breaker Track A, Wednesday 3 July WELBA02

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  1. Naive CD4 T lymphocytes and recent thymic emigrants, 15 or more years after perinatal HIV infection The ANRS-EP38-IMMIP study Stéphane Blanche, Daniel Scott-Algara, Jérôme Le Chenadec, Céline Didier, Thomas Montange, Véronique Avettand-Fenoel, Christine Rouzioux, Jean-Paul Viard, Catherine Dollfus, Naima Bouallag, Josiane Warszawski, Florence Buseyne IAS 2013, Kuala Lumpur, Malaysia Late Breaker Track A, Wednesday 3 July WELBA02

  2. ANRS-EP38-IMMIP study • A physiopathological study focusing on patients with perinatal HIV infection born at the start of the epidemic (before 12/1993) Did not have early access to HAART 60% are alive and in regular follow-up (French birth cohort, 2010) Now: young adults and older patients with a pediatric history of HIV disease • Aim: to improve our knowledge of the virological and immunological status of adolescents and young adults infected during the perinatal period

  3. ANRS-EP38-IMMIP : study design 2007-2009 n=93 HIV in perinatal period >15 years 1 25 ml Current immune and virological status Since Birth In care before 1996 > 15 ans Lifetime HIV disease CD4/HIV-RNA/ Treatment 2 HIV disease correlates

  4. Patients' characteristics

  5. Patients’ HIV disease history over life time, except for plasma HIV-RNA (available since 1996)over the last 10 years

  6. Periphery Thymus Adapted from Kohler, Blood 2009 Naive T lymphocytes and thymic activity The size of the naive T-cell compartment determines the diversity of the T-cell repertoire and is thus critical to provide immunity to foreign antigens → % naive CD4 T lymphocytes (among total peripheral blood CD4 T cells ) Naive T cell production - De novo in the thymus = recent thymic emigrants (RTE, CD31+) - homeostatic proliferation in the periphery (CD31-) reduced T-cell repertoire diversity → % of CD31+ RTE among naive CD4 T-lymphocytes : a marker of thymic activity

  7. Current HIV RNA level CD4N CD4RTE Median(IQR): 56% (44-64) Median(IQR): 79% (74-83) Aviremic Viremic Aviremic Viremic Levels similar to those of uninfected patients CD4N CD4RTE CD4RTE Higher CD4RTE % in viremic than in aviremic patients

  8. Current CD4 cell levels CD4N CD4RTE aviremic: r=0.431, P=0.001 viremic: r=0.387, P=0.04 aviremic: r=0.520, P=0.0007 viremic: r=0.022, P=0.93 CD4RTE Positively correlated to CD4 cell counts CD4N

  9. Past HIV disease (aviremic patients) Cumulative viremia Coreceptor Duration CD4%<15% CD4N R5 X4R5 CD4RTE R5 X4R5 Positive correlation with cumulative viremia over the past 10 yrs Higher in patients with X4R5 strains than in those with R5 strains CD4N Negative correlation with lifetime duration of CD4% < 15% CD4RTE Cumulative viremia : time updated Area Under the Curve of viral load (Zoufaly et al., 2009) Coreceptor usage : sequence analysis of HIV DNA env, using SVMGeno2pheno algorithm

  10. No association with: Other HIV disease parameters Age CDC stage CTreatment history Ethnicity HIV subtype CD4RTE % were higher in female than in male patients

  11. Multivariate models : a summary aviremic patients CD4N CD4RTE

  12. Conclusions In patients included in the ANRS-EP38-IMMIP study: • CD4N and CD4RTE levels were in the range reported for healthy adolescents/young adults • CD4N and CD4RTE levels were directly correlated with CD4 cell count • Paradoxical associations between CD4N and CD4RTE percentages and current and/or past HIV replication levels • Enhanced thymopoiesis appears to compensate for high rates of HIV-driven T-cell depletion • Observed in several pediatric studies, and some adults studies (early asymptomatic phase) • In most adults, thymopoeisis is reduced by viral replication • The thymus remains active but … is not without damage after periods of immunosuppression

  13. Acknowledgments To all patients who agreed to participate in this study. To the investigators of the ANRS-EP38-IMMIP and staff members Principal Investigator : Pr Stéphane Blanche Methodology : Dr Josiane Warszawski Virology : Pr Christine Rouzioux Immunology : Dr Daniel Scott-Algara, Dr Florence Buseyne

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