Abstract

The cell-associated HIV-1 DNA level after 15 years of perinatal infection is strongly correlated with lifetime viral replication - The ANRS-EP38-IMMIP Study

Presented by Florence Buseyne (France).

V. Avettand-Fenoel¹, S. Blanche¹, J. Lechenadec², C. Dollfus³, D. Scott-Algara⁴, J.-P. Viard¹, N. Bouallag², Y. Benmebarek², Y. Rivière⁵, J. Warszawski^2,6, C. Rouzioux¹, F. Buseyne<sup>5

1</sup>Université Paris Descartes, EA3620, Hôpital Necker-Enfants malades, AP-HP, Paris, France, ²CESP INSERM U1018, Le Kremlin-Bicêtre, France, ³Hôpital Trousseau, Paris, France, ⁴Institut Pasteur, Unité de Régulation des Infections Rétrovirales, Paris, France, ⁵Institut Pasteur, Laboratoire d'Immunopathologie virale, Paris, France, ⁶Université Paris-Sud, Le Kremlin-Bicêtre, France

Background: The virological and immune status of perinatally infected adolescents and young adults has been poorly characterized. The cell-associated HIV-DNA level is both an indicator of the level of cellular reservoirs and an independent predictor of disease progression. We aimed here to study the HIV-1 DNA level at 15 years or more in relation to lifetime viral replication and treatment history.
Methods: In 2007-09, the ANRS-EP38-IMMIP study included 93 perinatally HIV-infected patients with unchanged therapeutic status for at least 6 months, followed since birth in the French Pediatric Cohort ANRS CO10, or who initiated care before 1996. A blood sample was taken for biological evaluations. HIV-DNA was quantified by real-time PCR (ANRS assay) for 91 patients.
Results: Among the 91 patients, 43% were male. Median age was 17 years (IQR:2.5-3.2). 14% of patients were off HAART. In the whole group, 65% of patients had undetectable HIV-RNA (< 80 copies/ml), median CD4 cell count was 588/µl (IQR:421-800), and median HIV-DNA load was 2.84 (IQR:2.51-3.17) log copies/10⁶ PBMC. Among currently treated and untreated patients, HIV-RNA was undetectable in 76% and 0% (p< 0.0001), median CD4 cell count was 616 and 424/µl (p< 0.008), and median HIV-DNA levels was 2.83 and 3.15 log copies/10⁶ PBMC (p< 0.05), respectively. HIV-DNA was correlated negatively with current CD4 cell count (R spearman:-0.34; p=0.001), cumulative duration of HAART (R:-0.29,p=0.006) and positively with CD8 cell count (R:0.33,p=0.003) and HIV-RNA (R:0.44,p< 0.001). HIV-DNA was correlated with cumulative HIV-RNA load over the last 10 years (R:0.54,p< 0.001). In multivariate analysis, the association between HIV-DNA and cumulative HIV-RNA viremia remained significant, after adjustment for current HIV-RNA detectability, current HAART and cumulative duration of HAART.
Conclusions: These are the first data describing HIV-DNA levels after 15 years of perinatal infection. HIV-DNA was strongly correlated with level of lifetime HIV-RNA and reflects the viral control over time.