179-HIV-I Pathogenesis and Predictors of Antiretroviral Response in Treatment and Prevention
Tuesday, Sep 11, 2012, 11:15 AM - 1:15 PM
H-1570a - Poor CD4+ T Cell Restoration Linked to Residual HIV-1 Reverse Transcription under AntiRetroviral Therapy
Tuesday, Sep 11, 2012, 11:30 AM - 1:30 PM
HIV Infections/immunology ; HIV testing
K. C. Psomas, MD (Doctor of Medicine) -
Fellow of Infectious Diseases
, C. Mettling, PhD -
, J. Reynes, MD, PhD -
, P. Corbeau, MD, PhD -
Infectious Diseases Dept., Univ. Hosp. of Montpellier, Montpellier, France,
Inst. of Human Genetics, CNRS UPR 1142, Montpellier, France,
Inst. of Human Genetics CNRS UPR 1142, Montpellier, France.
K. C. Psomas,
Impaired CD4+ T (T4) cell restoration in aviremic HIV-1 infected subjects under AntiRetroviral Therapy (ART) could be explained by ongoing de novo infection. Indeed, even abortive HIV infection induces inflammation and T4 cell apoptosis in lymphoid tissue. We propose a method detecting linear HIV DNA in the cytoplasma of T4 cells ; since its half life is short, it can be a reliable marker of recent infection.
We collected T4 cells of 33 treated patients with an HIV RNA level below 50 copies/mL. After subcellular fractionation we looked by nested qPCR for the presence of HIV DNA in the cytoplasma of cells. To exclude false positive due to contamination of the cytoplasmic by the nuclear extract, we checked that the ratio (number of copies in the cytoplasma : number of copies in the nucleus) was significantly higher for HIV DNA than for CCR5 DNA.
We detected the presence of HIV DNA in the cytoplasma of T4 cells in 10 patients. T4 cell gain was lower in these subjects (means of -4 [95% confidence interval (CI) -15, 7] T4 cells per month) than in the 23 other subjects (means of +13 [95% CI 3, 23] T4 cells per month, p = 0.035). We also measured the overexpression of the activation marker CD38 at the surface of CD8+ T cells in a subgroup of 20 patients. Globally, the percentage of activated CD8+ T cells increased in patients in which we detected cytoplasmic HIV DNA (means of +1.7% [95% CI -0.7%, +4.0%] monthly) and decreased in the patients in which we did not (arithmetic means of -0.5% [95% CI -1.6%, +0.7%] monthly, p = 0.052).
These data argue for a role of ongoing HIV infection in persistent immune activation and in the lack of immune restoration in some virologic responders. The proportion of aviremic subjects with de novo infection is consistent with the data obtained by Buzon et al. using another approach. Our assay could be used to monitor ART simplification, to determine in which patients ART intensification could be beneficial, and to discriminate ongoing infection from other causes of poor T4 cell restoration.
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