Unintegrated HIV-1 provides an inducible and functional reservoir in untreated and highly active antiretroviral therapy-treated patients-1

<p><b>Copyright information:</b></p><p>Taken from "Unintegrated HIV-1 provides an inducible and functional reservoir in untreated and highly active antiretroviral therapy-treated patients"</p><p>http://www.retrovirology.com/content/4/1/60</p><p>Retrovirology 2007;4():60-60.</p><p>Published online 29 Aug 2007</p><p>PMCID:PMC2048509.</p><p></p>vated in four experiments (nos. 1, 2, 3, and 4) or directly polyclonaly activated and cultured with L-731,988 in two other assays (nos. 3 and 4). . latently infected resting CD4T cells were directly polyclonaly activated or preincubated 2 days before polyclonal activation in two experiments (nos. 3 and 4)

Unintegrated HIV-1 provides an inducible and functional reservoir in untreated and highly active antiretroviral therapy-treated patients-5

<p><b>Copyright information:</b></p><p>Taken from "Unintegrated HIV-1 provides an inducible and functional reservoir in untreated and highly active antiretroviral therapy-treated patients"</p><p>http://www.retrovirology.com/content/4/1/60</p><p>Retrovirology 2007;4():60-60.</p><p>Published online 29 Aug 2007</p><p>PMCID:PMC2048509.</p><p></p> 13 and 14) using -LTR real-time PCR experiments. CD4T cells that were directly stimulated, preincubated 1 and 2 days before polyclonal activation, and directly stimulated and cultured with L-731,988 were recovered from ELISpot assays and tested in PCR experiments

Unintegrated HIV-1 provides an inducible and functional reservoir in untreated and highly active antiretroviral therapy-treated patients-7

<p><b>Copyright information:</b></p><p>Taken from "Unintegrated HIV-1 provides an inducible and functional reservoir in untreated and highly active antiretroviral therapy-treated patients"</p><p>http://www.retrovirology.com/content/4/1/60</p><p>Retrovirology 2007;4():60-60.</p><p>Published online 29 Aug 2007</p><p>PMCID:PMC2048509.</p><p></p>vated in four experiments (nos. 1, 2, 3, and 4) or directly polyclonaly activated and cultured with L-731,988 in two other assays (nos. 3 and 4). . latently infected resting CD4T cells were directly polyclonaly activated or preincubated 2 days before polyclonal activation in two experiments (nos. 3 and 4)

Unintegrated HIV-1 provides an inducible and functional reservoir in untreated and highly active antiretroviral therapy-treated patients-3

<p><b>Copyright information:</b></p><p>Taken from "Unintegrated HIV-1 provides an inducible and functional reservoir in untreated and highly active antiretroviral therapy-treated patients"</p><p>http://www.retrovirology.com/content/4/1/60</p><p>Retrovirology 2007;4():60-60.</p><p>Published online 29 Aug 2007</p><p>PMCID:PMC2048509.</p><p></p>umerated at the end of culture. The median values are shown as black bars

Unintegrated HIV-1 provides an inducible and functional reservoir in untreated and highly active antiretroviral therapy-treated patients-4

<p><b>Copyright information:</b></p><p>Taken from "Unintegrated HIV-1 provides an inducible and functional reservoir in untreated and highly active antiretroviral therapy-treated patients"</p><p>http://www.retrovirology.com/content/4/1/60</p><p>Retrovirology 2007;4():60-60.</p><p>Published online 29 Aug 2007</p><p>PMCID:PMC2048509.</p><p></p>re preincubated one or two days before their polyclonal activation. A gate was set on the forward-scatter vs side-scatter histogram. As shown on different histograms, gate corresponded to CD69CD4T lymphocytes. The analysis of the 7AAD level expression demonstrated that activated CD4T lymphocytes were viable cells

Unintegrated HIV-1 provides an inducible and functional reservoir in untreated and highly active antiretroviral therapy-treated patients-6

<p><b>Copyright information:</b></p><p>Taken from "Unintegrated HIV-1 provides an inducible and functional reservoir in untreated and highly active antiretroviral therapy-treated patients"</p><p>http://www.retrovirology.com/content/4/1/60</p><p>Retrovirology 2007;4():60-60.</p><p>Published online 29 Aug 2007</p><p>PMCID:PMC2048509.</p><p></p>HIV-1 integrase inhibitor L-731,988 at the final concentration of 40 μM. . To assess the correlation between the unintegrated HIV-1 DNA decay and the decline of rescuable viral production, infected resting CD4T cells were preincubated 1 or 2 days before polyclonal stimulation. In both cases, in order to prevent infection of others cells by -synthesized HIV-1, 1 μg/ml of the viral entry inhibitor T20 was also added in culture medium

Unintegrated HIV-1 provides an inducible and functional reservoir in untreated and highly active antiretroviral therapy-treated patients-2

<p><b>Copyright information:</b></p><p>Taken from "Unintegrated HIV-1 provides an inducible and functional reservoir in untreated and highly active antiretroviral therapy-treated patients"</p><p>http://www.retrovirology.com/content/4/1/60</p><p>Retrovirology 2007;4():60-60.</p><p>Published online 29 Aug 2007</p><p>PMCID:PMC2048509.</p><p></p>ase inhibitor L-731,988. The median values are shown as black bars. Comparison of results was done by the Wilcoxon signed-rank test

Unintegrated HIV-1 provides an inducible and functional reservoir in untreated and highly active antiretroviral therapy-treated patients-0

<p><b>Copyright information:</b></p><p>Taken from "Unintegrated HIV-1 provides an inducible and functional reservoir in untreated and highly active antiretroviral therapy-treated patients"</p><p>http://www.retrovirology.com/content/4/1/60</p><p>Retrovirology 2007;4():60-60.</p><p>Published online 29 Aug 2007</p><p>PMCID:PMC2048509.</p><p></p>HIV-1 integrase inhibitor L-731,988 at the final concentration of 40 μM. . To assess the correlation between the unintegrated HIV-1 DNA decay and the decline of rescuable viral production, infected resting CD4T cells were preincubated 1 or 2 days before polyclonal stimulation. In both cases, in order to prevent infection of others cells by -synthesized HIV-1, 1 μg/ml of the viral entry inhibitor T20 was also added in culture medium

Comparative distribution of patient’s demographic, clinical and immunological characteristics in the derivation and validation sets.

<p>The main characteristics of the patients are listed here for the time point of enrollment during PHI (M0). For each parameter (except gender), the median values and the range are indicated. Plasma IP-10 concentrations were measured by ELISA at M0. For the derivation set, data are shown for those 45 patients out of 46, whose IP-10 was quantified by ELISA. The validation set comprised 88 patients. There was no significant difference between the two sets for any parameter (p>0.11). W: women, M: men, N: number of patients in each set.</p

Cytokines predictive of immunological set-point levels. (A–E)

<p>Cytokine concentrations in plasma at M0 have been plotted against CD4⁺ T cell counts and T cell activation (CD3⁺CD8⁺CD38⁺HLA-DR⁺) at M6. Six patients, including 4 who were treated at M6, were excluded from the analysis at M6. T cell activation levels were available for 19 patients at M6 (4 SP, 7 SP, 8 RP). The correlations were thus analyzed in 40 patients regarding CD4⁺ T cell counts and viral load and for 19 patients regarding T cell activation. (<b>A</b>) IP-10 levels at M0 plotted against T CD4⁺ counts at M6. (<b>B</b>) IP-10 levels at M0 plotted against T cell activation at M6. (<b>C</b>) IL-18 levels at M0 plotted against T cell activation at M6. (<b>D)</b> TGF-β1 concentrations at M0 plotted against T cell activation at M6. The red line indicates that both the Spearman correlation and the linear regression analysis were significant. <b>(E)</b> Regression analysis for evaluation of the capacity of CD4⁺ T cell counts, VL and cytokines at M0 to predict rapid disease progression. Values obtained for both the derivation set (Luminex and ELISA) and the validation set are shown. Median values of CD4⁺ T cell counts, VL and cytokine levels were used: VL > = 5 log; CD4<570 cells (derivation set); CD4<546 cells (validation set); IP-10> = 869 pg/ml (derivation set, Luminex); IP-10> = 247 pg/ml (derivation set, ELISA); IP-10> = 232 pg/ml (validation set, ELISA).</p