Methodological Characterization of Studies on Discontinuation of PCP prophylaxis.

<p>NR = nor reported for subpopulation of interest.</p><p>CDC = Centre for Disease Control Definition of PCP.</p

Phosphorylation of STAT3 within Th17 cells in response to IL-23 is inhibited by <i>in vitro</i> and <i>in vivo</i> HIV infection and is not restored by HAART.

<p>Blood-derived Th17 cells from healthy donors were infected with HIV for 24 hours. Input virus was washed out, and cells were stimulated with IL-23 or IL-6 for 15 minutes. <b>(A)</b> Representative histograms showing STAT3 phosphorylation in response to IL-23 or IL-6 in HIV-infected and uninfected Th17 cells. <b>(B)</b> Summary of frequency of Th17 cells responding to IL-23 or IL-6 by phosphorylation of STAT3 (%pSTAT3+). * p = 0.001, n = 5. <b>(C)</b> Representative histograms demonstrating STAT3 phosphorylation following IL-23 (top) and IL-6 (bottom) stimulation in Th17 cells isolated from patients and healthy controls. <b>(D)</b> Summary of IL-23 induced pSTAT3 responses in circulating Th17 cells from HIV seronegative, HIV-infected untreated and HIV-infected HAART donors (* p < 0.001, n = 7) and IL-6-induced pSTAT3 responses in Th17 cells isolated from HIV infected donors.</p

Incidence of PCP in HIV-infected Individuals in Various Situations.

<p>Incidence of PCP in HIV-infected Individuals in Various Situations.</p

Incidence of PCP in HIV-infected Individuals on Antiretroviral Therapy who Discontinue Prophylaxis with CD4+ Count <200 cells/µL with Suppressed Viral Load.

<p>Incidence of PCP in HIV-infected Individuals on Antiretroviral Therapy who Discontinue Prophylaxis with CD4+ Count <200 cells/µL with Suppressed Viral Load.</p

HIV infection does not downregulate IL-23R expression.

<p>Circulating Th17 cells were isolated from HIV-seronegative or untreated HIV-infected individuals and expression of IL-23R was assessed by flow cytometry. <b>(A)</b> Representative histograms demonstrating IL-23R expression on circulating Th17 cells isolated from HIV-seronegative controls, HIV-infected untreated, HIV-infected HAART treated individuals and the matched IL-23R isotype control. <b>(B)</b> Summary of % cells expressing IL-23R on circulating Th17 cells from HIV seronegative and untreated HIV-infected patients. <b>(C)</b> Western blot demonstrating expression of IL-12Rβ1 on blood Th17 cell lysates from HIV-seronegative and HIV infected, untreated donors. Figure is representative of 3 out of 6 donors tested.</p

HIV reduces IL-17 secretion and intracellular expression in blood-derived and <i>in vitro</i>-generated Th17 cells.

<p>Blood-derived and <i>in vitro</i> generated Th17 cells were infected with HIV for 24 hours. <b>(A)</b> Th17 cells were cultured for 3 days with anti-CD3 and anti-CD28 mAbs. Supernatants were harvested and assayed for secreted IL-17 by ELISA; * p < 0.001, n = 9; ** p = 0.045, n = 9. Data shown are mean ± SEM. <b>(B)</b> Representative histograms showing intracellular expression of IL-17 in Th17 cells stimulated for 6 hours with PMA and onomycin in the presence of brefeldin A. (<b>C)</b> Summary of the proportion of blood-derived and <i>in vitro</i> generated Th17 cells expressing IL-17 following PMA and ionomycin stimulation is shown with mean frequency indicated; + p = 0.026, n = 9, ++ p = 0.012, n = 5.</p

Incidence Rates of PCP with Discontinuation of PCP prophylaxis with CD4 count ≤200 cells/µL and Fully Suppressed Viral Load (VL).

<p>NR = not reported for subpopulation of interest.</p><p>*Based on combined data for CD4≤100 and 101–200 cells.</p

<i>In vitro</i> HIV infection does not affect RORC, RNA levels in blood-derived Th17 cells.

<p>Blood-derived Th17 cells were infected with HIV for 24 hours. Input virus was washed out and cells were stimulated with anti-CD3 and anti-CD28 mAbs for 3 days. mRNA was isolated and quantified by real-time qPCR for RORC genes. Relative mRNA levels were calculated using the ΔΔCt method, normalized to 18S rRNA. Results are expressed as fold change relative to unstimulated, uninfected cells. n = 9.</p

Clinical characteristics of HIV-infected study subjects.

<p>Clinical characteristics of HIV-infected study subjects.</p

Results of key virologic endpoints from identified trials in ARV-naive patients¹.

<p>Results of key virologic endpoints from identified trials in ARV-naive patients<a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0148231#t002fn002" target="_blank">¹</a>.</p