Prediction of the HLA restriction of Gag p24_276–285 MYSPVSILDI (MI10) and p24_277–285 YSPVSILDI (YI9) using <i>in silico</i> methods.

<p>HLA restriction prediction against two reactive Gag peptides, Gag p24_276–285 MYSPVSILDI (MI10) and p24_277–285 YSPVSILDI (YI9) was performed by the docking simulation model, and the binding motif HLArestrictor 1.2. The U_dock rank by the docking simulation model against MI10 and YI9 was analyzed in the original 15-mer peptides of Gag p24_271–285 NKIVRMYSPVSILDI (NI15) and p24_276–290 MYSPVSILDIRQGPK (MK15). SB: Strong Binder, WB: Weak Binder.</p

Example of epitope prediction using the novel <i>in silico</i> docking simulation model.

<p>U_dock scores of the N-terminal (Row N1–N8) and C-terminal (Column C1–C8) was calculated and their sum was scored as the U_dock score (kcal/mol) of each 8 to 11-mer peptide's. The lower score indicated stronger binding between the peptide and HLA. In this example, Gag p24_263–272 KRWIILGLNK (KK10), well-known as one of the best-defined epitopes, scored −137.11 kcal/mol against HLA-B*27:05 and was the lowest (ranked as the 1st) among 26 variants in 15-mer peptide of Gag p24_258–272 VGEIYKRWIILGLNK.</p

Evaluation of best-defined epitope prediction among docking simulation model, HLArestrictor, and positives in dual models.

<p>Evaluation of best-defined epitope prediction among each model and positives in dual models were statistically evaluated, according to their sensitivity, specificity, positive prediction value (PPV) and negative prediction value (NPV) by maximum Fisher's exact test. DSM: Docking simulation model.</p

<i>In silico</i> epitope prediction for ELISpot responders carrying HLA alleles currently unknown to restrict CRF01_AE epitopes.

<p>We found 27 CRF01_AE specific CTL responses induced in patients carrying HLA alleles previously unknown to restrict CRF01_AE epitopes. Prediction of the optimal epitope within the peptide and its restricting HLA allele was performed using the <i>in silico</i> epitope prediction model HLArestrictor. In total, 19 epitope-HLA combinations were detected with binder levels defined as SB (Strong Binder), WB (Weak Binder), or CB (Combined Binder). NA: Not available, and BL: Binder level.</p

Cytotoxicity assay with T cells Demonstration of a novel epitope-HLA association by ⁵¹Cr release assay.

<p>Specific lysis of Gag peptide p24_122–130 PPIPVGDIY (PY9) pulsed allogeneic target cells by effector CTLs from a HLA-B*40:01+ donor was assessed in a chromium release assay. The <i>Y</i> axis shows percentage specific lysis at an E∶T ratio of 20∶1 with the lysis (%) of unpulsed target cells subtracted. Effector cells were derived from patient 1509. HLA-B*40:01 matched cells pulsed with PY9 were also recognized by patient 326 (data not shown). HLA alleles shared by target cells and effector cells are shown; control indicates HLA-unmatched cells.</p

Sex differences in CD4+ T cell count, CD4% and viral load, amongst 2,101 ART-naïve South African children.

<p>A. Absolute CD4 counts changes with age. B. CD4% changes with age. C. Viral load changes with age. In each panel, the solid lines are Loess-smoothed regression lines for female children and the dotted lines are Loess-smoothed regression lines for male children. A multivariable linear regression model, with both sex and age as covariates, shows significantly lower absolute CD4 counts in males (p = 0.005); significantly lower CD4% in males (p = 3.7x10^-7); and no significant difference in viral load between the sexes.</p

Multivariate analysis of sex differences in CD4+ T cell recovery after initiating ART.

<p>^a HR: Hazard ratio</p><p>^b 95% confidential interval range</p><p>^c aHR: adjusted hazard ratio</p><p>Multivariate analysis of sex differences in CD4+ T cell recovery after initiating ART.</p

Absolute CD4 count, CD4% and viral load in HIV-infected children and HIV-uninfected neonates.

<p>^<b>a</b> Mann Whitney test</p><p><u>HIV-Infected Children, n = 2,101</u>.</p

Proportion of HIV-infected children who were female in the subgroups analyzed within the Kimberley cohort.

<p>The proportion of female children in whom ART was initiated at CD4 counts higher than the CD4 thresholds compared to those in whom ART was initiated at CD4 counts lower than the CD4 thresholds differed significantly (p<0.001).</p

Indications for ART Initiation in 222 children whose CD4 counts were above CD4 treatment thresholds.

<p>^a Not within the guidelines for ART initiation in children</p><p>Indications for ART Initiation in 222 children whose CD4 counts were above CD4 treatment thresholds.</p