Figure 1.
Plasma SIV RNA levels, immunophenotyping, GI biopsy and antibody treatment according to treatment group is shown. D = day post infection. Treatment phase with PMPA/FTC is indicated by the horizontal block-arrow in the right upper hand corner.
Figure 2.
Plasma SIV RNA prior to, following treatment with cMT-807 antibody and over the first week after starting PMPA/FTC.
Data shown are grouped according to treatment group with fit lines for the period pre cMT-807 administration, during cMT-807 administration and during antiretroviral therapy shown as the solid line segments. Note that for the tick marks on the X-axis prior to Day 84 (Week 12) is by 21 day (3 week) increments while after Day 84, the timescale is in 4 day increments.
Table 1.
Summary of viral load dynamics and correlation to CD8 T-cell depletion.
Figure 3.
CD8 T-cell concentrations before, following treatment with cMT-807 antibody and after starting PMPA/FTC.
Results are displayed separately for full depletion, partial depletion and control animals. Time scales differ for each epoch shown and the x-axes are not to scale.
Figure 4.
CD4 T-cell concentrations before, following treatment with cMT-807 antibody and after starting PMPA/FTC.
Results are displayed separately for full depletion, partial depletion and control animals. Time scales differ for each epoch shown and the x-axes are not drawn to scale.
Figure 5.
Correlation between viral rebound rate and death rate δ and % CD8 remaining in peripheral blood (PBMC) and lamina propria lymphocytes (LPL).
Error bars are shown for estimates. Significant negative correlations were found for viral rebound rates and CD8% in PBMC (5A, Spearman r −0.76, p = 0.036,) and CD8% in LPL (5B, Spearman r −0.88, p = 0.0072,) but not for death rate of productively infected cells, δ, and CD8% in either PBMC (5C, Spearman r = −.12, p = 0.79) or LPL (5D, Spearman r = 0.07, p = 0.88). The fit lines shown are simple regression lines and do not directly correspond to the non-parametric, Spearman correlation.
Figure 6.
SIV nef evolution in CD8-depleted animals.
Data from 3 fully depleted animals are shown. A) Sequence alignments of SIVmac251 Nef region demonstrating greatest diversity and evolution during the depletion period (amino acids 141–210). Dashes indicate identity to SIVmac251 inoculum consensus sequence, asterisks indicate premature stop codons, and question marks represent unresolvable sites (due to nucleotide ambiguity). Blue bars highlight positions with statistically significant differences in amino acid distribution between day 84 and day 91 (based on Fisher's Exact, p<0.05). Numbers of sampled clones associated with each predicted protein sequence are listed on right. B) Cumulative behavior of synonymous and nonsynonymous substitutions across nef sequence. Green lines = nonsynonymous mutations, red lines = synonymous substitutions; area between dashed lines represents region displayed in panel A.
Figure 7.
SIV nef evolution in control animals.
Data from 2 non-depleted control animals are shown. A) Sequence alignments of SIVmac251 Nef region demonstrating greatest diversity and evolution in depleted animals (amino acids 141–210). Dashes indicate identity to SIVmac251 inoculum consensus sequence, asterisks indicate premature stop codons, and question marks represent unresolvable sites (due to nucleotide ambiguity). There were no positions with statistically significant differences in amino acid distribution between day 84 and day 91 (based on Fisher's Exact test). Numbers of sampled clones associated with each predicted protein sequence listed on right. B) Cumulative behavior of synonymous and nonsynonymous substitutions across nef sequence. Green lines = nonsynonymous mutations, red lines = synonymous substitutions; area between dashed lines represents region displayed in panel A.