Neighbour joining trees and Highlighter plots of longitudinal HIV-1 gag diversity from recently infected individuals.

<p>(A) Neighbour-joining phylogenetic tree of longitudinal (from 14 days to 1 year post infection) <i>gag</i> sequences from 22 recently infected HIV-1 participants and consensus subtype C reference sequence from the HIV database (<a href="http://www.hiv.lanl.gov" target="_blank">www.hiv.lanl.gov</a>). Gag sequences from the earliest time point are shown in red circles and in blue circles at 1 year post infection. (*) denotes samples sequenced later than 14 days post infection (AS3–0513, AS2–1037, AS2–0802, AS2–0945 and AS1–0876 were sequenced at 28, 34, 35, 46 and 101 days post-infection respectively). (B) Participant AS3_0513 with a highly homogeneous <i>gag</i> sequence population at screening (∼28 days post infection) displaying limited structure on a tree (left) and little or no nucleotide changes from the intrapatient consensus at 28 days post infection. (C) Participant AS3_0767 infected with four closely related <i>gag</i> populations based on the clustering of sequences. Heterogeneous, multiple variant <i>gag</i> sequences population at 14 days post infection visually represented by a phylogenetic tree (left) with extensive branching topology and Highlighter plots (right) with diverse pattern of nucleotide base mutations compared to consensus. Nucleotide polymorphisms are indicated by a colored tic mark (thymine in red, adenine in green, cytosine in blue and guanine in orange) and deletions are shown by gray tics in the Highlighter plots. (★) denotes the consensus sequence obtained from the earliest time point sequences.</p

Percentage distribution of consensus and variant Gag sequence patterns in individuals over one year of HIV-1 infection.

<p>(A) Percentage of consensus, variant and known CTL variants within host specific epitopes from HLA class I alleles at one year post infection. Distribution of consensus, variant and percentage of variants as CTL variants within host-specific HLA restricted Gag epitopes in individuals possessing the selecting HLA-A (B), HLA-B (C) and HLA-C (D) allele and those individuals who do not possess the selecting HLA allele over one year of infection. (E) Overall distribution of adapted and non-adapted HLA-associated escape mutations within individuals that select and do not select for Gag polymorphisms by one year post infection. Distribution of adapted (F) and non-adapted (G) mutations expressing HLA-A, HLA-B and HLA-C alleles that select and do not select for Gag polymorphisms one year post infection.</p

Summary of reversion of HLA associated mutations following transmission in the presence or absence of the selecting HLA type.

<p><i>a</i>"None" indicates no known HLA-association of mutation</p><p><i>b</i>(+): presence of HLA-association, (−): absence of previously identified HLA association</p><p>Bold restricting HLA indicates the HLA which is positively associted with the non-adapted mutation at one-year post infection</p><p>Summary of reversion of HLA associated mutations following transmission in the presence or absence of the selecting HLA type.</p

Summary of reversion within CTL epitopes following transmission in the presence or absence of the selecting HLA type.

<p><i>a</i>Bold residues denotes known CTL escape mutation</p><p><i>b</i>(+): presence of HLA-association, (−): absence of previously identified HLA association</p><p>Underlining denotes the CTL epitope in the peptide sequence</p><p>Summary of reversion within CTL epitopes following transmission in the presence or absence of the selecting HLA type.</p

Demographic and clinical characteristics of the study participants.

<p>*CD4+ cell counts were not performed at screening; the values given are for 2–4 weeks post screening</p><p>♦Viral loads were performed at screening</p><p>† CDC criteria followed for the interpretation of Western Blot results</p><p>Demographic and clinical characteristics of the study participants.</p

Multiple variant transmission and intrapatient diversity results in higher viral load set point.

<p>(A) Association of single versus multivariant transmission sequences versus viral load set point in individuals sequenced at the earliest time point (Student’s T test). (B) Significantly higher intrapatient diversity in individuals infected with multiple variants (Student’s T test). (C) Significantly higher intrapatient diversity within <i>gag</i> over one year of infection (Paired T test). (D) Intrapatient diversity of HIV-1 Gag at 14 days post infection correlation with viral load set point. Significant correlations of intrapatient diversity at 1 year versus viral load set point (E) and viral load at one year (F). (*) denotes statistical significant difference.</p