Viral load dynamics and pre-peak viremia HIV-1 genetic diversity in 6 participants from the RV217 cohort.

<p>a) Plasma viral load (red) and CD4+ T-cell counts (blue) are shown for six volunteers with documented NAT-conversion. Day 0 represents the first date of NAT-positivity. Black-bordered circles depict the time points where HIV-1 sequencing was performed, and asterisks indicate samples obtained during Fiebig stage I/II. The dotted line depicts the lower limit of detection of the plasma viral load assay. b) Highlighter plots depicting the SGS-based analysis. For each SGS sequence, differences from the consensus of the major T/F virus are indicated by colored tic marks: green = A, blue = C, orange = G, red = T, and gray = deletion. c) Using TDS, the low-level presence of minor T/F viruses was detected in 5 participants; the time of first detection and their frequencies are indicated in pie charts (ranges depict measurements in different HIV-1 sub-genomic regions). Sequences of the minor T/F viruses were obtained during AHI either by SGS or by sequence-specific PCR (SSP); highlighter plots show that minor T/F viruses were highly related but distinct from cognate major T/F viruses.</p

Summary of viral dynamics during AHI.

<p>For the 6 participants considered in the current study, we compare the dynamics of pVL, of the frequency of the major T/F lineage, and of viral escape from CTL responses. For the sake of clarity, the curves were aligned based on day of peak viremia. For epitope Gag SM9 in participant 40061, the initial replacement of the major T/F by the minor T/F sequence is indicated separately from the later escape that proceeded through epitope shattering (1 and 2, respectively). For participant 40265, the CTL epitope in Rev has not been mapped.</p

40100 major and minor T/F viruses present distinct phenotypes in in vitro competition assays.

<p>a) The replication capacity of FLIMCs from 40100 major and minor T/F viruses was compared. Lines represent the proportion of infected cells that carried each T/F virus. Colors code for each experiment, which were conducted on PBMCs or the A3R5 cell line, as indicated. b) Ratio of cells infected with minor vs. major T/F virus after 6-day culture in PBMCs in control conditions (black), and in the presence of IFN alpha (blue) or IFN beta (red). c) Ratio of cells infected with minor vs. major T/F virus after 6-day culture in RA-treated PBMCs in the absence (blue, green) or presence (red, orange) of α4β7-blocking mAb Act-1. Data for two different PBMC donor pools, 50+94 and 78+150, are shown. In all the experiments, the initial inoculum was a 1:1 mixture of the two viruses (dotted lines). Whiskers represent interquartile intervals.</p

T/F virus dynamics during AHI in participants with infections established by multiple T/F viruses.

<p>a) The frequency of major and minor T/F lineages, and b) their contribution to the total viral load (gray area) are shown. For clarity, different variants within a T/F lineage were combined.</p

Clinical characteristics of 6 participants from the acute HIV-1 infection cohort RV217.

<p>Clinical characteristics of 6 participants from the acute HIV-1 infection cohort RV217.</p

Early and frequent sampling during acute HIV-1 infection (AHI) in 6 participants from RV217.

<p>Early and frequent sampling during acute HIV-1 infection (AHI) in 6 participants from RV217.</p

Socio-demographic and risk characteristics of 6 participants from the acute HIV-1 infection cohort RV217.

<p>Socio-demographic and risk characteristics of 6 participants from the acute HIV-1 infection cohort RV217.</p

Estimated escape rates from early CTL responses during acute HIV infection.

<p>Estimated escape rates from early CTL responses during acute HIV infection.</p