Fig 1.
Longitudinal viral loads for 39 RV217 participants.
Day 0 corresponds to the first HIV-1 positive RNA test, also referred to as diagnosis. The last negative HIV-1 RNA test occurred a median of 4 days prior to diagnosis for these participants. Panel B zooms in on the viral loads from diagnosis to peak. Participants with single founders are represented in grey, those with multiple founders in pink.
Fig 2.
HIV-1 diversification kinetics over the first six months of infection for 39 RV217 participants.
The cumulative number of polymorphic sites across all env sequences sampled for each participant are shown at three time points. Day 0 corresponds to the first HIV-1 positive RNA test. Participants with single founders are represented in grey, those with multiple founders in pink.
Fig 3.
HIV-1 infection occurred a median of six days before HIV-1 diagnosis for individuals infected with single HIV-1 founder variants.
The posterior medians (circle) and 95% highest posterior density interval for the best fitting model using BEAST are represented in grey for participants with single founder viruses (panel A) and in pink for those with multiple founders (panel B). The shaded blue area corresponds to the interval between the last negative and first positive HIV-1 RNA test (or diagnosis date); the time scales differ between infections with single and multiple founders. Two pregnancies were identified in acute infection: these participants had infection estimates close to their diagnosis date (1.87 and -1.35 days for 20368 and 30190, respectively).
Table 1.
Estimated dates of HIV-1 infection for participants with single or multiple HIV-1 founders.
Median and inter-quartile range are given for the different methods investigated for all individuals (excluding those without informative temporal signal from the phylogenetic analyses) and separately for participants with single or multiple founders. The first visit from participant 30812 was excluded from Poisson-Fitter estimates (the sequence set corresponded to multiple founders and failed to go through the requirement for homogenous sequences after using the gap procedure). For hiv-founder-id, estimates were based on a subset of 28 participants, including 7 with multi-founder infections.
Fig 4.
Estimated infection dates based on viral growth rates.
The date when viral loads corresponded to 1 copy per mL of blood was calculated using three methods: highest expansion (rmax), individual linear models (lm) and linear mixed-effects model based on data from all subjects (rg). Panel A compares the estimates in two non-human primate (NHP) cohorts with viral load data provided by Drs. Barouch (dataset 1) and Roederer (dataset 2). Panel B shows the estimates calculated with rmax for RV217 participants infected with single or multiple HIV-1 founder viruses. Day 0 corresponds to the day of challenge for the NHP in Panel A and to the day of the first positive HIV-1 RNA test for RV217 participants (Panel B).
Fig 5.
Estimates of the date of infection using three methods for 22 participants (10066 to 30190).
The figures show for each individual the viral load measurements in the viral upslope (in blue), the self-reported possible transmission event (dotted black line) and the estimated dates based on molecular dating (in green), Poisson-Fitter (in plum) and viral load growth rates (in yellow). The shaded blue area corresponds to the interval between the last negative and first positive HIV-1 RNA test (or diagnosis date). The bar on top of each graph shows the participant id number along with additional information about whether they were categorized as infections with single or multiple founders, whether their sequences showed insufficient signal for phylogenetic analyses (Lack of Signal, LOS) and whether they became pregnant during this time frame, as well as their set point viral load (SPVL in log10 copies/mL).
Fig 6.
Estimates of the date of infection using three methods for 20 participants (30507 to 40577).
The figures show for each individual the viral load measurements in the viral upslope (in blue), the self-reported possible transmission event (dotted black line) and the estimated dates based on molecular dating (in green), Poisson-Fitter (in plum) and viral load growth rates (in yellow). The shaded blue area corresponds to the interval between the last negative and first positive HIV-1 RNA test (or diagnosis date). The bar on top of each graph shows the participant id number along with additional information about whether they were categorized as infections with single or multiple founders, whether their sequences showed insufficient signal for phylogenetic analyses (Lack of Signal, LOS) and whether they became pregnant during this time frame, as well as their set point viral load (SPVL in log10 copies/mL).