Fig. 2: Acute HIV-1 infection alters the human plasma proteome.

Longitudinal protein expression profiles were investigated during hAHI. A comprehensive analysis of 83,643 protein combination values from all three-time points was conducted across 54 study participants, resulting in a total of 1336 profiles. a To identify the optimal clusters representing the longitudinal expression profiles for different groups, the elbow method was employed, leading to identification of six distinct clusters. These clusters were color-coded and plotted, with the x-axis denoting the visit number and the y-axis representing the scaled log-intensity per patient. b Bar plot illustrating the comparison in the number of differentially expressed proteins across visit differences. The height of each bar corresponds to the number of proteins while the bar color varies depending on the visit difference. c Forest plots indicating effect sizes (log2 fold change) and 95% confidence intervals for proteins significantly differentially expressed at 2 weeks and 1 month post estimated date of infection (EDI), relative to pre-infection levels (V1-V0 and V2-V0, respectively), as well as the difference between 2 weeks and 1 month post EDI (V2-V1). Effect sizes are shown in red for the Durban cohort, and blue for the IAVI cohort. Circles and triangles indicate depleted (depl) and neat plasma, respectively. The statistical analysis was conducted using linear mixed-effects models with a random intercept for each patient, treating visit number as a categorical variable. The differential protein expression was assessed using a global ANOVA, with post hoc tests identifying specific visit comparisons (e.g., V0 vs. V1, V0 vs. V2, and V1 vs V2). The Benjamini-Hochberg’s FDR method with a 5% FDR threshold was used to correct for multiple testing, with a fixed p-value cut-off of 0.005. d, e Circos plots visualizing the differentially expressed proteins from different visit differences in a circular layout. The lower ring represents the GO-biological processes associated with the proteins belong to, with each process color-coded for easy identification. The upper rings depict specific classification of these proteins, with proteins secreted in blood shown in orange and the tissue leakage proteins shown in gray. Abbreviations: V0 visit 0 (collected before estimated date of infection); V1 visit 1 (collected 10–14 days post estimated date of infection); V2 visit 2 (collected 15–42 days before estimated date of infection); V1–V0 difference between visit V1 and V0; V2–V0 difference between visit V2 and V0; V2–V1 difference between visit V2 and V1; Log2FC log 2-fold change. Source data are provided as a Source Data file.