Fig. 4: Alpha-soluble NSF attachment protein, GTP-binding nuclear protein Ran, and Inter-alpha-trypsin inhibitor heavy chain are associated with HIV-1 control.

a Flow chart illustrating the total number of samples used in viral control classification, along with the exclusion criteria. b Longitudinal viral load measures against the number of days post the estimated date of infection (EDI) for all 54 participants. The color-coded boxplots represent the distribution of peak viral load, nadir viral load, days to peak viral load, and days to nadir viral load across the 54 individuals. The center line within the box represents the median, the box bounds the interquartile range, and the whiskers the minimum and maximum values of 1.5× IQR beyond the box. c Dendrogram showcasing complete linkage hierarchical clustering of viral load profiles. Euclidean distances computed from the cubic spline predicted viral load at evenly spread (on transformed scale) time points were used for clustering. The optimal number of clusters was determined using the Silhouette value, and the clustering significance was calculated using multiscale bootstrap resampling. Viral load clusters were based on time 1–12 months (30–364 days). Two distinct groups were classified: No viral control (in green) and sustained viral control (in brown). d Plot representing the cubic spline predicted viral load at evenly spread time points. The differentiation between the two viral control groups occurred at a viral load threshold of 10,000 copies/ml. e Heatmap illustrating associations between viral control and various demographic parameters and ARS symptoms. f 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). 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. Abbreviations: ART antiretroviral treatment, EDI estimated date of infection, ARS acute retroviral syndrome, DC discordant couple, HET heterosexual, MSM men who have sex with men, 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. The asterisk (*) appended to the end of certain protein names indicates proteins detected in neat plasma, while proteins without an asterisk were identified in depleted plasma samples. Source data are provided as a Source Data file.