Staging of immuno-virological dynamics during acute HIV infection in a Belgian prospective cohort study

Abstract

Background: The events during acute HIV infection (AHI) set the stage for the subsequent course of the disease. Early initiation of antiretroviral therapy (ART) has been associated with favorable immunovirological outcomes, yet the precise impact of ART timing during AHI remains unclear, particularly on lymphoid tissues.

Materials and methods: The ACS cohort is a prospective cohort study in Belgium, collecting longitudinal clinical data and human bodily material (HBM) from people diagnosed and treated during AHI. The aim of the cohort is to study the impact of ART initiation during AHI on HIV reservoir and immune dysfunction in peripheral blood and anatomical sanctuary sites, as well as its effect on the gut microbiome. The cohort consists of two HBM sampling trajectories: one limited (blood, stool and leukapheresis) and a more extensive one (blood, stool, leukapheresis, colonoscopy, inguinal lymph node excision and lumbar puncture). Here we describe the baseline characteristics, immunovirological outcomes, safety and tolerability of HBM sampling.

Results: Between March 2016 and April 2024, 47 participants were enrolled, predominantly men who have sex with men (MSM), with a median age of 36 years [IQR 30-43.5]. Almost 90 % of participants initiated ART within 72 h after study inclusion, irrespective of HBM sampling trajectory. The timing of ART initiation according to the Fiebig stage did not significantly impact immune recovery (CD4/CD8 ratio ≥1) or the time to viral suppression. Approximately 40 % of participants opted for the extensive HBM sampling trajectory during AHI. However, the participation rate for the extensive trajectory decreased by nearly half at the longitudinal follow-up timepoint. In general, study-related procedures were safe and well-tolerated, with limited procedure-related adverse events (AEs). Inguinal lymph node excision was associated with the highest AE rate, in line with previous reports.

Conclusions: Our findings reaffirm the beneficial effect of ART initiation during AHI on long term immunovirological outcomes, regardless of Fiebig stage at treatment initiation. Additionally, we demonstrate that the collection of HBM during and longitudinally after AHI is safe and feasible, without compromising time to ART initiation. Cohorts that integrate comprehensive clinical data with high-quality HBM samples are essential to longitudinally study the impact of early ART on reservoir dynamics and immune responses across various anatomical sites after AHI.

Keywords: Acute HIV infection; Antiretroviral therapy; HIV-1; Human bodily material sampling; Immunovirological outcomes.

Fig. 1

Schematic overview of the study design of the Belgian ACS cohort. Image created with BioRender.com. ART: antiretroviral therapy.

Fig. 2

Immunovirological outcomes in the Belgian ACS cohort during and longitudinally after acute HIV infection. (A–C) Comparison of CD4 T cell counts (A), CD4/CD8 ratio (B) and plasma HIV viral load (log10 copies/mL) (C) during acute HIV infection (T0) between participants diagnosed during Fiebig stages II-III and Fiebig stages IV-VI. P-values were calculated using Wilcoxon rank-sum test. (D–F) Longitudinal course of CD4 T cell counts (D), CD4/CD8 ratio (E) and plasma HIV viral load (F). Solid lines represent median values for Fiebig stages II-III and Fiebig stages IV-VI, shaded areas represent interquartile ranges, dotted lines represent individual participants.

Fig. 3

Survival analysis of immunovirological outcomes after ART initiation during acute HIV infection. (A) Kaplan-Meier survival curve representing the time since ART initiation (days) and proportion of participants with a CD4/CD8 ratio ≥1, stratified by Fiebig stage (Fiebig stage II-III vs Fiebig stage IV-VI). Nine participants with a CD4/CD8 T-cell ratio ≥1 at baseline were excluded from this analysis. (B) Kaplan-Meier survival curve representing the time since ART initiation (days) and proportion of participants with plasma HIV viral load <20 copies/mL, stratified by Fiebig stage (Fiebig stage II-III vs Fiebig stage IV-VI). ART: antiretroviral therapy, VL: viral load.

Fig. 4

Participation rate in invasive HBM sampling procedures in the ACS cohort. Bar chart representing the number of participants and percentage of total participants per sampling procedure at T0, UD, UD+1 and UD+5. CSF: cerebrospinal fluid, HBM: human bodily sampling.