Impact of early cART on HIV blood and semen compartments at the time of primary infection

Abstract

Background: HIV-infected cells in semen facilitate viral transmission. We studied the establishment of HIV reservoirs in semen and blood during PHI, along with systemic immune activation and the impact of early cART.

Methods: Patients in the ANRS-147-OPTIPRIM trial received two years of early cART. Nineteen patients of the trial were analyzed, out of which 8 had acute PHI (WB ≤1 Ab). We quantified total cell-associated (ca) HIV-DNA in blood and semen and HIV-RNA in blood and semen plasma samples, collected during PHI and at 24 months of treatment.

Results: At enrollment, HIV-RNA load was higher in blood than in semen (median 5.66 vs 4.22 log10 cp/mL, p<0.0001). Semen HIV-RNA load correlated strongly with blood HIV-RNA load (r = 0.81, p = 0.02, the CD4 cell count (r = -0.98, p<0.0001), and the CD4/CD8 ratio (r = -0.85, p<0.01) in acute infection but not in later stages of PHI. Median blood and seminal cellular HIV-DNA levels were 3.59 and 0.31 log10cp/106 cells, respectively. HIV-DNA load peaked in semen later than in blood and then correlated with blood IP10 level (r = 0.62, p = 0.04). HIV-RNA was undetectable in blood and semen after two years of effective cART. Semen HIV-DNA load declined similarly, except in one patient who had persistently high IP-10 and IL-6 levels and used recreational drugs.

Conclusions: HIV reservoir cells are found in semen during PHI, with gradual compartmentalization. Its size was linked to the plasma IP-10 level. Early treatment purges both the virus and infected cells, reducing the high risk of transmission during PHI.

Clinical trials registration: NCT01033760.

Conflict of interest statement

Competing Interests: AC reports grants from Merck and personal fees from Gilead, ViiV and Janssen, unrelated to the submitted work. V-AF received conference fees from ViiV and financial support for international conference participation from Janssen, unrelated to the submitted work. CG declares to have received conference fees and other financial support from Janssen, Gilead, ViiV and MSD, unrelated to the submitted work. This does not alter our adherence to PLOS ONE policies on sharing data and materials CR received conference fees. All the other authors declare that they have no conflict of interest.

Figures

Fig 1. HIV-RNA and HIV-DNA load and HIV-RNA/HIV-DNA ratio during PHI before cART initiation, in blood and semen, in patients with acute infection (n = 8, black dots) and recent infection (n = 11, triangles).

Fig 2

(a) Correlogram of baseline virological and immunological markers for 19 patients. Heatmaps and pie charts indicate associations between the variables. Red indicates a positive correlation and blue a negative correlation. The intensity and size of the colored part of pie represent the strength of the association. Spearman correlations were assumed for p values <0.05 between virological markers and immunological markers. (b) Circle of correlations of baseline virological and immunological markers with the first two components from Principal Component Analysis (PCA) (65% of the total variance). Blood and semen HIV-RNA and HIV-DNA are designated as follows: bRNA, bDNA, sRNA, sDNA.

Fig 3. Correlations between seminal HIV-RNA and (a) blood HIV-RNA, (b) the CD4 cell count, and (c) the CD4/CD8 ratio, and between IP-10 and (d) blood HIV-RNA (e) seminal HIV-DNA, and (f) blood HIV-DNA, according to primary infection status: Acute infection (black dots), and recent infection (triangles).

Fig 4. Changes in seminal and blood HIV-RNA and HIV-DNA between D0 (cART initiation during PHI) and M24 (2 years of cART).

As shown on the right panel, an increase in seminal HIV-DNA load with stable blood HIV-DNA load occurred in two patients. Horizontal lines are the detection thresholds.