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

PLoS One. 2017 Jul 14;12(7):e0180191. doi: 10.1371/journal.pone.0180191. eCollection 2017.

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.

Publication types

  • Clinical Trial, Phase III
  • Randomized Controlled Trial

MeSH terms

  • Acute Disease
  • Adult
  • Anti-Retroviral Agents / therapeutic use*
  • CD4-CD8 Ratio
  • Enzyme-Linked Immunosorbent Assay
  • HIV Infections / drug therapy*
  • HIV-1 / genetics
  • HIV-1 / isolation & purification
  • Humans
  • Interleukin-6 / analysis
  • Leukocytes, Mononuclear / virology
  • Male
  • Middle Aged
  • Principal Component Analysis
  • RNA, Viral / analysis
  • RNA, Viral / blood*
  • Real-Time Polymerase Chain Reaction
  • Semen / virology*
  • Time Factors
  • Viral Load
  • Young Adult

Substances

  • Anti-Retroviral Agents
  • Interleukin-6
  • RNA, Viral

Associated data

  • ClinicalTrials.gov/NCT01033760

Grants and funding

This work was supported by ANRS. ViiV Healthcare, Gilead, Janssen and MSD acted as co-sponsors through an ANRS contract. MP obtained a fellowship from Sidaction. But no funding bodies had any role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.