Distribution and reduction magnitude of HIV-DNA burden in CD4+ T cell subsets depend on art initiation timing

AIDS. 2018 Apr 24;32(7):921-926. doi: 10.1097/QAD.0000000000001770.

Abstract

Objective: The aim of our study was to analyze the dynamics of HIV-DNA levels in CD4 T-cell subsets in individuals starting successful dolutegravir-based regimens.

Design: Twenty-seven individuals with acute infection (AI, n = 8) or chronic infection (CI, n = 5) and patients in virological success (VS, n = 10) or virological failure (VF, n = 4) on antiretroviral therapy (ART) who initiated a dolutegravir-based regimen were enrolled (NCT02557997).

Methods: CD4 T-cells from baseline and week 48 of successful treatment were sorted into effector memory (TEM), transitional memory (TTM), central memory (TCM) and naïve (TN) cell groups for total HIV-DNA measurements by qPCR. Bayesian methods were used to estimate the posterior probability of a HIV-DNA decrease more than 0.25 log copies/10 cells at week 48.

Results: All patients achieved HIV-RNA suppression at 48 weeks. At baseline and week 48, the highest contributions to the HIV-DNA-infected pool from CD4 T cells were observed in TTM cells in the AI group (62.4 and 60.2%, respectively), but in TCM cells for the CI, VS and VF groups (54.6 and 59.4%, 58.2 and 62.9%, 62.4 and 67.2%), respectively. HIV-DNA burden declined in all subsets after 48 weeks of treatment in the AI (probability (Pr) > 91%), CI (Pr > 52%) and VF (Pr > 52%) groups, but only in TEM cells in the VS group (Pr = 95%).

Conclusion: Our study showed that dolutegravir-based treatment reduced the HIV-DNA cellular burden in individuals from the AI, CI and VF groups, though the reduction levels differed between the patient subgroups. Early treated patients had the highest probability of HIV-DNA reduction. Interestingly, in the aviremic VS group, HIV-DNA reduction was limited to TEM cells.

Publication types

  • Multicenter Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Anti-HIV Agents / administration & dosage*
  • Antiretroviral Therapy, Highly Active / methods
  • CD4-Positive T-Lymphocytes / virology*
  • DNA, Viral / analysis*
  • Female
  • Follow-Up Studies
  • HIV Infections / drug therapy*
  • HIV Infections / virology*
  • Heterocyclic Compounds, 3-Ring / administration & dosage
  • Humans
  • Longitudinal Studies
  • Male
  • Middle Aged
  • Oxazines
  • Piperazines
  • Prospective Studies
  • Pyridones
  • Real-Time Polymerase Chain Reaction
  • T-Lymphocyte Subsets / virology*
  • Time Factors
  • Young Adult

Substances

  • Anti-HIV Agents
  • DNA, Viral
  • Heterocyclic Compounds, 3-Ring
  • Oxazines
  • Piperazines
  • Pyridones
  • dolutegravir

Associated data

  • ClinicalTrials.gov/NCT02557997