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A Cause of HIV Persistence

February 12, 2014

A Cause of HIV Persistence

  1. Richard T. Ellison III, MD

Low antiretroviral drug concentrations in lymphatic tissue appear to contribute to viral persistence.

  1. Richard T. Ellison III, MD

Although antiretroviral therapy (ART) has vastly improved quality of life and decreased mortality for HIV-infected individuals, patients often continue to have low levels of CD4 cells in lymphatic tissue.

Noting that drug-distribution studies in animal models of AIDS had shown antiretroviral (ARV) drug concentrations to differ between tissues and peripheral blood, investigators started 12 HIV-infected individuals on ART (tenofovir and FTC plus efavirenz, ritonavir-boosted atazanavir, or darunavir) and followed them for 6 months, taking samples of peripheral blood as well as lymph node, ileal, and rectal tissue. Before the study, 10 of the individuals had been ART naive, and the other 2 had been off ART for >1 year.

All participants achieved expected ARV concentrations in plasma and peripheral blood mononuclear cells (PBMCs). However, the concentrations of all five ARVs were significantly lower in lymphatic tissue — and particularly so in lymph node mononuclear cells, where the intracellular levels of tenofovir, FTC, atazanavir, darunavir, and efavirenz were, respectively, 80%, 66%, 100%, 99%, and 94% lower than in PBMCs. In addition, although all participants showed the expected reduction in plasma viral load, in situ hybridization studies revealed evidence of ongoing viral replication in lymphatic tissue. The intracellular concentrations of tenofovir and of FTC were significantly negatively correlated with the size of the HIV virion pool in such tissue.

Comment

These findings provide a new perspective on HIV persistence and suggest that the development of new antiretroviral formulations with enhanced lymphatic tissue penetration could be of great benefit in reducing the adverse effects of ongoing viral replication.

  • Disclosures for Richard T. Ellison III, MD at time of publication Grant / research support NIH-NIAID

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