The Lymph Node Reservoir: Physiology, HIV Infection, and Antiretroviral Therapy

Clin Pharmacol Ther. 2021 Apr;109(4):918-927. doi: 10.1002/cpt.2186. Epub 2021 Feb 28.


Despite advances in treatment, finding a cure for HIV remains a top priority. Chronic HIV infection is associated with increased risk of comorbidities, such as diabetes and cardiovascular disease. Additionally, people living with HIV must remain adherent to daily antiretroviral therapy, because lapses in medication adherence can lead to viral rebound and disease progression. Viral recrudescence occurs from cellular reservoirs in lymphoid tissues. In particular, lymph nodes are central to the pathology of HIV due to their unique architecture and compartmentalization of immune cells. Understanding how antiretrovirals (ARVs) penetrate lymph nodes may explain why these tissues are maintained as HIV reservoirs, and how they contribute to viral rebound upon treatment interruption. In this report, we review (i) the physiology of the lymph nodes and their function as part of the immune and lymphatic systems, (ii) the pathogenesis and outcomes of HIV infection in lymph nodes, and (iii) ARV concentrations and distribution in lymph nodes, and the relationship between ARVs and HIV in this important reservoir.

Publication types

  • Research Support, N.I.H., Extramural
  • Review

MeSH terms

  • Anti-Retroviral Agents / pharmacokinetics
  • Anti-Retroviral Agents / pharmacology*
  • CD4-Positive T-Lymphocytes / immunology
  • HIV Infections / drug therapy*
  • HIV Infections / physiopathology*
  • Humans
  • Immunity / physiology*
  • Lymph Nodes / drug effects
  • Lymph Nodes / physiology
  • Lymphatic System / physiology*
  • Viral Load


  • Anti-Retroviral Agents