Treatment intensification has no effect on the HIV-1 central nervous system infection in patients on suppressive antiretroviral therapy

J Acquir Immune Defic Syndr. 2010 Dec 15;55(5):590-6. doi: 10.1097/QAI.0b013e3181f5b3d1.


Background: Antiretroviral treatment (ART) significantly reduces cerebrospinal fluid (CSF) HIV-1 RNA levels and residual viremia is less frequently found in CSF than in blood. However, persistent intrathecal immunoactivation is common, even after several years of ART. To investigate whether low-level CSF viremia and residual immunoactivation within the central nervous system (CNS) derive from ongoing local viral replication, we conducted a study of treatment intensification in patients on effective ART.

Methods: Ten patients on ART with plasma HIV RNA <50 copies per milliliter for >18 months were included. Intensification was given for in total 8 weeks: 4 weeks with maraviroc or lopinavir/ritonavir (good CNS penetration), and 4 weeks with enfuvirtide (poor CNS penetration). Lumbar punctures were performed 4 weeks before, at intensification commencement, at switchover after 4 weeks, at the conclusion of, and 4 weeks after the intensification period.

Results: No significant changes in HIV RNA, neopterin, β2-microglobulin, immunoglobulin G index, albumin ratio, and CD4(+) T-cell count were observed, either in CSF or blood, neither before, during, nor after the intensification periods.

Conclusions: ART intensification did not reduce residual CSF HIV RNA levels or intrathecal immunoactivation in patients on ART. These findings do not support an ongoing viral replication in CNS.

Publication types

  • Clinical Trial
  • Randomized Controlled Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Albumins / cerebrospinal fluid
  • Anti-HIV Agents / blood
  • Anti-HIV Agents / cerebrospinal fluid
  • Anti-HIV Agents / therapeutic use*
  • Antiretroviral Therapy, Highly Active
  • CD4 Lymphocyte Count
  • CD4-Positive T-Lymphocytes / virology
  • Central Nervous System Infections / drug therapy*
  • Central Nervous System Infections / virology*
  • Cross-Over Studies
  • Cyclohexanes / therapeutic use
  • Enfuvirtide
  • Female
  • HIV Envelope Protein gp41 / therapeutic use
  • HIV Infections / drug therapy*
  • HIV Infections / virology*
  • HIV-1 / drug effects*
  • HIV-1 / physiology
  • Humans
  • Immunoglobulin G / blood
  • Immunoglobulin G / cerebrospinal fluid
  • Lopinavir / therapeutic use
  • Male
  • Maraviroc
  • Middle Aged
  • Neopterin / blood
  • Neopterin / cerebrospinal fluid
  • Peptide Fragments / therapeutic use
  • Polymerase Chain Reaction
  • RNA, Viral / blood
  • RNA, Viral / cerebrospinal fluid
  • Ritonavir / therapeutic use
  • Triazoles / therapeutic use
  • Viral Load
  • Viremia
  • Virus Replication


  • Albumins
  • Anti-HIV Agents
  • Cyclohexanes
  • HIV Envelope Protein gp41
  • Immunoglobulin G
  • Peptide Fragments
  • RNA, Viral
  • Triazoles
  • Enfuvirtide
  • Lopinavir
  • Neopterin
  • Maraviroc
  • Ritonavir