Raltegravir treatment intensification does not alter cerebrospinal fluid HIV-1 infection or immunoactivation in subjects on suppressive therapy

J Infect Dis. 2011 Dec 15;204(12):1936-45. doi: 10.1093/infdis/jir667. Epub 2011 Oct 21.

Abstract

Background: Despite suppression of plasma human immunodeficiency virus type 1 (HIV-1) RNA by antiretroviral therapy to levels below clinical assay detection, infection and immune activation may persist within the central nervous system and possibly lead to continued brain injury. We hypothesized that intensifying therapy would decrease cerebrospinal fluid (CSF) infection and immune activation.

Methods: This was a 12-week, randomized, open-label pilot study comparing addition of the integrase inhibitor raltegravir to no treatment augmentation, with an option for rollover to raltegravir. CSF and plasma were analyzed for HIV-1 RNA using a single-copy assay. CSF and blood immune activation was assessed by neopterin concentrations and CD4(+) and CD8(+) T-cell surface antigen expression.

Results: Primary analysis compared 14 intensified (including rollovers) to 9 nonintensified subject experiences. Median HIV-1 RNA levels in all samples were lower in CSF (<.3 copies/mL) than in plasma (<.9 copies/mL; P < .0001), and raltegravir did not reduce HIV-1 RNA, CSF neopterin, or CD4(+) and CD8(+) T-cell activation.

Conclusions: Raltegravir intensification did not reduce intrathecal immunoactivation or alter CSF HIV-1 RNA levels in subjects with baseline viral suppression. With and without raltegravir intensification, HIV RNA levels in CSF were very low in the enrolled subjects. Clinical Trials Registration. NCT00672932.

Publication types

  • Randomized Controlled Trial
  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • ADP-ribosyl Cyclase 1 / metabolism
  • Anti-Retroviral Agents / administration & dosage*
  • Anti-Retroviral Agents / immunology
  • Anti-Retroviral Agents / therapeutic use
  • CD4 Lymphocyte Count
  • CD4-Positive T-Lymphocytes / metabolism
  • CD8-Positive T-Lymphocytes / metabolism
  • Female
  • HIV Infections / blood
  • HIV Infections / cerebrospinal fluid*
  • HIV Infections / drug therapy*
  • HIV Infections / immunology
  • HIV-1*
  • HLA-DR Antigens / metabolism
  • Humans
  • Male
  • Middle Aged
  • Neopterin / blood
  • Neopterin / cerebrospinal fluid
  • Pilot Projects
  • Pyrrolidinones / administration & dosage*
  • Pyrrolidinones / immunology
  • Pyrrolidinones / therapeutic use
  • RNA, Viral / blood
  • RNA, Viral / cerebrospinal fluid*
  • Raltegravir Potassium
  • Receptors, CCR5 / metabolism

Substances

  • Anti-Retroviral Agents
  • HLA-DR Antigens
  • Pyrrolidinones
  • RNA, Viral
  • Receptors, CCR5
  • Raltegravir Potassium
  • Neopterin
  • ADP-ribosyl Cyclase 1

Associated data

  • ClinicalTrials.gov/NCT00672932