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.
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.
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.
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.
From the *Department of Infectious Diseases, the Sahlgrenska Academy at University of Gothenburg, Gothenburg, Sweden; †AIDS Reference Laboratory, Ghent University, Ghent, Belgium; ‡Department of Infectious Diseases, Laboratory of Clinical Pharmacology and Pharmacogenetics, University of Torino, Torino, Italy; §Pharmacology Research Laboratories, University of Liverpool, Liverpool, United Kingdom; ‖NIHR Biomedical Research Centre, Royal Liverpool and Broadgreen University Hospitals Trust, Liverpool, United Kingdom; ¶Division of Biological Chemistry, Biocentre, Innsbruck Medical University, Innsbruck, Austria; and #Department of Virology, The Sahlgrenska Academy at University of Gothenburg, Gothenburg, Sweden.
Received for publication April 10, 2010; accepted July 27, 2010.
Supported by grants from the Sahlgrenska Academy at the University of Gothenburg (ALFGBG-11067), the Research Foundation of Swedish Physicians Against AIDS, Roche, Pfizer, and the Swedish Research Council (Project 2007-7092).
Part of the data were presented at 17th Conference on Retroviruses and Opportunistic Infections (CROI), February 16-19, 2010, San Francisco, CA.
Correspondence to: Magnus Gisslén, MD, PhD, Department of Infectious Diseases, Sahlgrenska University Hospital, 416 85 Gothenburg, Sweden (e-mail: firstname.lastname@example.org).