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.
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).