Raltegravir treatment intensification does not alter cerebrospinal fluid HIV-1 infection or immunoactivation in subjects on suppressive therapy.
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.
Department of Microbiology, Tumor and Cell Biology, Karolinska Institutet and Swedish Institute for Infectious Disease Control, Stockholm, Sweden.
Viktor
V
Dahl
Evelyn
E
Lee
Julia
J
Peterson
Serena S
SS
Spudich
Idris
I
Leppla
Elizabeth
E
Sinclair
Dietmar
D
Fuchs
Sarah
S
Palmer
Richard W
RW
Price
D051997:ADP-ribosyl Cyclase 1 / Q000378:metabolism; D044966:Anti-Retroviral Agents / Q000008:administration & dosage* / Q000276:immunology / Q000627:therapeutic use; D018791:CD4 Lymphocyte Count; D015496:CD4-Positive T-Lymphocytes / Q000378:metabolism; D018414:CD8-Positive T-Lymphocytes / Q000378:metabolism; D005260:Female; D015658:HIV Infections / Q000097:blood / Q000134:cerebrospinal fluid* / Q000188:drug therapy* / Q000276:immunology; D015497:HIV-1; D006684:HLA-DR Antigens / Q000378:metabolism; D006801:Humans; D008297:Male; D008875:Middle Aged; D019798:Neopterin / Q000097:blood / Q000134:cerebrospinal fluid; D010865:Pilot Projects; D011760:Pyrrolidinones / Q000008:administration & dosage* / Q000276:immunology / Q000627:therapeutic use; D012367:RNA, Viral / Q000097:blood / Q000134:cerebrospinal fluid*; D000068898:Raltegravir Potassium; D019713:Receptors, CCR5 / Q000378:metabolism
D044966:Anti-Retroviral Agents; D006684:HLA-DR Antigens; D011760:Pyrrolidinones; D012367:RNA, Viral; D019713:Receptors, CCR5; D000068898:Raltegravir Potassium; D019798:Neopterin; D051997:ADP-ribosyl Cyclase 1