TY - JOUR
T1 - Raltegravir treatment intensification does not alter cerebrospinal fluid hiv-1 infection or immunoactivation in subjects on suppressive therapy
AU - Dahl, Viktor
AU - Lee, Evelyn
AU - Peterson, Julia
AU - Spudich, Serena S.
AU - Leppla, Idris
AU - Sinclair, Elizabeth
AU - Fuchs, Dietmar
AU - Palmer, Sarah
AU - Price, Richard W.
N1 - Funding Information:
Potential conflicts of interest. R. W. P. has received funding from Merck to support this investigator-initiated research study and an honorarium from Abbott for a conference presentation. All other authors: No reported conflicts.
Funding Information:
Financial support. This work was supported by the National Institutes of Health (NIH) (R21MH083520), Merck & Co (IISP ID: 33054), Swedish Doctors against AIDS Foundation, Foundation for AIDS Research, the Wallenberg Foundation, and the National Center for Research Resources via the University of California, San Francisco Clinical and Translational Sciences Institute (UL1 RR024131). The contents are solely the responsibility of the authors and do not represent the official views of the NIH or other funding agencies.
PY - 2011/12/15
Y1 - 2011/12/15
N2 - 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.
AB - 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.
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U2 - 10.1093/infdis/jir667
DO - 10.1093/infdis/jir667
M3 - Article
C2 - 22021620
AN - SCOPUS:81055124940
SN - 0022-1899
VL - 204
SP - 1936
EP - 1945
JO - Journal of Infectious Diseases
JF - Journal of Infectious Diseases
IS - 12
ER -