Neurological Response to cART vs. cART plus Integrase Inhibitor and CCR5 Antagonist Initiated during Acute HIV

November Neurological Response to cART vs. cART plus Integrase Inhibitor and CCR5 Antagonist Initiated during Acute HIV Victor G. Valcour 0 1 2 3 Serena S. Spudich 0 1 2 3 Napapon Sailasuta 0 1 2 3 Nittaya Phanuphak 0 1 2 3 Sukalaya Lerdlum 0 1 2 3 James L. K. Fletcher 0 1 2 3 Eugene D. M. B. Kroon 0 1 2 3 Linda L. Jagodzinski 0 1 2 3 Isabel E. Allen 0 1 2 3 Collin L. Adams 0 1 2 3 Peeriya Prueksakaew 0 1 2 3 Bonnie M. Slike 0 1 2 3 Joanna M. Hellmuth 0 1 2 3 Jerome H. Kim 0 1 2 3 Jintanat Ananworanich 0 1 2 3 SEARCH 0 1 2 3 /RV 0 1 2 3 Study Group 0 1 2 3 0 Funding: This work is supported by R21MH086341 from the National Institutes of Health (VV), R01MH095613 from the National Institutes of Health (VV & SS), and a cooperative agreement (W81XWH- 07-2-0067) between the Henry M. Jackson Foundation for the Advancement of Military Medicine, Inc., and the U.S. Department of Defense (DoD) which includes support from the National Institutes of Mental Health. The views expressed are those of the authors and should not be construed to represent the 1 Data Availability Statement: All relevant data are within the paper and its Supporting Information files 2 Editor: Jon M. Jacobs, Pacific Northwest National Laboratory, UNITED STATES 3 1 Department of Neurology, University of California San Francisco , San Francisco , California, United States of America, 2 Department of Neurology, Yale University , New Haven , Connecticut, United States of America, 3 Huntington Medical Research Institutes, Pasadena, California, United States of America , 4 South East Asia Research Collaboration with Hawaii , The Thai Red Cross AIDS Research Centre, Bangkok, Thailand, 5 Faculty of Medicine, Chulalongkorn University , Bangkok , Thailand , 6 Department of Retrovirology, Armed Forces Research Institute of Medical Sciences, United States Component, Bangkok, Thailand, 7 United States Military HIV Research Program, Walter Reed Army Institute of Research, Silver Spring, Maryland, United States of America, 8 Department of Biostatistics and Epidemiology, University of California San Francisco , San Francisco , California, United States of America, 9 Henry M. Jackson Foundation for the Advancement of Military Medicine , Bethesda, Maryland , United States of America To compare central nervous system (CNS) outcomes in participants treated during acute HIV infection with standard combination antiretroviral therapy (cART) vs. cART plus integrase inhibitor and CCR5 antagonist (cART+). 24-week randomized open-label prospective evaluation. Participants were evaluated then randomized to initiate cART (efavirenz, tenofovir, and either emtricitabine or lamivudine) vs. cART+ (cART plus raltegravir and maraviroc) during acute HIV and re-evaluated at 4, 12 and 24 weeks. We examined plasma and CSF cytokines, HIV RNA levels, neurological and neuropsychological findings, and brain MRS across groups and compared to healthy controls. At baseline, 62 participants were in Fiebig stages I-V. Randomized groups were similar for mean age (27 vs. 25, p = 0.137), gender (each 94% male), plasma log10 HIV RNA (5.4 vs. - ¶ Membership of the SEARCH 010/RV 254 Study Group is provided in the Acknowledgments. * positions of the US Army or the Department of Defense or views of the National Institutes of Health. The authors received additional funding from the Intramural research programs of the National Institute of Allergy and Infectious Diseases and of the Vaccine and Gene Therapy Institute. The Thai Government Pharmaceutical Organization (tenofovir, lamivudine, efavirenz), Gilead (Truvada, Atripla), Merck (Sustiva, Isentress), and ViiV Healthcare (Selzentry) provided antiretroviral therapy. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. Competing Interests: Dr. Valcour has recently served as a consultant to ViiV Healthcare, who have supported antiretrovirals for this study but have not had input on the analyses or the manuscript. The authors also note that The Thai Government Pharmaceutical Organization (tenofovir, lamivudine, efavirenz), Gilead (Truvada, Atripla), Merck (Sustiva, Isentress), and ViiV Healthcare (Selzentry) provided antiretroviral therapy. This does not alter the authors' adherence to PLOS ONE policies on sharing data and materials. 5.6, p = 0.382), CSF log10 HIV RNA (2.35 vs. 3.31, p = 0.561), and estimated duration of HIV (18 vs. 17 days, p = 0.546). Randomized arms did not differ at 24 weeks by any CNS outcome. Combining arms, all measures concurrent with antiretroviral treatment improved, for example, neuropsychological testing (mean NPZ-4 of -0.408 vs. 0.245, p<0.001) and inflammatory markers by MRS (e.g. mean frontal white matter (FWM) choline of 2.92 vs. 2.84, p = 0.045) at baseline and week 24, respectively. Plasma neopterin (p<0.001) and interferon gamma-induced protein 10 (IP-10) (p = 0.007) remained elevated in participants compared to controls but no statistically (...truncated)