SEARCH
Observational Studies:
SEARCH 010 (RV254) is an observational study in Bangkok, Thailand, screening 30,000 prospective participants each year and typically identifying 30 with Acute HIV Infection (AHI) in this span of time. Participants are enrolled at the Anonymous Clinic of the Thai Red Cross AIDS Research Centre. The objective of SEARCH 010 is to describe clinical, immunological, and virological characteristics of persons with acute HIV infection, and to identify and follow volunteers who may be candidates for future HIV intervention or treatment protocols due to diagnosis during acute infection.
SEARCH 013 (RV 304) provides control data for comparison with SEARCH 010. Involving a variety of optional procedures, including lumbar puncture, lymph node and gut biopsy, and MRI/MRS/DTI, SEARCH 013 compares HIV-negative and chronic HIV-positive participants to the AHI cohort of SEARCH 010. In particular, the study strives to characterize the immunological landscapes of locations where viral reservoirs are established, including the gut mucosa and central nervous system (CNS).
SEARCH 013 (RV 304) provides control data for comparison with SEARCH 010. Involving a variety of optional procedures, including lumbar puncture, lymph node and gut biopsy, and MRI/MRS/DTI, SEARCH 013 compares HIV-negative and chronic HIV-positive participants to the AHI cohort of SEARCH 010. In particular, the study strives to characterize the immunological landscapes of locations where viral reservoirs are established, including the gut mucosa and central nervous system (CNS).
Interventional Studies:
RV 397 is a treatment interruption study, recruiting from SEARCH 010, that tests the efficacy of vaccine administration during Analytical Treatment Interruption (ATI). The study will enroll HIV-infected participants who initiated antiretroviral therapy (ART) within the first few weeks of infection and who have successfully suppressed viral load with ART for at least 2 years. As in all interruption studies, participants will be monitored frequently and put back on ART if rebound is detected.
RV 398 is a protocol designed to study the co-administration of a vaccine and ART during Acute HIV Infection (AHI). The vaccine in question is VRC01, a monoclonal antibody capable of neutralizing HIV-1 by recognizing the location on the viral protein gp120 which binds to the host t-cell’s CD4 receptor. This Phase I study examines the safety and impact of VRC01 (given in conjunction with conventional ART) on viral dynamics during AHI.
SEARCH 018 (RV408) examines the impact on the nervous system of administering an adjunctive anti-inflammatory therapy with ART during AHI. The study will investigate the effects of the anti-inflammatory agent, telmisartan, in reducing systemic immune activation and trafficking of activated and HIV-infected cells into the CNS.
SEARCH 022 is a treatment interruption study that tracks participants, who have been on ART for at least 2 years, during Analytical Treatment Interruption (ATI). As in all interruption studies, participants will be monitored frequently and put back on ART if rebound is detected.
SEARCH 025 (RV412) is a surveillance study for participants who have completed a treatment interruption study, recruiting from the interruption studies listed above. Participants not on ART at study start will be monitored closely and put back on ART if rebound is detected.
SEARCH 026 (RV424) is a treatment Interruption study designed to investigate the nervous system effects of co-administering a histone deacetylase (HDAC) inhibitor combined with other medications and ART, followed by ATI. The study will recruit participants who have been on ART for at least 42 weeks from SEARCH 010. As in all interruption studies, participants will be monitored frequently and put back on ART if rebound is detected.
RV 398 is a protocol designed to study the co-administration of a vaccine and ART during Acute HIV Infection (AHI). The vaccine in question is VRC01, a monoclonal antibody capable of neutralizing HIV-1 by recognizing the location on the viral protein gp120 which binds to the host t-cell’s CD4 receptor. This Phase I study examines the safety and impact of VRC01 (given in conjunction with conventional ART) on viral dynamics during AHI.
SEARCH 018 (RV408) examines the impact on the nervous system of administering an adjunctive anti-inflammatory therapy with ART during AHI. The study will investigate the effects of the anti-inflammatory agent, telmisartan, in reducing systemic immune activation and trafficking of activated and HIV-infected cells into the CNS.
SEARCH 022 is a treatment interruption study that tracks participants, who have been on ART for at least 2 years, during Analytical Treatment Interruption (ATI). As in all interruption studies, participants will be monitored frequently and put back on ART if rebound is detected.
SEARCH 025 (RV412) is a surveillance study for participants who have completed a treatment interruption study, recruiting from the interruption studies listed above. Participants not on ART at study start will be monitored closely and put back on ART if rebound is detected.
SEARCH 026 (RV424) is a treatment Interruption study designed to investigate the nervous system effects of co-administering a histone deacetylase (HDAC) inhibitor combined with other medications and ART, followed by ATI. The study will recruit participants who have been on ART for at least 42 weeks from SEARCH 010. As in all interruption studies, participants will be monitored frequently and put back on ART if rebound is detected.
COLLABORATORS
Armed Forces Research Institute of Medical Sciences (AFRIMS), Thailand and US
Chulalongkorn University, Bangkok, Thailand
Henry M. Jackson Foundation (HJF), Bethesda, MD
Southeast Asia Research Collaboration with Hawaii (SEARCH), Bangkok, Thailand
Thai Red Cross AIDS Research Centre (TRCARC), Bangkok, Thailand
University of California, San Francisco
University of Hawaii, Manoa
University of Missouri, St. Louis
University of North Carolina, Chapel Hill
U.S. Military HIV Research Program (MHRP), Bethesda, MD
Walter Reed Army Institute of Research (WRAIR), Rockville, MD
SPONSORS
National Institutes of Health, National Institute of Mental Health (NIMH), National Institute of Neurological Disorders and Stroke (NINDS)
SELECTED PUBLICATIONS (see Publications):
Acute Retroviral Syndrome is Associated with High Viral Burden, CD4 Depletion, and Immune Activation in Systemic and Tissue Compartments. Crowell TA, Colby DJ, Pinyakorn S, Fletcher JLK, Kroon E, Schuetz A, Krebs SJ, Slike BM, Leyre L, Chomont N, Jagodzinski LL, Sereti I, Utay NS, Dewar R, Rerknimitr R, Chomchey N, Trichavaroj R, Valcour VG, Spudich S, Michael NL, Robb ML, Phanuphak N, Ananworanich J; RV254/SEARCH010 Study Group. Clin Infect Dis. 2017 Dec 7.
Depression and Anxiety are Common in Acute HIV Infection and Associate with Plasma Immune Activation. Hellmuth J, Colby D, Valcour V, Suttichom D, Spudich S, Ananworanich J, Prueksakaew P, Sailasuta N, Allen I, Jagodzinski LL, Slike B, Ochi D, Paul R; RV254/SEARCH 010 Study Group. AIDS Behav. 2017 Nov;21(11):3238-3246.
Immediate initiation of cART is associated with lower levels of cerebrospinal fluid YKL-40, a marker of microglial activation, in HIV-1 infection. Peluso MJ, Valcour V, Phanuphak N, Ananworanich J, Fletcher JL, Chalermchai T, Krebs SJ, Robb ML, Hellmuth J, Gisslén M, Zetterberg H, Spudich S; RV254SEARCH 010, RV304SEARCH 013, and SEARCH 011 Study Teams. AIDS. 2017 Jan 14;31(2):247-252.
Neurologic signs and symptoms frequently manifest in acute HIV infection. Hellmuth J, Fletcher JL, Valcour V, Kroon E, Ananworanich J, Intasan J, Lerdlum S, Narvid J, Pothisri M, Allen I, Krebs SJ, Slike B, Prueksakaew P, Jagodzinski LL, Puttamaswin S, Phanuphak N, Spudich S; SEARCH 010/RV254 Study Group. Neurology. 2016 Jul 12;87(2):148-54.
Neurological Response to cART vs. cART plus Integrase Inhibitor and CCR5 Antagonist Initiated during Acute HIV. Valcour VG, Spudich SS, Sailasuta N, Phanuphak N, Lerdlum S, Fletcher JL, Kroon ED, Jagodzinski LL, Allen IE, Adams CL, Prueksakaew P, Slike BM, Hellmuth JM, Kim JH, Ananworanich J; SEARCH 010/RV 254 Study Group. PLoS One. 2015 Nov 10;10(11):e0142600.
Neuropsychological Impairment in Acute HIV and the Effect of Immediate Antiretroviral Therapy. Kore I, Ananworanich J, Valcour V, Fletcher JL, Chalermchai T, Paul R, Reynolds J, Tipsuk S, Ubolyam S, Rattanamanee S, Jagodzinski L, Kim J, Spudich S; RV254/SEARCH 010 Study Group. J Acquir Immune Defic Syndr. 2015 Dec 1;70(4):393-9.
Absence of Cerebrospinal Fluid Signs of Neuronal Injury Before and After Immediate Antiretroviral Therapy in Acute HIV Infection. Peluso MJ, Valcour V, Ananworanich J, Sithinamsuwan P, Chalermchai T, Fletcher JL, Lerdlum S, Chomchey N, Slike B, Sailasuta N, Gisslén M, Zetterberg H, Spudich S; RV254/SEARCH 010 and SEARCH 011 Study Teams. J Infect Dis. 2015 Dec 1;212(11):1759-67.
Change in brain magnetic resonance spectroscopy after treatment during acute HIV infection. Sailasuta N, Ross W, Ananworanich J, Chalermchai T, DeGruttola V, Lerdlum S, Pothisri M, Busovaca E, Ratto-Kim S, Jagodzinski L, Spudich S, Michael N, Kim JH, Valcour V; RV254/SEARCH 010 protocol teams. PLoS One. 2012;7(11):e49272.
Central nervous system viral invasion and inflammation during acute HIV infection. Valcour V, Chalermchai T, Sailasuta N, Marovich M, Lerdlum S, Suttichom D, Suwanwela NC, Jagodzinski L, Michael N, Spudich S, van Griensven F, de Souza M, Kim J, Ananworanich J; RV254/SEARCH 010 Study Group. J Infect Dis. 2012 Jul 15;206(2):275-82.
Armed Forces Research Institute of Medical Sciences (AFRIMS), Thailand and US
Chulalongkorn University, Bangkok, Thailand
Henry M. Jackson Foundation (HJF), Bethesda, MD
Southeast Asia Research Collaboration with Hawaii (SEARCH), Bangkok, Thailand
Thai Red Cross AIDS Research Centre (TRCARC), Bangkok, Thailand
University of California, San Francisco
University of Hawaii, Manoa
University of Missouri, St. Louis
University of North Carolina, Chapel Hill
U.S. Military HIV Research Program (MHRP), Bethesda, MD
Walter Reed Army Institute of Research (WRAIR), Rockville, MD
SPONSORS
National Institutes of Health, National Institute of Mental Health (NIMH), National Institute of Neurological Disorders and Stroke (NINDS)
- R01MH095613
- R01MH104141
- R01NS084911
SELECTED PUBLICATIONS (see Publications):
Acute Retroviral Syndrome is Associated with High Viral Burden, CD4 Depletion, and Immune Activation in Systemic and Tissue Compartments. Crowell TA, Colby DJ, Pinyakorn S, Fletcher JLK, Kroon E, Schuetz A, Krebs SJ, Slike BM, Leyre L, Chomont N, Jagodzinski LL, Sereti I, Utay NS, Dewar R, Rerknimitr R, Chomchey N, Trichavaroj R, Valcour VG, Spudich S, Michael NL, Robb ML, Phanuphak N, Ananworanich J; RV254/SEARCH010 Study Group. Clin Infect Dis. 2017 Dec 7.
Depression and Anxiety are Common in Acute HIV Infection and Associate with Plasma Immune Activation. Hellmuth J, Colby D, Valcour V, Suttichom D, Spudich S, Ananworanich J, Prueksakaew P, Sailasuta N, Allen I, Jagodzinski LL, Slike B, Ochi D, Paul R; RV254/SEARCH 010 Study Group. AIDS Behav. 2017 Nov;21(11):3238-3246.
Immediate initiation of cART is associated with lower levels of cerebrospinal fluid YKL-40, a marker of microglial activation, in HIV-1 infection. Peluso MJ, Valcour V, Phanuphak N, Ananworanich J, Fletcher JL, Chalermchai T, Krebs SJ, Robb ML, Hellmuth J, Gisslén M, Zetterberg H, Spudich S; RV254SEARCH 010, RV304SEARCH 013, and SEARCH 011 Study Teams. AIDS. 2017 Jan 14;31(2):247-252.
Neurologic signs and symptoms frequently manifest in acute HIV infection. Hellmuth J, Fletcher JL, Valcour V, Kroon E, Ananworanich J, Intasan J, Lerdlum S, Narvid J, Pothisri M, Allen I, Krebs SJ, Slike B, Prueksakaew P, Jagodzinski LL, Puttamaswin S, Phanuphak N, Spudich S; SEARCH 010/RV254 Study Group. Neurology. 2016 Jul 12;87(2):148-54.
Neurological Response to cART vs. cART plus Integrase Inhibitor and CCR5 Antagonist Initiated during Acute HIV. Valcour VG, Spudich SS, Sailasuta N, Phanuphak N, Lerdlum S, Fletcher JL, Kroon ED, Jagodzinski LL, Allen IE, Adams CL, Prueksakaew P, Slike BM, Hellmuth JM, Kim JH, Ananworanich J; SEARCH 010/RV 254 Study Group. PLoS One. 2015 Nov 10;10(11):e0142600.
Neuropsychological Impairment in Acute HIV and the Effect of Immediate Antiretroviral Therapy. Kore I, Ananworanich J, Valcour V, Fletcher JL, Chalermchai T, Paul R, Reynolds J, Tipsuk S, Ubolyam S, Rattanamanee S, Jagodzinski L, Kim J, Spudich S; RV254/SEARCH 010 Study Group. J Acquir Immune Defic Syndr. 2015 Dec 1;70(4):393-9.
Absence of Cerebrospinal Fluid Signs of Neuronal Injury Before and After Immediate Antiretroviral Therapy in Acute HIV Infection. Peluso MJ, Valcour V, Ananworanich J, Sithinamsuwan P, Chalermchai T, Fletcher JL, Lerdlum S, Chomchey N, Slike B, Sailasuta N, Gisslén M, Zetterberg H, Spudich S; RV254/SEARCH 010 and SEARCH 011 Study Teams. J Infect Dis. 2015 Dec 1;212(11):1759-67.
Change in brain magnetic resonance spectroscopy after treatment during acute HIV infection. Sailasuta N, Ross W, Ananworanich J, Chalermchai T, DeGruttola V, Lerdlum S, Pothisri M, Busovaca E, Ratto-Kim S, Jagodzinski L, Spudich S, Michael N, Kim JH, Valcour V; RV254/SEARCH 010 protocol teams. PLoS One. 2012;7(11):e49272.
Central nervous system viral invasion and inflammation during acute HIV infection. Valcour V, Chalermchai T, Sailasuta N, Marovich M, Lerdlum S, Suttichom D, Suwanwela NC, Jagodzinski L, Michael N, Spudich S, van Griensven F, de Souza M, Kim J, Ananworanich J; RV254/SEARCH 010 Study Group. J Infect Dis. 2012 Jul 15;206(2):275-82.