TY - JOUR
T1 - Central nervous system viral invasion and inflammation during acute HIV infection
AU - Valcour, Victor
AU - Chalermchai, Thep
AU - Sailasuta, Napapon
AU - Marovich, Mary
AU - Lerdlum, Sukalaya
AU - Suttichom, Duanghathai
AU - Suwanwela, Nijasri C.
AU - Jagodzinski, Linda
AU - Michael, Nelson
AU - Spudich, Serena
AU - Van Griensven, Frits
AU - De Souza, Mark
AU - Kim, Jerome
AU - Ananworanich, Jintanat
N1 - Funding Information:
The RV254/SEARCH 010 Study Group includes the following individuals: from SEARCH/TRCARC/HIV-NAT, Praphan Phanuphak, Nittaya Phanuphak, James Fletcher, Nipat Teeratakulpisarn, Nitiya Chomchey, Somprartthana Rattanamanee, Pairoa Praihirunkit, Sasiwimol Ubolyam, and Suteeraporn Pinyakorn; from Chulalongkorn University, Rungsun Re-rknimitr, Wiriyaporn Ridtitid, and Mantana Pothisri; from AFRIMS, Alex-andra Schuetz, Rapee Trichavaroj, Vatcharain Assawadarachai, Yuwadee Phuangngern, Wiriya Rutvisuttinunt, Nantana Tantibul, Panadda Sawang-sinth, Bessara Nuntapinit, Siriwat Akapirat, Wanwarang Khobchit, Sakuna Suksawad, Ajchariyarat Sangdara, Kultida Poltavee, Hathairat Savadsuk, Suwittra Chaemchuen, Surat Jongrakthaitae, Chayada Sajiaweerawan, Ni-pattra Tragonlugsana, Putida Saetun, Joseph Chiu, Robert Paris, and Viseth Ngauy; from the Thailand Ministry of Public Health–US Centers for Disease Control and Prevention Collaboration, Phunlerd Phyaraj, Su-paporn Chaikummao, Anchalee Varangruat, Pikun Luechai, Jaray Thong-tojay, Anuwat Sriporn, and Wipas Wimonsate; from UCSF, Stephanie Chiao, Edgar Busovaca, and Lauren Wendelken; from UH, Cecilia Shikuma; from the Military HIV Research Program, Jeff Currier, Sodsai Tovanabutra, Merlin Robb, Bonnie Slike, Sheila Peel, Ying Liu, and Silvia Ratto-Kim; from the US National Institutes of Allergy and Infectious Diseases (NIAID), Irini Sereti and Jessica Hodge; from the US National Cancer Institute: Frank Maldarelli, Mary Kearney, and Ann Wiggins; from SAIC-Frederic: Jacob Estes, Robin Dewar, and Adam Rupert; from VGTI-Florida, Rafick Sekaly, Nicolas Chomont, and Claire Vandergeeten; and from Monogram Biosciences, Laura Napolitano, Molly Martell, Yolanda Lie, and the R&D and PDO groups (for technical assistance).
PY - 2012/7/15
Y1 - 2012/7/15
N2 - Background.Understanding the earliest central nervous system (CNS) events during human immunodeficiency virus (HIV) infection is crucial to knowledge of neuropathogenesis, but these have not previously been described in humans.Methods.Twenty individuals who had acute HIV infection (Fiebig stages I-IV), with average 15 days after exposure, underwent clinical neurological, cerebrospinal fluid (CSF), magnetic resonance imaging, and magnetic resonance spectroscopy (MRS) characterization.Results.HIV RNA was detected in the CSF from 15 of 18 subjects as early as 8 days after estimated HIV transmission. Undetectable CSF levels of HIV (in 3 of 18) was noted during Fiebig stages I, II, and III, with plasma HIV RNA levels of 285 651, 2321, and 81 978 copies/mL, respectively. On average, the CSF HIV RNA level was 2.42 log10 copies/mL lower than that in plasma. There were no cases in which the CSF HIV RNA level exceeded that in plasma. Headache was common during the acute retroviral syndrome (in 11 of 20 subjects), but no other neurological signs or symptoms were seen. Intrathecal immune activation was identified in some subjects with elevated CSF neopterin, monocyte chemotactic protein/CCL2, and interferon-induced protein 10/CXCL-10 levels. Brain inflammation was suggested by MRS.Conclusions.CSF HIV RNA was detectable in humans as early as 8 days after exposure. CNS inflammation was apparent by CSF analysis and MRS in some individuals during acute HIV infection.
AB - Background.Understanding the earliest central nervous system (CNS) events during human immunodeficiency virus (HIV) infection is crucial to knowledge of neuropathogenesis, but these have not previously been described in humans.Methods.Twenty individuals who had acute HIV infection (Fiebig stages I-IV), with average 15 days after exposure, underwent clinical neurological, cerebrospinal fluid (CSF), magnetic resonance imaging, and magnetic resonance spectroscopy (MRS) characterization.Results.HIV RNA was detected in the CSF from 15 of 18 subjects as early as 8 days after estimated HIV transmission. Undetectable CSF levels of HIV (in 3 of 18) was noted during Fiebig stages I, II, and III, with plasma HIV RNA levels of 285 651, 2321, and 81 978 copies/mL, respectively. On average, the CSF HIV RNA level was 2.42 log10 copies/mL lower than that in plasma. There were no cases in which the CSF HIV RNA level exceeded that in plasma. Headache was common during the acute retroviral syndrome (in 11 of 20 subjects), but no other neurological signs or symptoms were seen. Intrathecal immune activation was identified in some subjects with elevated CSF neopterin, monocyte chemotactic protein/CCL2, and interferon-induced protein 10/CXCL-10 levels. Brain inflammation was suggested by MRS.Conclusions.CSF HIV RNA was detectable in humans as early as 8 days after exposure. CNS inflammation was apparent by CSF analysis and MRS in some individuals during acute HIV infection.
UR - http://www.scopus.com/inward/record.url?scp=84862885694&partnerID=8YFLogxK
U2 - 10.1093/infdis/jis326
DO - 10.1093/infdis/jis326
M3 - Article
C2 - 22551810
AN - SCOPUS:84862885694
SN - 0022-1899
VL - 206
SP - 275
EP - 282
JO - Journal of Infectious Diseases
JF - Journal of Infectious Diseases
IS - 2
ER -