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Regional brain volumetric changes despite 2 years of treatment initiated during acute HIV infection

Year: 2019
Type: article
Abstract: OBJECTIVE: To assess changes in regional brain volumes after 24 months among individuals who initiated combination antiretroviral therapy (cART) within weeks of HIV exposure. DESIGN: Prospective cohort study of Thai participants in the earliest stages of HIV-1infection. METHODS: Thirty-four acutely HIV-infected individuals (AHI; Fiebig I-V) underwent brain magnetic resonance (MR) imaging and MR spectroscopy at 1.5 T and immediately initiated cART. Imaging was repeated at 24 months. Regional brain volumes were quantified using FreeSurfer's longitudinal pipeline. Voxel-wise analyses using tensor-based morphometry (TBM) were conducted to verify regional assessments. Baseline brain metabolite levels, blood and cerebrospinal fluid biomarkers assessed by ELISA, and peripheral blood monocyte phenotypes measured by flow cytometry were examined as predictors of significant volumetric change. RESULTS: Participants were 31 ± 8 years old. The estimated mean duration of infection at cART initiation was 15 days. Longitudinal analyses revealed reductions in volumes of putamen (P < 0.001) and caudate (P = 0.006). TBM confirmed significant atrophy in the putamen and caudate, and also in thalamic and hippocampal regions. In exploratory post-hoc analyses, higher baseline frequency of P-selectin glycoprotein ligand-1 (PSGL-1)-expressing total monocytes correlated with greater caudate volumetric decrease (ρ = 0.67, P = 0.017), whereas the baseline density of PSGL-1-expressing inflammatory (CD14CD16) monocytes correlated with putamen atrophy (ρ = 0.65, P = 0.022). CONCLUSION: Suppressive cART initiated during AHI may not prevent brain atrophy. Volumetric decrease appears greater than expected age-related decline, although examination of longitudinal change in demographically similar HIV-uninfected Thai individuals is needed. Mechanisms underlying progressive HIV-related atrophy may include early activation and enhanced adhesive and migratory capacity of circulating monocyte populations.
Source: AIDS
DOI: 10.1097/qad.0000000000002436
Authors: Kalpana J. Kallianpur, Neda Jahanshad, Napapon Sailasuta, Khunthalee Benjapornpong, Phillip Chan, Mantana Pothisri, Netsiri Dumrongpisutikul, Elizabeth Laws, Lishomwa C. Ndhlovu, Katherine M. Clifford, Robert Paul, Linda Jagodzinski, Shelly Krebs, Jintanat Ananworanich, Serena Spudich, Victor Valcour
Institutions: University of Hawaiʻi at Mānoa, University of Southern California, Thai Red Cross Society, Chulalongkorn University, University of California, San Francisco, University of Missouri–St. Louis, Walter Reed Army Institute of Research, Henry M. Jackson Foundation, Yale University
Language: English
Subfield: Virology
Open Access status: green
Funders: U.S. Department of Defense, U.S. Department of Health and Human Services, Henry M. Jackson Foundation, National Institutes of Health, National Institute of Mental Health, National Center for Advancing Translational Sciences, National Institute on Minority Health and Health Disparities
Awards: RCMI Multidisciplinary And Translational Research Infrastructure EXpansion (RAMAT, Midcareer Mentoring Award for Patient-Oriented Research in HIV and Cognition, G1546679804, G1589278233, Long-Term CNS Consequences of Treatment During Acute Infection, Impact of Treatment on Brain Integrity in the Earliest Stages of HIV Infection, Monocytes and HIV CNS Reservoirs in Super Acute HIV Infection, G4119534169, G5850682332, G6063997168, Central Nervous System Effects in Acute HIV Seroconversion, US MILITARY HIV RESEARCH, US MILITARY HUMAN IMMONODEFIECIENCY VIRUS (HIV) RESEARCH PROGRAM, Ola HAWAII, Yale Clinical and Translational Science Award
OpenAlex ID: W2985806931
FWCI: 2.383
Cites: 90
Cited by: 36
Related to: 10