HIV-1 is one of the most genetically diverse pathogens on earth. In fact, some coding regions, such as envelope, can have more than 30% genetic difference between clades. The neurocognitive effects of clade B HIV-1 infection have been well characterized in the developed world;however, there continues to be controversy surronding the effect of non-clade B infection on the neurocognitive functioning. The overarching aims of the proposed study is to 1) characterize and compare the burden of HIV associated neurocognitive disorders (HAND) occurring among individuals living in Brazil, China, India, Romania and the United States and infected with CRF01_AE and clades B, C and F, and 2) evaluate the neurovirulent and neurotropic genotypic determinants between subtypes. Important research questions that remain unanswered include: How do the prevalence, nature and course of HAND in various parts of the world compare when analyzed by population and subtype? What specific viral genetic characteristics are associated with neurovirulence and seeding of the central nervous system (CNS)? The current proposal is designed to systematically address these issues by: 1) determining the differential effect of HIV subtype on neurocognitive performance by measuring HAND using standardized measures in previously established cohorts in Brazil (clades B and C), China (CRF01_AE and clades B and C), India (clade C), Romania (clade F) and the United States (clade B), 2) determining viral genetic motifs from HIV RNA that are conserved during HAND by subtype and by study population by performing clade-typing of study participants by generating population based sequences of the env and tat coding regions from HIV RNA and DNA extracted from blood, and 3) determining viral genetic motifs from HIV RNA that are conserved during CNS compartmentalization between clades B and C by performing clonal sequencing of the env and tat coding regions from HIV RNA extracted from paired blood and CSF samples collected from participants with clade B or C infection in Brazil, India and the United States. The comparison of the burden of HAND between groups infected with different HIV clades requires standardized procedures for the measurement of HAND within and across populations. Investigations into clade-specific genotypic determinants of HIV neuropathogenesis and neurotropism requires: 1) well-characterized study populations and biologic samples from study participants, 2) standardization of measurements of neurocognitive functioning, 3) high quality HIV RNA sequencing capability in all research study settings, 4) secure and reliable data management and communication capabilities for sequence and study data between participating sites, and 5) expertise in state-of- the-art genotypic analysis. Our group has demonstrated experience in each of these areas.

Agency
National Institute of Health (NIH)
Institute
National Institute of Mental Health (NIMH)
Type
Research Project (R01)
Project #
5R01MH083552-05
Application #
8311774
Study Section
Special Emphasis Panel (ZMH1-ERB-S (02))
Program Officer
Joseph, Jeymohan
Project Start
2008-09-08
Project End
2014-08-31
Budget Start
2012-09-01
Budget End
2014-08-31
Support Year
5
Fiscal Year
2012
Total Cost
$654,066
Indirect Cost
$203,157
Name
University of California San Diego
Department
Internal Medicine/Medicine
Type
Schools of Medicine
DUNS #
804355790
City
La Jolla
State
CA
Country
United States
Zip Code
92093
Hu, Yihong; Wan, Zhenzhou; Zhou, Yan-Heng et al. (2017) Identification of Two New HIV-1 Circulating Recombinant Forms (CRF87_cpx and CRF88_BC) from Reported Unique Recombinant Forms in Asia. AIDS Res Hum Retroviruses 33:353-358
Osorio, Georgina; Hoenigl, Martin; Quartarolo, Jennifer et al. (2017) Evaluation of opt-out inpatient HIV screening at an urban teaching hospital. AIDS Care 29:1014-1018
Chen, Xin; Ye, Mei; Duo, Lin et al. (2017) First description of two new HIV-1 recombinant forms CRF82_cpx and CRF83_cpx among drug users in Northern Myanmar. Virulence 8:497-503
Obermeit, Lisa C; Beltran, Jessica; Casaletto, Kaitlin B et al. (2017) Evaluating the accuracy of self-report for the diagnosis of HIV-associated neurocognitive disorder (HAND): defining ""symptomatic"" versus ""asymptomatic"" HAND. J Neurovirol 23:67-78
de Almeida, Sergio M; Rotta, Indianara; Ribeiro, Clea E et al. (2017) Dynamic of CSF and serum biomarkers in HIV-1 subtype C encephalitis with CNS genetic compartmentalization-case study. J Neurovirol 23:460-473
Vanpouille, Christophe; Introini, Andrea; Morris, Sheldon R et al. (2016) Distinct cytokine/chemokine network in semen and blood characterize different stages of HIV infection. AIDS 30:193-201
de Almeida, Sergio M; Rotta, Indianara; Jiang, Yanxin et al. (2016) Biomarkers of chemotaxis and inflammation in cerebrospinal fluid and serum in individuals with HIV-1 subtype C versus B. J Neurovirol 22:715-724
Gianella, Sara; Ginocchio, Christine C; Daar, Eric S et al. (2016) Genital Epstein Barr Virus is associated with higher prevalence and persistence of anal human papillomavirus in HIV-infected men on antiretroviral therapy. BMC Infect Dis 16:24
Karris, Maile Y; Umlauf, Anya; Vaida, Florin et al. (2016) A randomized controlled clinical trial on the impact of CCR5 blockade with maraviroc in early infection on T-cell dynamics. Medicine (Baltimore) 95:e5315
Choi, Jun Yong; Chaillon, Antoine; Oh, Jin Ok et al. (2016) HIV migration between blood plasma and cellular subsets before and after HIV therapy. J Med Virol 88:606-13

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