(2011 – 2016) – Principal Investigator for IVN Simona Ruta MD, PhD

Aim: Evaluation of neurocognitive dysfunctions associated with HIV infection (HAND) and decoding of viral and genetic factors associated with HAND in long term survivors, parenteraly infected with HIV during early childhood

Partners

Coordinator: University of California, San Diego, USA – responsible: Cristian Achim, M.D, Ph.D, Professor, Psychiatry and Neuropathology, University of California, San Diego, USA
Partners for Romania: Institute of Virology Stefan S. Nicolau – responsible Prof. Dr. Simona Ruta, „Dr. Victor Babes” Hospital of Infectious Diseases : – responsible Dr. Luminita Ene

Working team: Simona Ruta, Aura Temereanca

Project financed by NIH, grant number 5R01MH094159-04

Implementation period: 2011 – 2016

Summary: HIV status was associated with a lower global neurocognitive performance (evaluated for 7 domains: verbal fluency, speed of information processing, executive functioning, learning, memory, attention/working, motor skills), compared to uninfected age and sex matched controls. Strikingly, we found no significant differences between patients with undetectable and those with low levels of viremia in term of neurocognitive and functional deficits, but participants carrying resistant viruses tended to be more frequently cognitively impaired compared with participants harboring wild-type HIV. No signs of virologic compartmentalization were observed based on CSF vs plasma viral load and on the profile of pol sequences.

We explored sex differences and markers for cognitive impairment, after controlling for age and education. An interaction between sex, HIV status, and cognitive functioning was found in the psychomotor domain for women, despite less advanced disease. We further identified biomarkers associated with HAND and demonstrated that plasma IP-10 level is a closer correlate of NCI in women with chronic HIV infection, compared to men. Testing for latent infections that can act as possible confounders for the neurocognitive dysfunctions revealed a latent infection with T. gondii in one third of the patients, who had a trend of increase in impairment rates infection and an association with worse performance globally, in memory, speed of information processing, verbal and learning domain. A protocol for the HIV env gene sequencing was optimized, in order to evaluate the tropism of the viral strains and to obtain preliminary sequences that would allow the detection of possible molecular signatures associated with neurotropism

Results:

Articles

1. Ene L, Marcotte TD, Umlauf A, Grancea C, Temereanca A, Bharti A, Achim CL, Letendre S, Ruta S. Latent toxoplasmosis is associated with neurocognitive impairment in young adults with and without chronic HIV infection. Journal of Neuroimmunology 2016, FI=2, 53
2. Aura Temereanca, Cristiana Oprea, Joel O. Wertheim, Irina Ianache, Emanoil Ceausu, Costin Cernescu, Sanjay R. Mehta, Simona Ruta. HIV transmission clusters among injecting drug users in Romania. Romanian Biotechnological Letters, 2017 Jan-Feb;22(1):12307-12315. PMID: 29213206; PMCID: PMC5713907 FI=0.404, revista  ISI Romania
3. Ene  L, Duiculescu  D; Tardei  G;  Ruta S; Smith  D; Mehta S; Letendre S; Achim C Hepatitis B virus compartmentalization in the cerebrospinal fluid of HIV-infected patients Clin Microbiol Infect. 2015, 21(4): 387.e5-8. doi: 10.1016/j.cmi.2014.11.012..PMID: 25658525; FI=5,768
4. Burlacu R, Umlauf A, Luca A, Gianella S, Radoi R, Ruta SM, Marcotte TD, Ene L, Achim CL. Sex-based differences in neurocognitive functioning in HIV-infected young adults. AIDS. 2018 Jan 14;32(2):217-225. doi: 10.1097/QAD.0000000000001687. PMID: 29112063; PMCID: PMC5736415.
5. Temereanca A, Ene L, Rosca A, Diaconu CC, Luca A, Burlacu R, Radoi R, Bulacu-Talnariu A, Marcotte TD, Achim CL, Ruta S. Neurocognitive Impairment in the Combined Antiretroviral Therapy Era in a Romanian Cohort of Young Adults with Chronic HIV Infection. AIDS Res Hum Retroviruses. 2020 May;36(5):367-372. doi: 10.1089/AID.2019.0132. Epub 2019 Oct 8. PMID: 31476875; PMCID: PMC7232656.

Communications at national/international congresses:

1. Aura Temereanca, Adelina Rosca, Luminita Ene, Benchawa Soontornniyomkij, Carmen Diaconu, Claudia Dita, Cristian Achim, Simona Ruta. IP10- a possible biomarker for the progression of HIV infection. Oral presentation. 8th National HIV/AIDS Congress and the 3rd Central European HIV Forum, 5-7 May 2016, Sibiu, Romania, published in BMC Infectious Diseases 16(S3), June 2016 DOI: 10.1186/s12879-016-1480-8, IF 2.690
2. Aura Temereanca, Luminita Ene, Adelina Rosca, Camelia Grancea, Claudia Dita, Carmen Diaconu, Cristian L. Achim, Simona Ruta. The effect of lamivudine- versus tenofovir-containing antiretroviral regimen on hepatitis B infection in a cohort of HIV infected long term survivors. Oral presentation. 2nd Central and Eastern European Meeting on Viral Hepatitis And Co-Infection With HIV, October 6-7, 2016, Bucharest, Romania
3. Adelina Rosca, Luminita Ene, Gabriela Anton, Aura Temereanca, Cristian Achim, Simona Ruta. miRNA-29a – a potential marker of neurocognitive impairment in HIV- infected patients. Poster. The 13th International Symposium on NeuroVirology, June 2-6, 2015, San Diego, California, USA.
4. Rosca Adelina, Diaconu Carmen, Ene Luminita, Soontornniyomkij Benchawa, Achim Cristian, Botezatu Anca, Anton Gabriela, Temereanca Aura, Ruta Simona. Relationship between miR-29a expression level and pro-inflammatory cytokines in HIV-1 infected patients. E-poster. ECCMID 25 Edition, April 25-28, 2015, Copenhagen, Denmark.
5. Ene L, Marcotte T, Grancea C, Temereanca A, Luca A, Bharti A, Umlauf A, Achim CL, Letendre S, Ruta SM.  Poster Session. Latent toxoplasmosis is associated with neurocognitive impairment in a cohort of young adults with chronic HIV infection from Romania.  ISNV 13^th Symposium, 2-6 June 2015, San Diego, California, USA
6. Simona Ruta. The cellular miRNA 29A expression as a potential marker for neurocognitive impairment in HIV infected patients.  ARROW 2015, 5-6 Octombrie 2015, Bucuresti, Romania