• Title/Summary/Keyword: HIV model

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HPV Infection and Cervical Abnormalities in HIV Positive Women in Different Regions of Brazil, a Middle-Income Country

  • Freitas, Beatriz C;Suehiro, Tamy T;Consolaro, Marcia EL;Silva, Vania RS
    • Asian Pacific Journal of Cancer Prevention
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    • v.16 no.18
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    • pp.8085-8091
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    • 2016
  • Human papillomavirus is a virus that is distributed worldwide, and persistent infection with high-risk genotypes (HR-HPV) is considered the most important factor for the development of squamous cell cervical carcinoma (SCC). However, by itself, it is not sufficient, and other factors may contribute to the onset and progression of lesions. For example, infection with other sexually transmitted diseases such as human immunodeficiency virus (HIV) may be a factor. Previous studies have shown the relationship between HPV infection and SCC development among HIV-infected women in many regions of the world, with great emphasis on low- and middle-income countries (LMICs). Brazil is considered a LMIC and has great disparities across different regions. The purpose of this review was to highlight the current knowledge about HPV infection and cervical abnormalities in HIV+ women in Brazil because this country is an ideal setting to evaluate HIV impact on SCC development and serves as model of LMICs and low-resource settings.

Interaction of HIV-1 Core p24 Antigen with Human Monocytic Cell Line THP1 Results in TNF-${\alpha}$ Dependent Secretion of Matrix Metalloproteinase-9

  • Sung, Ji-Hye;Yoo, Seung-Hee;Park, Hae-Kyung;Chong, Young-Hae
    • The Journal of the Korean Society for Microbiology
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    • v.35 no.1
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    • pp.9-18
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    • 2000
  • Immunological mechanisms involving the release of inflammatory factors by HIV-1 infected microglia in the brain have been implicated in the pathogenesis of HIV dementia (HIVD). Since the regulation of matrix metalloproteinases (MMPs) activity can be influenced by variety of inflammatory mediators, this study was undertaken to look for a correlation between the MMP-9 release and the production of TNF-${\alpha}$ in response to HIV-1 p24 in the human monocyte cell line THP-1 as a model for microglia. First, it was shown that HIV-l core p24 antigen induced THP-1 to secrete MMP-9 in a dose response manner while it elicited a little effect on MMP-2 release in human astroglial cell line T98G. Next, it was found that p24 induced THP-1 to secrete TNF-${\alpha}$ without prior differentiation into macrophages by phorbol myristate acetate (PMA) treatment. Furthermore, anti-TNF-${\alpha}$ neutralizing antibodies significantly blocked p24-induced MMP-9 release in a dose dependent manner. Our data indicate that p24 antigen induces monocytic MMP-9 release by triggering up-regulation of TNF-${\alpha}$ secretion.

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CD7-Specific Single Chain Antibody Mediated Delivery of siRNA to T Cells Inhibits HIV Replication in a Humanized Mouse Model

  • Ban, Hong-Seok;Kumar, Priti;Kim, Na-Hyun;Choi, Chang-Son;Shankar, Premlata;Lee, Sang-Kyung
    • Proceedings of the Microbiological Society of Korea Conference
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    • 2008.05a
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    • pp.62-64
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    • 2008
  • A major hurdle to the development of RNA interference as therapy for HIV infection is the delivery of siRNA to T lymphocytes which are difficult cells to transfect even in vitro. We have employed a single chain antibody to the pan T cell surface antigen CD7 was conjugated to an oligo-9-arginine peptide (scFvCD7-9R) for T cell-specific siRNA delivery in NOD/SCIDIL2${\gamma}$-/- mice reconstituted with human peripheral blood lymphocytes (Hu-PBL). Using a novel delivery, we first show that scFvCD7-9R efficiently delivered CD4 siRNA into human T cells in vitro. In vivo administration to Hu-PBL mice resulted in reduced levels of surface CD4 expression on T cells. Mice infected with HIV-1 and treated on a weekly basis with scFvCD7-9R-siRNA complexes targeting a combination of viral genes and the host coreceptor molecule CCR5 successfully maintained CD4/CD3 T cell ratios up to 4 weeks after infection in contrast to control mice that displayed a marked reduction in CD4 T cell numbers. p24 antigen levels were undetectable in 3 of the 4 protected mice. scFvCD7-9R/antiviral siRNA treatment also helped maintain CD4 T cell numbers with reduced plasma viral loads in Hu-PBL mice reconstituted with PBMC from donors seropositive for HIV, indicating that this method can contain viral replication even in established HIV infections. Our results show that scFvCD7-9R could be further developed as a potential therapeutic for HIV-1 infection.

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Social Worker's Physical・Social Distance for People Living with HIV/AIDS (사회복지 업무 종사자의 HIV/AIDS 감염인에 대한 신체적・사회적 거리감)

  • Rhee, Young Sun;Lee, In Jeong
    • Korean Journal of Health Education and Promotion
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    • v.30 no.5
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    • pp.177-188
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    • 2013
  • Objectives: The purpose of this study was to evaluate the feeling of distance of social work practitioners for people living with HIV/AIDS(PLWHA) and to identify related factors. Methods: A total of 409 data were collected as convenience sampling from social welfare service providers. Independent variables were socio-demographic data, AIDS related knowledge, authoritarian personality, prejudice for minority(handicapped, women, foreigner, old aged), cultural competency. Data were analyzed by t-test, ANOVA, multiple regression analysis were conducted. Results: Multiple regression model was developed by integrating the significant variables from univariate analysis. Significant factors of physical distance were social prejudice against handicapped, knowledge about AIDS and critical awareness/knowledge about other culture. And significant factors of social distance were social prejudice against handicapped, knowledge about AIDS, authoritarian personality, critical awareness/knowledge about other culture. At last, we found that social prejudice against handicapped was the biggest factor for physical distance and authoritarian personality was the biggest factor for social distance of social work practitioners. Conclusions: The area of social services for PLWHA have to be expanded. Physical and social distance of professionals to provide services to PLWHA and factors affecting it is necessary to continue research. In addition, on the basis of these findings, specific training programs is need to be developed.

Characterization of Binding Mode of the Heterobiaryl gp120 Inhibitor in HIV-1 Entry: A Molecular Docking and Dynamics Simulation Study

  • Gadhe, Changdev G.;Kothandan, Gugan;Cho, Seung Joo
    • Bulletin of the Korean Chemical Society
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    • v.34 no.8
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    • pp.2466-2472
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    • 2013
  • Human immunodeficiency virus type-1 (HIV-1) is a causative agent of Acquired immunodeficiency syndrome (AIDS), which has affected a large population of the world. Viral envelope glycoprotein (gp120) is an intrinsic protein for HIV-1 to enter into human host cells. Molecular docking guided molecular dynamics (MD) simulation was performed to explore the interaction mechanism of heterobiaryl derivative with gp120. MD simulation result of inhibitor-gp120 complex demonstrated stability. Our MD simulation results are consistent with most of the previous mutational and modeling studies. Inhibitor has an interaction with the CD4 binding region. Van der Waals interaction between inhibitor and Val255, Thr257, Asn425, Met426 and Trp427 were important. This preliminary MD model could be useful in exploiting heterobiaryl-gp120 interaction in greater detail, and will likely to shed lights for further utilization in the development of more potent inhibitors.

The influence of infection ratio on Gradual Reduction of Drug Dose for the treatment of AIDS patients (AIDS환자 치료를 위한 점진적 약물감소기법에 감염속도상수가 미치는 영향)

  • Lee, Kang-Hyun;Jo, Nam-Hoon
    • The Transactions of The Korean Institute of Electrical Engineers
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    • v.56 no.1
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    • pp.174-182
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    • 2007
  • In this paper, we study the influence of infection ratio on gradual reduction of drug dose for the five state HIV infection model that explicitly includes the population of the virus. We first compute all equilibrium points of the model and investigate the stabilities of them. As a result, a bifurcation diagram is obtained which shows a change in the equilibrium points, or in their stability properties, as the drug effect $\eta$ is varied from 0 to 1(alternatively, drug dose is changed from 1 to 0). Based on the bifurcation diagram, we show that the gradual reduction of drug dose can be applied for the treatment of AIDS patients. Moreover, we analyze the influence of the variation of infection ratio on the gradual reduction treatment. Computer simulation results are also presented to validate the proposed results.

Investigation of the Protonated State of HIV-1 Protease Active Site

  • Nam, Ky-Youb;Chang, Byung-Ha;Han, Cheol-Kyu;Ahn, Soon-Kil;No, Kyoung-Tai
    • Bulletin of the Korean Chemical Society
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    • v.24 no.6
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    • pp.817-823
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    • 2003
  • We have performed ab initio calculation on the active site of HIV-1 protease. The FEP method was used to determine the binding free energy of four different of protonated states of HIV-1 protease with inhibitor. The structure of the active site and hole structure was taken from the X-ray crystallographic coordinates of the C₂ symmetric inhibitor A74704 protease bound. The active site was modeled with the fragment molecules of binding pocket, acetic acid/ acetate anion (Asp25, Asp125), formamide (amide bond of Thr26/Gly27, Thr126/ Gly127), and methanol as inhibitor fragment. All possibly protonated states of the active site were considered, which were diprotonated state (0, 0), monoprotonated (-1, 0),(0, -1) and diunprotonated state (-1, -1). Once the binding energy Debind, of each model was calculated, more probabilistic protonated states can be proposed from binding energy. From ab-initio results, the FEP simulations were performed for the three following mutations: Ⅰ) Asp25 … Asp125 → AspH25 … Asp125, ⅱ) Asp25 … Asp125 → Asp25 … AspH125, ⅲ) AspH25 … Asp125 → AspH25 … AspH125. The free energy difference between the four states gives the information of the more realistic protonated state of active site aspartic acid. These results provide a theoretical prediction of the protonation state of the catalytic aspartic residues for A74707 complex, and may be useful for the evaluation of potential therapeutic targets.

Factors Associated With Long-term Retention in Antiretroviral Therapy Among People Living With HIV: Evidence From a Tertiary Hospital in Jakarta, Indonesia

  • Ifael Yerosias Mauleti;Krishna Adi Wibisana;Djati Prasetio Syamsuridzal;Sri Mulyati;Vivi Lisdawati;Ika Saptarini;Nurhayati;Armedy Ronny Hasugian;Harimat Hendarwan
    • Journal of Preventive Medicine and Public Health
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    • v.57 no.3
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    • pp.252-259
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    • 2024
  • Objectives: This study investigated factors associated with the retention of people living with human immunodeficiency virus (HIV) on antiretroviral therapy (ART) during the first 3 years of treatment. Methods: A retrospective study using electronic health records was conducted at a tertiary hospital in Jakarta, Indonesia. Adult HIV-positive patients who started ART from 2010 until 2020 were included. A binary logistic regression model was used to identify factors associated with ART retention in the first 3 years. Results: In total, 535 respondents were included in the analysis. The ART retention rates for the first, second, and third years were 83.7%, 79.1%, and 77.2%, respectively. The multivariate analysis revealed a negative association between CD4 count when starting ART and retention. Patients with CD4 counts >200 cells/mL were 0.65 times less likely to have good retention than those with CD4 counts ≤200 cells/mL. The year of starting ART was also significantly associated with retention. Patients who started ART in 2010-2013 or 2014-2016 were less likely to have good retention than those who started ART in 2017-2020, with adjusted odds ratios of 0.52 and 0.40, respectively. Patients who received efavirenz-based therapy were 1.69 times more likely to have good retention than those who received nevirapine (95% confidence interval, 1.05 to 2.72). Conclusions: Our study revealed a decline in ART retention in the third year. The CD4 count, year of enrollment, and an efavirenz-based regimen were significantly associated with retention. Patient engagement has long been a priority in HIV programs, with interventions being implemented to address this issue.

Regression analysis of doubly censored failure time data with frailty time data with frailty

  • Kim Yang-Jin
    • Proceedings of the Korean Statistical Society Conference
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    • 2004.11a
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    • pp.243-248
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    • 2004
  • The timings of two successive events of interest may not be measurable, instead it may be right censored or interval censored; this data structure is called doubly censored data. In the study of HIV, two such events are the infection with HIV and the onset of AIDS. These data have been analyzed by authors under the assumption that infection time and induction time are independent. This paper investigates the regression problem when two events arc modeled to allow the presence of a possible relation between two events as well as a subject-specific effect. We derive the estimation procedure based on Goetghebeur and Ryan's (2000) piecewise exponential model and Gauss-Hermite integration is applied in the EM algorithm. Simulation studies are performed to investigate the small-sample properties and the method is applied to a set of doubly censored data from an AIDS cohort study.

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