Translational Medical Research Commons^™

Human Immunodeficiency Virus Type-1 (Hiv-1) Transcriptional Regulation, Latency And Therapy In The Central Nervous System, Joseph Hokello, Adhikarimayum Lakhikumar Sharma, Priya Tyagi, Alok Bhushan, Mudit Tyagi

College of Pharmacy Faculty Papers

The central nervous system (CNS) is highly compartmentalized and serves as a specific site of human immunodeficiency virus (HIV) infection. Therefore, an understanding of the cellular populations that are infected by HIV or that harbor latent HIV proviruses is imperative in the attempts to address cure strategies, taking into account that HIV infection and latency in the CNS may differ considerably from those in the periphery. HIV replication in the CNS is reported to persist despite prolonged combination antiretroviral therapy due to the inability of the current antiretroviral drugs to penetrate and cross the blood–brain barrier. Consequently, as a result …

Circumcision As An Intervening Strategy Against Hiv Acquisition In The Male Genital Tract, Adhikarimayum Lakhikumar Sharma, Joseph Hokello, Mudit Tyagi

Center for Translational Medicine Faculty Papers

Unsafe sex with HIV-infected individuals remains a major route for HIV transmission, and protective strategies, such as the distribution of free condoms and pre-or post-prophylaxis medication, have failed to control the spread of HIV, particularly in resource-limited settings and high HIV prevalence areas. An additional key strategy for HIV prevention is voluntary male circumcision (MC). International health organizations (e.g., the World Health Organization, UNAIDS) have recommended this strategy on a larger scale, however, there is a general lack of public understanding about how MC effectively protects against HIV infection. This review aims to discuss the acquisition of HIV through the …

An Update On The Hiv Dna Vaccine Strategy, Joseph Hokello, Adhikarimayum Lakhikumar Sharma, Mudit Tyagi

Center for Translational Medicine Faculty Papers

In 2020, the global prevalence of human immunodeficiency virus (HIV) infection was estimated to be 38 million, and a total of 690,000 people died from acquired immunodeficiency syndrome (AIDS)–related complications. Notably, around 12.6 million people living with HIIV/AIDS did not have access to life-saving treatment. The advent of the highly active antiretroviral therapy (HAART) in the mid-1990s remarkably enhanced the life expectancy of people living with HIV/AIDS as a result of improved immune functions. However, HAART has several drawbacks, especially when it is not used properly, including a high risk for the development of drug resistance, as well as undesirable …

Shedding Light On The Role Of Extracellular Vesicles In Hiv Infection And Wound Healing., Aseel Alqatawni, Adhikarimayum Lakhikumar Sharma, Beatrice Attilus, Mudit Tyagi, Rene Daniel

Center for Translational Medicine Faculty Papers

Extracellular vesicles (EVs) play an important role in intercellular communication. They are naturally released from cells into the extracellular environment. Based on their biogenesis, release pathways, size, content, and function, EVs are classified into exosomes, microvesicles (MVs), and apoptotic bodies (ApoBDs). Previous research has documented that EVs, specifically exosomes and MVs, play an important role in HIV infection, either by promoting HIV infection and pathogenesis or by inhibiting HIV-1 to a certain extent. We have also previously reported that EVs (particularly exosomes) from vaginal fluids inhibit HIV at the post-entry step (i.e., reverse transcription, integration). Besides the role that EVs …

Dna Dependent Protein Kinase (Dna-Pk) Enhances Hiv Transcription By Promoting Rna Polymerase Ii Activity And Recruitment Of Transcription Machinery At Hiv Ltr., Sonia Zicari, Adhikarimayum Lakhikumar Sharma, Geetaram Sahu, Larisa Dubrovsky, Lin Sun, Han Yue, Tejaswi Jada, Alex Ochem, Gary Simon, Michael Bukrinsky, Mudit Tyagi

Center for Translational Medicine Faculty Papers

Despite reductions in mortality from the use of highly active antiretroviral therapy (HAART), the presence of latent or transcriptionally silent proviruses prevents HIV cure/eradication. We have previously reported that DNA-dependent protein kinase (DNA-PK) facilitates HIV transcription by interacting with the RNA polymerase II (RNAP II) complex recruited at HIV LTR. In this study, using different cell lines and peripheral blood mononuclear cells (PBMCs) of HIV-infected patients, we found that DNA-PK stimulates HIV transcription at several stages, including initiation, pause-release and elongation. We are reporting for the first time that DNA-PK increases phosphorylation of RNAP II C-terminal domain (CTD) at serine …

Prevalence Of Asymptomatic Gonorrhea And Chlamydia Infections Among Ryan White Hiv Population Visiting A Center City Hiv Clinic, Sarah Stuccio, Rakhshanda Akram, Lisa A. Spacek

Phase 1

Introduction: Sexually transmitted infections (STIs) are a major public health problem. Two factors make their diagnosis challenging: frequent asymptomatic presentation and lack of screening, especially at extragenital sites. Additionally, STIs including gonorrhea (GC) and chlamydia (CT) have been shown to increase the risk of sexual HIV transmission. Information about the prevalence, as well as predictors of test positivity, of GC and CT infections can stress the importance of universal screening.

Methods: We carried out a retrospective analysis of the STI screening of patients who attended the Ryan White HIV clinic at Jefferson between 2016 and 2018. The primary …