Clinical Research Unit

• Integrase Inhibitor Use Associated with Weight Gain in Women and Incident Diabetes Mellitus.
• Efficacy of Tocilizumab in Patients Hospitalized with Covid-19
• Prevalence of strongyloidiasis and schistosomiasis among migrants: a systematic review and meta-analysis
• Immunological and Neurometabolite Changes Associated With Switch From Efavirenz to an Integrase Inhibitor

Real-World Clinical Insights and Inflammatory Mechanisms of Integrase Inhibitor Associated Excess Weight Gain

PI: Archana Asundi
Sponsor: Boston-Providence Center for AIDS Research Developmental Grant (P30-AI042853)
The purpose of this study is to investigate and characterize weight changes associated with integrase strand transfer inhibitor antiretroviral agents by following following anthropomorphic, metabolic and inflammatory changes in persons with HIV who have gained weight on integrase inhibitors and are switching off these agents due to this effect. This is an observational study where participants are monitored for a year after their switch with the option to undergo vibration-controlled transient elastography (Fibroscan) in additional traditional body composition measurements.  

HIV Aging of Immune Function

PI: Suryaram Gummuluru, Jennifer Cappione, Manish Sagar
Sponsor: NIA (R01AG060890)
The purpose of this study is to compare the aging of the immune system in people living with HIV to the general population. Among persons living with HIV, a persistent state of immune activation and inflammation accelerates the process of aging. This causes people living with HIV to have immune system defects common in older populations. These effects persist despite suppression of HIV with antiretroviral medications. 
We believe that advancing age and HIV synergistically promote residual HIV gene expression that acts as a persistent and potential stimuli of immune activation. In order to investigate this relationship, are collecting blood samples from young (under 35) and older (over 50) cohorts, both in people living  with and without HIV. 

Gamma Delta T-cells and Inflammation in HIV Infection and Normal Aging

PI: Jennifer Cappione
Sponsor: NIA (R01AG065050)
In persons living with HIV,  chronic inflammation is present even with undetectable viral loads, and such persons often present with co-morbidities associated with older age, including bone loss, cancers, stroke, cardiovascular disease, and dementia. In this application, we propose to test the hypothesis that gamma delta (γδ) T cells, a unique ‘innate-like’ T cell subset, exhibit hyper-inflammatory activity in the gastrointestinal tract of aviremic older persons living with and without HIV and this aberrant activation directly causes increased permeability of intestinal epithelium, leading to movement of GI microbial products and inflammatory γδ T cells into the circulation, which spurs and propagates systemic inflammation. Identification of the mechanisms driving increased intestinal permeability with aviremic HIV infection and normal aging is critical to develop novel therapeutic strategies to abrogate and/or prevent age-associated co-morbidities

Impact of Smoking and its Cessation on Systemic and Airway Immune Activation

PI: Nina Lin
Sponsor: NIDA (R01DA042685)
Smoking is a major and urgent public health issue, especially for those living with HIV. Understanding the pathways by which smoking interacts with HIV-induced immune dysfunction in the lungs is critical to address this urgent public health concern. This project studies the immunological effects of smoking and quitting on lung health, and the ensuing change in HIV disease progression. The purpose of this study is to learn how smoking affects the immune systems in people with HIV infection. We would like to know if HIV infected smokers who quit smoking have different responses in the lung and immune system from people who keep smoking.

The Effects of Opioid Use on HIV-1 Reservoir Dynamics: Opioids, HIV, and Translation Study (OPHION)

PI: Athe Tsibris and Nina Lin
Sponsor: NIDA (R61DA047038)
The objective of this study is to understand the effects of opioid use on HIV-1 latency. HIV latency is the residual virus remaining in people living with HIV, despite achieving HIV suppression via antiretroviral therapy. Although opioids have been shown to interact with HIV in laboratory experiments, we want to understand how opioids react with HIV in humans, and what health effects this may have. In order to achieve these objectives we are collecting blood samples from approximately 120 patients from the BMC community, including those actively injecting opioid drugs, those on methadone or suboxone for the treatment of OUD, patients prescribed opioid drugs by their doctors, as well as people living with HIV who use no opioids. 

RABIT: Rapid Bacterial Identification Study

PI: Nina Lin
Sponsor: Day Zero Diagnostics
Bloodstream infections are one of the leading causes of morbidity and mortality in the United States. Rapid diagnosis is critical for improving survival, with an 8% rise in mortality for every hour that appropriate antibiotic treatment is delayed. However, the newest assays still either depend on a positive blood culture to initially isolate pathogenic bacteria, which takes at least 12-36 hours and fails in as many as 50% of cases of severe sepsis, or assess a very limited panel of pathogens
This study will evaluate the efficacy of a novel microbial whole genome sequencing (WGS) technique relative to traditional culture for pathogen identification and antimicrobial resistance (AMR) determination.
 

Characterization of Systemic and Local Immune Responses to Chlamydia Antigens in Women to support Vaccine Antigen Selection (The Chlamydia Study)

PI: Nina Lin
Sponsor: In collaboration with Merck
The purpose of this study is to characterize the cellular and humoral immune responses to Chlamydia candidate antigens among women with protective immunity to Chlamydia vs. women susceptible for Chlamydia infection in order to support Chlamydia vaccine development. 

SOLAR (Switch Onto Long-Acting Regimen)

PI: Archana Asundi
Sponsor: ViiV
People living with HIV undergo lifelong treatment with antiretroviral therapy (ART), in the form of fixed-dose combination pills taken orally. Taking ART daily is essential to achieve viral suppression and prevent the emergence of resistance mutations. Patients living with HIV and their physicians have observed that total pill burden, dosing frequency, and safety concerns are significant barriers to consistently adhering to their dosing schedules. Drug resistant HIV eventually emerges in most patients who struggle with medication adherence. Our goal is to test whether a long-acting injectable combination of cabotegravir-rilpivirine is as effective as taking the same medication orally.
Patients participating in SOLAR will receive an injection of study mediation every two months (60 days), or they will remain on oral ART (Biktarvy) for the 12-month duration of the study. Patients chosen to receive the study medication will be offered a choice to begin with an oral study medication before proceeding to the injectable (oral lead-in), or they may choose to receive the injectable right away (direct to inject). 
During the study we will monitor participants to see if they maintain viral suppression, compare the efficacy and side effects of oral Biktarvy compared to the long-acting injectable, and assess participant satisfaction across both arms of the study. 

Human Mosquito Immune Crosstalk 
Strategic Timing of Antiretroviral Treatment (START)
Effects of Bictegravir-Emtricitabine-Tenofovir Alafenamide on Coronary Flow Reserve in Stable HIV Patients (B/F/TAF-CFR) - Pilot Study (PET)
Randomized Trial to Prevent Vascular Events in HIV – REPRIEVE
Cardiovascular Disease Risk In HIV-infected Women: Sex-Specific Mechanisms of Risk and Risk Reduction among REPRIEVE Trial Participants